Pyrroloquinoline quinone - for energy issues

Laura

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I read about this stuff recently when surfing around about DNA regeneration processes. As we know, caloric restriction (keto diet) and intense exercise can trigger upregulation of wild mtDNA and reverse a lot of disease processes. So, I wondered if anyone else has read anything about it or tried it. It looks VERY interesting for all of those people who have energy issues or mtDNA problems.

In 2010, researchers at the University of California at Davis released a peer-reviewed publication showing that PQQ’s critical role in growth and development stems from its unique ability to activate cell signaling pathways directly involved in cellular energy metabolism, development, and function.

Most significantly, the study demonstrated that PQQ not only protects mitochondria from oxidative stress—it promotes the spontaneous generation of new mitochondria within aging cells, a process known as mitochondrial biogenesis. The implications of this discovery for human health and longevity are significant because the only other known methods proven to stimulate mitochondiral biogenesis in aging humans are intense aerobic exercise, strict caloric restriction, and certain medications such as thiazolidinediones and the diabetes drug metformin....


PQQ activates expression of PCG-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), a “master regulator” that mobilizes cells’ response to various external triggers. It directly stimulates genes that promote mitochondrial and cellular respiration, growth, and proliferation. Its capacity to upregulate cellular metabolism at the genetic level favorably affects blood pressure, cholesterol and triglyceride breakdown, and the onset of obesity.

PQQ triggers the CREB signaling protein (cAMP-response element-binding protein), which plays a pivotal role in embryonic development and growth. It also beneficially interacts with histones, proteins involved in the packaging and nuclear organization of cell DNA. CREB also stimulates the growth of new mitochondria.

PQQ regulates a recently discovered cell signaling protein called DJ-1. As with PCG-1α and CREB, DJ-1 is involved in cell function and survival, has been shown to prevent cell death by combating intensive oxidative stress, and is likely important to brain health and function. DJ-1 mutations have been conclusively linked to the onset of rare inherited forms of Parkinson’s disease and other neurological disorders. ...

PQQ is a neuroprotective compound that has been shown in a small number of preliminary studies to protect memory and cognition in aging animals and humans. It has been shown to reverse cognitive impairment caused by chronic oxidative stress in animal models and improve performance on memory tests. 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.

PQQ has also been shown to safeguard against the self-oxidation of the DJ-1 protein, an early step in the onset of some forms of Parkinson’s disease.

PQQ protects brain cells against oxidative damage following ischemia-reperfusion injury—the inflammation and oxidative damage that result from the sudden return of blood and nutrients to tissues deprived of them by stroke. Reactive nitrogen species (RNS) arise spontaneously following stroke and spinal cord injuries and impose severe stresses on damaged neurons, contributing to subsequent long-term neurological damage. PQQ suppresses RNS in experimentally induced strokes, and provides additional protection following spinal cord injury by blocking inducible nitric oxide synthase (iNOS), a major source of RNS. ...

PQQ also protects the brain against neurotoxicity induced by other powerful toxins, including mercury(a suspected factor in the development of Alzheimer’s disease) and oxidopamine (a potent neurotoxin used by scientists to induce Parkinsonism in laboratory animals by destroying dopaminergic and noradrenergic neurons.)

PQQ prevents aggregation of alpha-synuclein, a protein associated with Parkinson’s disease. PQQ also protects nerve cells from the toxic effects of the amyloid-beta protein linked with Alzheimer’s disease, and reduces the formation of new amyloid beta aggregates. ...

PQQ has been shown to promote memory, attention, and cognition in laboratory animals.

In humans, in one double-blind, placebo-controlled clinical trial conducted in Japan in 2007, supplementation with 20 mg per day of PQQ resulted in improvements on tests of higher cognitive function in a group of 71 middle-aged and elderly people aged between 40-70, who outperformed the placebo group by more than twofold in their standardized memory tests. Interestingly, co-administration of the unrelated compound coenzyme Q10 (CoQ10) further improved performance on standardized memory tests when subjects also took 300 mg per day of CoQ10. No adverse effects were linked to the supplementation, and the results suggested that PQQ, especially when combined with CoQ10, can be used to improve mental status and quality of life in older patients, and help slow or prevent age-related cognitive decline in middle-age patients....

Chowanadisai, W.; Bauerly, K. A.; Tchaparian, E.; Wong, A.; Cortopassi, G. A.; Rucker, R. B. (January 2010). "Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression". http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804159/

Lanza, I. R.; Sreekumaran Nair, K. (August 2010). "Regulation of skeletal muscle mitochondrial function: genes to proteins". Acta Physiologica 199 (4): 529–547.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070482/

All in all, it looks quite interesting.
 
I have found it on Iherb:

_http://www.iherb.com/Jarrow-Formulas-PQQ-Pyrroloquinoline-Quinone-20-mg-30-Capsules/48939#p=1&oos=1&disc=0&lc=en-US&w=Pyrroloquinoline%20quinone&rc=15&sr=null&ic=1

However, it seems a bit pricey.

This one seems better:

_http://www.iherb.com/Jarrow-Formulas-Ubiquinol-QH-PQQ-30-Softgels/49632#p=1&oos=1&disc=0&lc=en-US&w=Pyrroloquinoline%20quinone&rc=15&sr=null&ic=8
 
Dr. Jack Kruse, whose work we mostly know from the cold-acclimitization thread, put PQQ on his top ten list of supplements to take on a Paleo diet.

_http://www.jackkruse.com/what-are-the-top-ten-paleo-supplements/

Many Paleo folks may not even know what this is. I call it the long-sought-after “exercise in pill form.” PQQ is pyrroloquinoline quinone, and is probably the most important B vitamin when one is transitioning from a sugar burning metabolism (which is what the Standard American Diet creates) to a fat burning furnace (Paleo/Primal diet). When I first began to blog, I started with a deep mitochondrial series. I think many questioned why I did so: your change to a Paleo diet it is really not maximized unless your mitochondria are optimal first. This was shown in the leptin series, as well at the muscle level (Oprah post). In my practice, helping my patients become leptin sensitive is one of the first clinical moves I make to light the pilot light of the mitochondria.

PQQ has two major effects that make it critical: it’s stimulatory to mitochondrial biogenesis. If you read my mitochondrial series from June of 2011, you will see why this is critical to reengineer a human to optimal. Since I have written extensively about leptin, energy efficiency is critical to optimization. If one is energy deficient due to leptin resistance (hormone cascade disruption) or due to poor mitochondrial function (inability to make energy well), there is little chance of getting someone to optimal quickly. My Leptin Rx solves the steroid cascade problem. PQQ is the tuneup that the furnace needs. Remember, our mitochondria are the engines that drive our metabolisms. If one is devoid of energy, we call that person a cadaver. If one is lacking energy, they are either leptin resistant or the owner of a bunch of bad mitochondria. Most people on a the Standard American Diet have a Nissan Sentra engine in their Ferrari body. There is a huge energy mismatch of what their bodies want to do and what they can do. This obviously affects basic functions and the ability to exercise, too.

The second major effect of PQQ is glycation control from AGEs and ALEs. One of the under-appreciated benefits of going Paleo is the huge change in dietary carnosine intake. What is carnosine? Carnosine is a multifunctional dipeptide that interferes directly with the glycation process. Carnosine has been shown to inhibit glycation early on, thus helping protect us against further damage as we age. Carnosine is found in large amounts in red meat and seafoods. When one makes the change to Paleo, the substrate for electrons in our food is red, grass-fed meat/seafood loaded with carnosine. A person eating a Standard American Diet is filled with mitochondria not optimally equipped to handle an acute change to massive carnosine. Some other little known facts in our Paleo community about carnosine is that its levels fall off rather dramatically in humans as we age. It has also been shown in research that high levels of carnosine are also seen clinically in humans with long telomere lengths. Long telomere lengths indicate longevity.

Longer telomeres are directly tied to mitochondrial health and optimal functioning. This biology was worked out by Nobel Prize winner Elizabeth Blackburn’s lab at UCSF in 2009. Having great mitochondria is critical if you are going to make the superior substrate jump in a Paleo lifestyle. It makes no sense biologically to eat great if your body’s engine cannot harness that power to transform your health. I recommend a higher dose of PQQ for all Paleo patients: 20mgs a day. If I eat a lot of meat and coconut oil because I worked out hard, I will dose even higher.
 
I've seen it before on Amazon.co.UK : _http://www.amazon.co.uk/Life-Extension-Bio-pqq-Pyrroloquinoline-Quinone/dp/B0052HUR8Q

That's £35 for three bottles. And then there's this claim
Life Extension uses a purified, highly potent form of PQQ from Japan that is produced through a unique fermentation process. The result is BioPQQ®, the highest quality PQQ available on the market today.
_http://www.lef.org/Vitamins-Supplements/Item01500/PQQ-Caps-with-BioPQQ.html

Some info dotted around the web...

_http://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0018189#info=&term=ancchart here, an interactive chart might help with the voluminous information given in certain quarters. Just click any box for more.
PQQ Rich Foods

September 20, 2010 by Michael Rucker
Several have inquired about PQQ in food and whether diet alone is sufficient to obtain enough pyrroloquinoline quinone to be biologically effective. The answer, relative to what is known about optimizing growth in rodent nutritional growth experimental models, is probably yes. However, some rather broad assumptions have to be made, because of the limited amounts of data regarding the forms of PQQ in different foods.

For perspective, Dr. Steinberg out of the University of California Davis has presented data that suggests PQQ is needed at ~200-400 micrograms per kilogram of dry food. Given that most lactating mammals have the same vitamin and mineral requirements when the amounts are expressed on a food energy or dry food weight basis, for humans, who consume about 300 to 500 grams of dry food per day (about 2000 Kcal), one might infer that 100-200 micrograms of PQQ per day may be sufficient.

In the section, Pyrroloquinoline quinone and CoQ10, we previously discussed that pyrroloquinoline quinone exists as salts or as complex derivatives of amino acids, imidazolopyrroloquinolines, and abbreviated IPQs. For PQQ consumed in the diet (even as a supplement), much of it is converted to IPQ (Pyrroloquinoline Quinone Improves Growth and Reproductive Performance in Mice Fed Chemically Defined Diets). In human milk, the ratio of IPQ to PQQ was estimated to be about 8:1 (Characterization of Pyrroloquinoline Quinone Amino Acid Derivatives by Electrospray Ionization Mass Spectrometry and Detection in Human Milk). In foods, it id reported (Simple and Sensitive Method for Pyrroloquinoline Quinone (PQQ) Analysis in Various Foods Using Liquid Chromatography/Electrospray-Ionization Tandem Mass Spectrometry) that the ratio under their assay conditions may be closer to 2:1. Regrettably, tissue preparation, acidity or alkalinity, and temperature can impact and alter PQQ and IPQ values. For example, under alkaline conditions (above pH8) almost all pyrroloquinoline quinone is converted to derivatives when PQQ is introduced into a complex mixture or environment.

PQQ in Food *

PQQ in Food

* In addition to the values taken from published papers, some of the values are from conference reports or abstracts presented at meetings. As noted in the main text, there is a lot of variability. Kamazama et al. in their 1995 Biochemistry Journal paper report ~0.06 micrograms as the PQQ concentration in dried skim milk per 100 grams of milk solids. However, later in an abstract of a paper presented at the Biochemical Society Transactions in 2000 in England, they report detection and quantization of IPQ in human breast milk at 0.14 to 5.5 microgram/100 mL of fresh milk or 1.4 to 55 micrograms per 100 grams of milk solids. Given the variability, this is inline with the data reported in Characterization of Pyrroloquinoline Quinone Amino Acid Derivatives by Electrospray Ionization Mass Spectrometry and Detection in Human Milk, i.e. ~140-180 micrograms (PQQ +IPQ) per 100 g of milk solids. Moreover, Fluckinger et al. reported that the PQQ concentration of milk is 15-150 micrograms/100 mL or 150 to 500 micrograms/100 grams of bovine milk solids. For the Fluckinger assays PQQ was separated and then measured using a 16-channel electrochemical detector, a highly precise and sensitive procedure. All other assay involved sophisticated separation and mass spectrometer for detection, also highly precise and sensitive.

The information above is taken mostly from the work of Kumazawa et al. (Levels of pyrroloquinoline quinone in various foods). Some of the values are higher than corresponding values for foods analyzed by Noji et al. (Simple and Sensitive Method for Pyrroloquinoline Quinone (PQQ) Analysis in Various Foods Using Liquid Chromatography/Electrospray-Ionization Tandem Mass Spectrometry). Although the number of foods analyzed is small, an important finding is that PQQ has been observed in all tissues analyzed to date in both plants and animals.

In the above table, Column A indicates some of the currently available sources for pyrroloquinoline quinone (for which compositional values have been obtained). Column B are amounts taken mostly from the Kumazawa et al. paper, but are expressed as micrograms of PQQ per 100 grams of food (~1/4 lb) and not as nanograms per grams of food (as they were originally reported). Next, in column C, the amounts in column B are multiplied by 5-10 to obtain an estimate of micrograms of PQQ per 100 grams of dried foods or so-called food solids (e.g., given that most of the food items mentioned contain at least 75% water or more). Column D requires making some guesses.

As noted, some researchers have reported that IPQ is 5 to 8 times greater than the amount of PQQ in tissues. While others have reported a low ratio of 2 to 3 for IPQ to PQQ. Thus, the apparent IPQ + PQQ values given in Column D range from the lowest to highest amounts obtained by multiplying arbitrarily the values in Column C by 2 or 8. Column E is even trickier. It represents the estimated amounts consumed per day for an “ideal” person consuming a maintenance diet of 2000 calories per day. Regarding the diet consumed, the values for the major food categories are based on the estimated amounts consumed per day (on a dry weight basis) derived from values given in the USDA publication, Profiling Food Consumption in America. The question is whether a typical selection of foods can yield the minimum amount that corresponds to optimizing growth in animal models, i.e. about 100-200 microgram per day. If you’re curious about pyrroloquinoline quinone intake please visit PQQ Dosage, What size pyrroloquinoline quinone pills should I take?.

Regarding various conclusions, the first is that much better data are needed. However, setting aside that concern and assuming the actual values for PQQ in foods may be at the median (middle) of the estimates provided, one can guess that a typical intake in humans is indeed about 0.3 mg or 300 micrograms of pyrroloquinoline quinone per day or more. That amount is very much is line with the amount of pyrroloquinoline quinone or PQQ + IPQ needed to stimulate growth in animals. It is also an amount that is found in human milk, which is always a good starting point in assessing a need related to growth or maintenance.

So what can we conclude? In the paper by Kumazawa et al. Levels of pyrroloquinoline quinone in various foods it is stated that probably the PQQ in animal tissues are derived at least in part from the diet given and that the levels of pyrroloquinoline quinone in plant tissues are in the aggregate about 10 times those in animal tissues. In a review by Rucker et al. Potential physiological importance of pyrroloquinoline quinone, the same conclusion was reached, particularly given that stomach microflora does not make an abundance of PQQ . The data also beg the question do we need supplements and if so how much? Many of the PQQ products sold are in the 10-20 mg range. As indicated in the section — PQQ Dosage, What size pyrroloquinoline quinone pills should I take? — we discuss that the reasonable pyrroloquinoline quinone dosage, like many supplements, for an active adult is probably the result of an arbitrary decision, but the levels we’ve reported are safe and effective. From the inferences developed in this section, however, a 3-5 mg supplement per day may be sufficient and just as effective for an average health adult. Such dietary levels are more than sufficient to sustain optimal mitochondriogenesis in animal models. As a final point, unlike many dietary factors and biofactors, PQQ and its derivatives are sustained in tissues and seem to play a fundamental role related to energy metabolism. In this regard, the dosage might vary depending on your desired outcome.


- See more at: _http://www.functional-supplements.com/pqq-info/pqq-rich-food/#sthash.7ybwiDWO.dpuf

Since Kamazama was cited, here is the paper in question, on PubMed's database - link. _http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1136652/

The reports of those who have taken the supplement vary, some say eating several kilograms of natto (fermented) would be good to get PQQ, but that would be equivalent to one 10mg capsule of the PQQ supplement, apparently. Some report improved cognitive function & some think otherwise. There's other users that say that they felt energized rather than any "intellectual boost" etc, whilst some seemed to be complaining about the cost rather than investigating WHY nothing seemed to happen.

From what I can tell, many (well, all that I could find) took a lot of different supplements or & foods (such as the natto, as opposed to eating bundles of parsley) & no-one seems to have isolated the PQQ to determine clear results. I think forum members here will be a better judge, since those who have used PQQ have approached it in a vein similar to those controlled tests we often post; where good results are found even when the patient is receiving inflammatory substances. Some foods containing PQQ - Apple, banana, cabbage, carrots, celery, edamamespinach, orange, parsley, green peppers, green tea, kiwi fruit, papaya, potatoes, tomato and tofu. (emphasis mine)

Lastly there's this: _http://examine.com/supplements/Pyrroloquinoline+quinone/

Summary (All Essential Benefits/Effects/Facts & Information)

Pyrroloquinoline quinone (henceforth PQQ) is a small quinone molecule which has the ability to be a REDOX agent, capable of reducing oxidants (an antioxidant effect) and then being recycled by glutathione back into an active form. It appears to be quite stable as it can undergo several thousand cycles before being used up, and it is novel since it associates with protein structures inside the cell (some antioxidants, mostly notably carotenoids like β-carotene and Astaxanthin, are located at specific areas of a cell where they exert proportionally more antioxidant effects due to proximity; PQQ seems to do this near proteins like carotenoids do so at the cell membrane).

The aforementioned REDOX functions can alter protein function and signalling pathways, and while there is a lot of promising in vitro (outside of a living model) research on what it could do there are only a few promising results of PQQ supplementation, mostly related to either altering some signalling pathways or via its benefits to mitochondria (producing more of them and increasing their efficiency).

It is a coenzyme in bacteria (so, to bacteria, this would be something like a B-vitamin) but this role does not appear to extend to humans. Since this does not extend to humans, the designation of PQQ as a vitamin compound has fallen through and it is only considered 'vitamin-like' at best.

PQQ seems to modify oxidation in a cell after binding to some proteins, and this modulatory role it plays can alter the signalling processes that go on in a cell. Due to PQQ being a REDOX agent (capable of both reducing and oxidizing) it is not a pure antioxidant, but it is involved in a cyclical antioxidative cycle with an antioxidant enzyme known as glutathione

For human evidence, the limited evidence we have right now suggests a possible neuroprotective role in the aged (no research in clinical situations of neurodegeneration nor in youth) and it may have an antiinflammatory role. This limited evidence also suggests that the main claim of PQQ, an enhancement of mitochondrial function, occurs in otherwise healthy humans given PQQ supplementation.

The animal evidence that might apply to humans (using oral supplementation at doses similar to what humans use) include a radioprotective effect, possible benefits to insulin resistance, and being a growth factor when PQQ is added to the diet over a long period of time. Higher than normal oral doses in rodents seem to also enhance peripheral neurogenesis (nerve growth outside of the brain) but not necessarily in the brain.

A large amount of the evidence for a direct antioxidant role or the neurological actions related to NMDA signalling of PQQ seem to use very high concentrations in cells, due to possible transportation issues to the brain and low concentrations of PQQ found in the blood following oral ingestion.
It holds a potential to modify signalling in humans, and although the oxidation in the blood (easiest thing to measure) in mostly unaffected it also retains the potential to act as an intracellular antioxidant. The enhancement of mitochondrial function may also occur, but beyond some alterations in signalling and the mitochondrial biogenesis most other properties of PQQ are unlikely to extend to humans
Things to Know
Also Known As

PQQ, Methoxatin


Is a Form of

Pseudovitamin

Stacks Part Of

Anti-Aging

Caution Notice

Examine.com Medical Disclaimer
How to Take (recommended dosage, active amounts, other details)
The optimal dosage of Pyrroloquinoline quinone (PQQ) to be taken daily is currently not known, but extrapolations from animal studies suggest that doses as low as 2mg are somewhat bioactive while most dietary supplements are sold in the 20-40mg range.


Human Effect Matrix
The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Pyrroloquinoline quinone has in your body, and how strong these effects are.
GRADE LEVEL OF EVIDENCE
A Robust research conducted with repeated double blind clinical trials
B Multiple studies where at least two are double-blind and placebo controlled
C Single double blind study or multiple cohort studies
D Uncontrolled or observational studies only
LEVEL OF EVIDENCE
EFFECT CHANGE
MAGNITUDE OF EFFECT SIZE
SCIENTIFIC CONSENSUS COMMENTS
D Stress

Minor
100%
See study
A reduction in self-reported stress has been noted after 8 weeks in persons with self-reported sleep problems; this study also noted improvements in sleep

D Fatigue

Minor
100%
See study
A decrease in fatigue has been noted in older adults with self-reported energy problems

D Sleep Quality

Minor
100%
See study
An improvement in sleep quality has been noted in persons with impaired sleep; it is not certain how PQQ affects persons with normal sleep cycles

D Pain

Minor
100%
See study
In persons with sleep disorders taking PQQ (which improved sleep) there were reductions in pain ratings at the end of the trial

D TMAO

Minor
100%
See study
A decrease in urinary TMAO has been noted with supplementation of PQQ, which is thought to be due to increased activity of the FMO3 enzyme.

D C-Reactive Protein

Notable
100%
See study
The decrease in C-reactive protein seen in one study in otherwise healthy humans reached 45% after three weeks of supplementation.

D Interleukin 6

Minor
100%
See study
IL-6 appeared to be significantly reduced in the serum of adults given PQQ supplementation relative to baseline.

D General Oxidation
100%
See study
Overall oxidation in serum as assessed by TRAP has failed to be significantly influenced by PQQ supplementation in otherwise healthy adults.

D Lipid Peroxidation

Minor
100%
See study
Although a decrease technically exists as assessed by TBARS, the decrease was measured at around 0.2% and is practically irrelevant.

D Liver Enzymes
100%
See study
Serum ALT is not affected by supplementation of PQQ for up to three weeks.

D HDL-C
100%
See study
Three weeks supplementation of PQQ has failed to significantly influence HDL cholesterol levels in otherwise healthy adults.

D LDL-C
100%
See study
No apparent changes to LDL cholesterol exist in otherwise healthy adults given PQQ supplementation daily for up to three weeks.

D Triglycerides
100%
See study
Short term supplementation of PQQ has failed to significantly influence triglycerides in otherwise healthy adults

D Blood Glucose
100%
See study
Short term ingestion of PQQ supplementation in otherwise healthy adults has failed to significantly influence serum glucose concentrations.

Check the link for a better look at the chart.
 
Continued.

Complete Summary Table of Contents:

Sources and Structure
Sources
Structure and Properties
Biological Significance
Molecular Targets
Enzymatic Cofactor
REDOX Signalling
Thioredoxin Reductase 1
Glutathione Reductase
Mitochondrial Biogenesis
PTP1B
Pharmacology
Absorption
Serum
Distribution
Elimination
Mineral Bioaccumulation
Interactions with Neurology
Glutaminergic Neurotransmission
Neuroprotection
Neurogenesis
Neurooxidation
Epilepsy and Convulsions
Hypoxia and Stroke
Brain Injury
Memory and Learning
Sedation
Cardiovascular Health
Cardiac Tissue
Atherosclerosis
Triglycerides
Interactions with Glucose Metabolism
Glucose Deposition
Serum Glucose
Insulin resistance
Interactions with Obesity
Metabolic Rate
Bone and Joint Health
Osteoclasts
Skeletal Muscle and Physical Performance
Mechanisms
Immunology and Inflammation
Mechanisms
Macrophages
Interactions with Oxidation
Singlet Oxygen
Reactive Nitrogen Species
Lipid Peroxidation
Radiation
Peripheral Organ Systems
Liver
Intestines
Kidney
Interactions with Cancer
Leukemia
Melanoma
Interactions with Medical Conditions
Parkinson's Disease
Alzheimer's Disease
Nutrient-Nutrient Interactions
Glutathione
Safety and Toxicology
General
Genotoxicity

Edit1. Sources and Structure

1.1. Sources

Pyrroloquinoline quinone (PQQ) is a quinone molecule that was first identified as an enzymatic cofactor in bacteria, acting as a prosthetic group similar to how B-vitamins work in humans.[1] It is doubtful that PQQ is an enzymatic cofactor in humans, although it still appears to have affinity to proteins in the human body and can bind to them to confer biolgical effects. The proteins that seem to bind to PQQ are called quinoproteins,[2] and via modifying their actions in the body PQQ can exert biological activity.

PQQ was once thought to be a novel vitamin compound, although this view has since had doubts cast upon it and is no longer seen as accurate. Despite the lack of a vitamin role in mammals, it does appear to have growth promoting properties in rodents and may be active in humans following supplementation

PQQ naturally occurs in most foods (in miniscule amounts) although the highest levels can be found in:

Fermented Soybeans products such as Nattō (highest estimate of 61+/-31 ng/g wet weight,[3] lower estimates in the range of 1.42 +/- 0.32ng/g[4])
Green Soybeans (9.26+/-3.82ng/g wet weight)[3]
Spinach (7.02 +/- 2.17ng/g fresh weight)[4]
Rape blossoms (blossoms of the brassica napus plant at 5.44 +/- 0.8ng/g fresh weight)[4]
Field Mustard (5.54 +/-1.50ng/g fresh weight)[4]
Tofu (24.4+/-12.5ng/g wet weight)[3]
Teas from Camellia Sinensis, aka Green Tea (around 30ng/g dry weight of leaves)[3] with the lower range of estimates at 0.16 +/- 0.05[4]
Green peppers, Parsely, and Kiwi fruits (around 30ng/g wet weight or so)[3] although some estimates are lower (2.12 +/- 0.40ng/g for green peppers)[4]
Human Breast milk at 140-180ng/mL (total PQQ and IPQ)[5]
Overall content of PQQ in foods seems to range from 0.19-7.02ng/g fresh weight in one study[4] up to 3.7-61ng/g in another,[6] low numbers may not adequately reflect total content in foods due to excluding IPQ in the measurements whereas higher levels tend to include both PQQ and IPQ.[5]

PQQ is present in a wide variety of foods, but currently the estimates of its contents are quite variable. This may be due to confusion as to whether solely PQQ should be counted or PQQ conjugates (it is not known if these confer dietary benefit). In general, the PQQ content of food products listed above is substantially lower than the content of supplemented PQQ (10-20mg) and food ingestion is unlikely to replicate the effects of supplementation due to the magnitude of difference

It should be noted that due to an affinity of PQQ to bind to amino acids and form imidazolopyrroloquinoline derivatives that the PQQ content of foods may not be the same as the total bioactive amounts of PQQ,[7] probably due to rapid association with proteins forming amino acid conjugates (Imidazolopyrroloquinoline, or IPQ).[8] Human milk, for example, contained 15% PQQ and 85% IPQ derivatives. That being said, no direct studies have been undertaken to see whether PQQ and IPQ have similar or different properties in vivo.

PQQ may form conjugates with dietary protein similar to how it is known to react with proteins in the body, but it is not known if this potential interaction with dietary protein is beneficial or negatively influences bioavailability

1.2. Structure and Properties

Pyrroloquinoline quinone is heat-stable and water soluble,[1] and appears to be stable at ambient temperatures in the form of PQQ disodium salt either as trihydrate (12.7% water[9]) or pentahydrate (22.9% water[10]). It is thought to be a relatively stable REDOX factor in vivo, and is able to carry generally around 20,000 REDOX reactions before degradation,[11][12] and when it carries out REDOX reactions by itself it gets converted into its reduced form known as pyrroloquinoline dihydroquinone (PQQH2)[13] and is replenished (back to the PQQ form) by glutathione.[13]

PQQ binds to proteins via forming a schiff base, which is a spontaneous (no enzyme required) reaction to amino acids found in the protein structures such as lysine.[14] The binding of PQQ to proteins uses the carbonyl groups (C=O),[15] including the three carboxylic groups opposite of the two ketones used in REDOX reactions.



Pyrroloquinline quinone (PQQ) is a quinone structure with three carboxylic acid groups which are used to bind to proteins, and two ketone groups which are involved in the REDOX capacities of the molecule

In some in vitro studies, combining PQQ with reducing agents (SIN-1, sodium borohydride) can form a green precipitate[16] and the reddish coloration of PQQ turns increasing brown when water content is removed.[9]

PQQ (as a powder) appears to be able to change color depending on its hydration status and oxidation status

1.3. Biological Significance

PQQ was initially thought to be synthesized via the α-amino adipic acid-Δ-semialdehyde (AASDH; also known as U26) enzyme[17] although this seems to be incorrect[18][19] since despite this protein having many PQQ binding sites[20] its mRNA levels are not negatively regulated by PQQ levels[21] which would most likely occur if the enzyme synthesized PQQ. It is known to be synthesized (in bacteria) from the amino acids L-Tyrosine and glutamate[22][23] in a process requiring a series of enzymes labelled PqqA-F where PqqA formed the peptide precursor and the other enzymes structurally modify it into active PQQ.[24]

Although mammalian synthesis is not certain, PQQ does occur normally in the mammalian body[25] and approxiamtely 100-400 nanograms of PQQ are thought to be made in humans each day;[3][26] leading some authors to claim an estimated tissue concentration of approximately 0.8−5.9ng/g in humans.[6]

Since complete deprivation from the diet of animals has been shown to hinder growth and reproductive performance,[27][28] it was initially thought that this (paired with the initial guess of endogenous synthesis via AASDH) indicated a vitamin deficiency. However, due to the definition of vitamins being one that requires a disease state to occur during deficiency[17] and no apparent dysfunction aside from impaired growth seen with PQQ deficeincy it was not classified as an essential vitamin;[18] this claim of no vitamin-like property being supported by the idea that AASDH is not actually used for PQQ sythesis in humans.[18][19]

Pyrroloquinoline quinone (PQQ) is known to occur in both the diet and in mammalian tissue, and appears to have biological activity in the body. It was initially thought to be a new vitamin, but this conclusion seems unlikely and it is more likely a bioactive non-vitamin compound.

PQQ has been investigated for being a growth factor in youth (since deprivation in rats impairs growth[27][28]), secondary to its effects at improving mitochondrial biogenesis (making more mitochondria) at seemingly effective doses of 0.2-0.3mg/kg foodstuff (in mice),[29] which is surprisingly close to the levels found in human breast milk.[5] Preliminary evidence for mitochondrial efficacy has also been noted in adult humans given 0.075-0.3mg/kg daily,[30] with the latter dose being close to the recommended 20mg serving for a 150lb adult.

PQQ is thought to be a non-vitamin growth factor, in part due to its naturally high levels in breast milk and reduced growth in rats without dietary PQQ. It may do so via beneficially influencing mitochondrial function

It is seen as a novel REDOX catalyzing agent due to its stability, which prevents most self-oxidation (seen in catechins) and polymerization (tannins).[11] A case has been made that PQQs effects are constant between species and bacteria, which aims to validate extrapolation from one species to humans.[11] The potency of PQQ and its quinoproteins in REDOX cycling appears to be approximately 100-fold greater than Vitamin C or other polyphenolic compounds, when in alkaline conditions.[26][31][32]

PQQ, after associating with proteins (not in the role of a cofactor) appears to be capable of REDOX cycling suggesting that it can have conditional prooxidant and antioxidant roles. The association with proteins suggests that it can modify their structures either directly or via modifying the levels of oxidation at the level of the protein (similar to how carotenoids such as Astaxanthin are located at the cellular membrane which localizes their effects)

Edit2. Molecular Targets

2.1. Enzymatic Cofactor

Pyrroloquinoline quinone (PQQ) was discovered in 1979 as an enymatic cofactor in bacteria;[33] preliminary evidence in pig kidneys and adrenal glands suggested a similar role in mammals.[34][35][36][37] Doubts were later cast upon the role of PQQ as a mammalian enzymatic cofactor,[38][39][40] and currently the consensus is that PQQ is unlikely to be an enzymatic cofactor in humans as it is in bacteria and plants.

Pyrroloquinoline quinone (PQQ) was first discovered as a bacterial enzymatic cofactor (being required by bacterial enzymes to function properly) and preliminary evidence suggested it could play the same role in mammals, which would make PQQ a vitamin. But further study found no quality evidence supporting this role in mammals; it is currently believed that PQQ does not act as an enzymatic cofactor in humans

2.2. REDOX Signalling

REDOX (REDuction OXidation) signalling refers to stimulation or inhibition of cellular signalling systems by molecules that can switch from an oxidized state to a reduced state, such as the well-known REDOX-acting supplements Vitamin C and Alpha-Lipoic Acid.[41] Pyrroloquinoline quinone (PQQ) may have this property as well, although its primary mode of action seems to be acting on known REDOX proteins in the cell; this is in line with its high binding affinity for some proteins, despite not acting as their coenzyme.[42][22] For example, PQQ may function as a mammalian growth factor via signal transduction modification by both oxidation and redox cycling[43], and has been shown to improve insulin signalling in mice by redox cycling.[44]

PQQ may have an indirect influence on REDOX signalling in a cell by modifying the actions of proteins, which may underlie some antioxidative (and prooxidative) changes in a cell similar to any other REDOX agent

2.3. Thioredoxin Reductase 1

PQQ has been noted to partially inhibit thioredoxin reductase 1 (TrxR1), which is an enzyme in the cytosol that reduces thioredoxin.[45] PQQ has low potency yet high affinity in binding to TrxR1 and seems to outcompete thioredoxin binding.[46] When PQQ binds to TrxR1, the enzyme's activity is modified so it acts more on an alternate substrate known as juglone.[47] Overall, NADPH oxidase activity of TrxR1 (a measure of the activity of this enzyme) is increased in the presence of 10-50µM PQQ due to increased activity of the TrxR1-Juglone interaction.[47]

Pyrroloquinoline quinone (PQQ) binds to an antioxidant enzyme (TrxR1) and alters its function, reducing its affinity towards its normal substrate and increasing its affinity towards an alternate substrate. Overall activity of this enzyme appears to be enhanced at high concentrations of PQQ, but the effect of more physiologically realistic (nanomolar) concentrations are not known

Inhibition of TrxR1 activity is known to cause an increase in the activity of the Nrf2 protein, which acts on the nucleus (via the antioxidant response element or ARE) to increase antioxidant gene expression.[48][49][50] Since oral supplementation of PQQ appears to influence a large amount of genes under control of TrxR1-related transcripts[51] it is thought that TrxR1 inhibition by PQQ occurs in vivo.[51]

It is thought that PQQ inhibits thioredoxin reductase (TrxR1) when ingested orally, since genes that would normally be activated when TrxR1 is inhibited do seem to be activated with PQQ in rats

2.4. Glutathione Reductase

PQQ has also been shown to inhibit glutathione reductase, but despite a decreased KM towards juglone (which would increase NAPDH oxidation and enzyme activity) the Kcat was also reduced and enzyme activity remains similar with or without PQQ.[47] However, GSSG reduction with 5µM PQQ was reduced approximately 2-fold relative to control.[47]

An inhibitory effect has been noted in regards to glutathione reductase as well, although the practical significance of this particular enzyme interaction is not known

2.5. Mitochondrial Biogenesis

In rats, PQQ depletion is known to influence genetic expression (238 out of 10,000 tested genes) and dietary repletion is known to influence 847 transcripts;[51] of these, the major pathways affected include Thioredoxin and MAPK signalling but also PGC-1α, a positive regulator of mitochondrial biogenesis[52]).[51] PQQ activates PGC-1α via CREB phosphorylation[53] and appears to positively regulate mitochondrial biogenesis in vivo. It also has other possible roles in blood pressure regulation, cellular cholesterol homeostasis, energy production, and protection of mitochondrial activity, all of which are beneficially associated with increased PGC-1α activity[11][52]).

When studies are undertaken in rats comparing a PQQ deficient diet, in which the rats must rely solely on de novo biogenesis of PQQ) against PQQ sufficient diets, the PQQ supplemented diets tend to promote up to 20-30% more mitochondria in the liver (on a mass basis, as assessed by mtDNA) over the rats' lifetime.[29][27][11][54][8][51][53] Decreased permeability of the mitochondrial membrane has also been noted without alterations in functional capacity or mitochondrial size,[27] along with the mitochondrial count per cell increasing 60% from 56.8+/-7.8 to 91+/-6.6 with 2mg/kg PQQ fed by gavage starting from 2 weeks of age in rats on a PQQ deficient diet.[27]

Pyrroloquinoline quinone (PQQ) appears to be capable to increasing the activity of PGC-1α, which then promotes mitochondrial proliferation and membrane stabilization. This occurs in rats using oral doses similar to those in humans, and occurs secondary to CREB phosphoylation; this may suggest bioenergetic benefits of supplementation, but human evidence does not yet exist

When humans supplement PQQ (0.075-0.3mg/kg for one week at a time for each dose), urinary lactate decreased by 15% along with a reduction in urinary pyruvic acid.[30] A minor reduction of fumarate was noted, but other Kreb's cycle intermediates (Isoaconitate, Citric acid, 2-oxoglutarate, and succinate) were not altered in the urine.[30] It was hypothesized, on the assumption that urinary metabolites reflect cellular energy status, that this indicated an increase in mitochondrial efficiency.[55][56]

A nonsignificant decreasing trend in urinary 4-hydroxyphenylacetate was noted with PQQ;[30] decreases in this and other urinary metabolites tend to suggest increased β-oxidation rates.[57]

The currently lone human study using doses of PQQ commonly found in supplements suggest that supplementation may increase mitochondrial efficiency

2.6. PTP1B

Pyrroloquinoline quinone (PQQ) is known to enhance signalling of some MAPK proteins, most notably ERK1/2, to significant extents, rivalling its effects on thioredoxin and PGC-1α.[51][58] This may be secondary to oxidative changes on the PTP1B protein; the changes occur when PQQ facilitates the production of hydrogen peroxide by associating with other proteins[59]) within a cell via direct REDOX cycling.[43] Hydrogen peroxide then modifies PTP1B on Cys-215.[60] The change of Cys-215 from a sulfenic acid moiety (-SOH) into a more oxidized sulfinic acid (–SO2H) or sulfonic acid (–SO3H) causes reversible inhibition of PTP1B.[61][62]

PTP1B is a negative regulator of the insulin receptor,[63] and is also a negative regulator of the epidermal growth factor receptor (EGFR).[60] By alleviating a negative inhibition, PQQ (via H2O2) can enhance signalling through the EGFR resulting in more ERK1/2 activation.

By acting as a direct REDOX couple, PQQ can inhibit PTP1B activity via hydrogen peroxide production within a cell. This inhibition of PTP1B enhances growth factor signalling (via EGFR signalling) and can enhance insulin sensitivity in a cell (by enhancing insulin receptor signalling)

Edit3. Pharmacology

3.1. Absorption

PQQ is absorbed well in the intestines, but its absorption is highly variable; 62% of PQQ is absorbed on average in rats in a fed state, with a range from 19-89%.[64]


3.2. Serum

A single dose (0.2mg/kg) of PQQ ingested by humans in a fruit-flavored drink has a tmax of about two hours and a Cmax of approximately 9nM.[30] Doubling PQQ dose from 0.075mg/kg PQQ daily for one week to 0.15mg/kg and then 0.3mg/kg in healthy subjects increased plasma PQQ levels in a linear manner. Fasting blood levels of PQQ ranged from 2 to 14nM when measurements were taken on day four of supplementation.[30] These levels may be similar to the steady state values as they were measured after the fourth day of dosing on the morning after PQQ was ingested.[30]

Daily supplementation of pyrroloquinoline quinone (PQQ) appears to increase plasma PQQ concentrations to a steady state level of around 10nM in humans

3.3. Distribution

PQQ appears to be eliminated from mice 24 hours after ingestion except in the skin and kidneys, which retain detectable levels of PQQ following oral ingestion.[64] In the skin, it was noted that 0.3% of the ingested dose was detectable six hours following a dose and 1.3% of the oral dose was detected after 24 hours. Greater than 95% of the PQQ in the blood seems to be associated with the blood cell fraction, with less than 5% remaining in the plasma fraction.[64]


3.4. Elimination

86% of an ingested dose of PQQ in mice appears to be eliminated via the kidneys within 24 hours of oral ingestion[64] and is excreted in a manner directly correlated with serum levels in humans;[30] in humans, less than 0.1% of the ingested dose is detected as unmodified PQQ, suggesting that PQQ is highly metabolized prior to elimination.[30]


3.5. Mineral Bioaccumulation

Pyrroloquinoline quinone has been noted to bind directly to metals such as uranium. This explains the toxicity of uranium to bacteria, which depend on PQQ as a cofactor for enzymes;[65] uranium displaces a calcium ion which is required to bind PQQ to certain enzymes in bacteria.[66][67]

Pyrroloquinoline quinone has a known affinity for some minerals, but the role of PQQ in the human body in regards to minerals is not known. It is unlikely to play a role in heavy mineral elimination due to the very low serum concentrations of PQQ

Edit4. Interactions with Neurology

4.1. Glutaminergic Neurotransmission

The NMDA receptor possesses a sulfhydryl REDOX modulatory site that is susceptible to oxidation[68] where oxidation suppresses NMDA signalling and reduction enhances NMDA signalling.[69][70] PQQ (50µM) does not affect basal currents through the receptor, but it can block reducing agents from enhancing signalling[71][72] in the 5-200µM range. The reduction of signalling is thought to be due to acting on the REDOX site, since PQQ can reduce excitotoxicity but fails to protect from H2O2 (which causes toxicity independent of the NMDA receptor).[73]

This mechanism is thought to underlie protective benefits of PQQ supplementation[72] seen at low concentrations of 5µM (other mechanisms require PQQ concentrations of up to 50µM in order to become appreciable).[73]

PQQ appears to have a regulatory effect on the glutamate receptor known as NMDA, by causing some oxidation of the REDOX site and preventing excess reduction from occurring it can suppress abnormal spikes in NMDA signalling; since an excess of NMDA signalling can be toxic, the result is a neuroprotective effect. This is thought to be applicable to oral supplementation due to a low concentration being required

4.2. Neuroprotection

100µM PQQ has been noted to protect cells from glutamate-induced cytotoxicity[74][75] associated with an increase in antioxidant enzyme activity, as assessed by Nrf2 and HO-1.[74] This is thought to be downstream of Akt/PI3K and GSK-3β activation,[76] of which the former is known to occur with PQQ in the 50-100µM range in vitro.[76]

PQQ also appears to prevent an increase in JNK signalling seen with NMDA-mediated toxicity, but it is not related to the protective effects on cellular survival[76] and PI3K activation cannot fully predict the protective effects of PQQ.[74]

PQQ appears to be related to an activation of PI3K/Akt signalling, which is known to cause an induction in antioxidant enzymes via Nrf2. This is thought to underlie some of the protective benefits of PQQ on cellular structure seen in vitro, but its significance to oral supplementation is not known

Protective effects against glutamate have been noted when PQQ is directly injected into the brain in a manner that is associated with the aforementioned antioxidant effects (PI3K activation and Nrf2/HO-1 induction).[75]

Injections of PQQ into the brain are known to be neuroprotective, but it is not known if this applies to oral ingestion as well

4.3. Neurogenesis

In fibroblastic cells (L-M), incubation of PQQ disodium salt (approximately 100µg/mL) for 24 hours has resulted in a peak 40-fold increase in Nerve Growth Factor (NGF) synthesis, with minor (around 5 to 10-fold) increases at 10-20µg/mL[77][78] in a manner dependent on COX2 induction[79] and PI3K/Akt.[80] Prostaglandins D2 and E2 (from Arachidonic acid) have been reported in vitro,[79] and while they were not tested as a mandatory intermediate the former (and its metabolite prostaglandin J2) are known to promote NGF synthesis in the 6.3-25µg/mL range[79] via CHRT2[81] extending to a variety of cell lines.[82][83][84]

This increase in NGF synthesis has also been noted in isolated mouse astrocytes exceeding Alpha-Lipoic Acid (ALA) in potency, but less than ALA in c/3T3 (embyotic fibroblast) cells.[85]

When tested in vitro, PQQ appears to concentration-dependently increase NGF synthesis up to a peak efficacy at 100µg/mL. The increase noted in isolated cells appears to be quite large. Eicosanoid signalling appears to be involved in this phenomena, suggesting that PQQ works via manipulating the actions of eicosanoids

When fat-soluble derivatives were tested (PQQ trimethyl esters) at injections of 0.1-1mg/kg every other day, it was noted that peripheral sciatic nerves had enhanced regeneration;[77] injections into the periphery failed to cause an increase in NGF in the neocortex, thought to be due to poor diffusion of PQQ across the blood brain barrier due to complexation with proteins in serum.[77] A pharmaceutical modification of the PQQ enzyme (oxapyrroloquinoline; OPQ) was able to enhance brain NGF concentrations,[77] and since OPQ is known to be metabolized into PQQ in bacteria (hypothesized to occur in rodents) and is fat soluble it was thought to act as a prodrug.

When tested later, PQQ added to silicon tubes confirmed an increase in the rate of physical recovery in a mouse model of physical nerve injury with benefits seen after four weeks extending to twelve weeks.[86] This improvement was associated with an increase in well-myelinated neurons.[86]

In a spinal cord injury model, 5mg/kg PQQ injected into the spine daily for a week after injury was able to suppress the expression of iNOS after one day (a biomarker for inflammation[87][88]) and improved both locomotor performance and neuronal health (axonal density) in the area relative to control.[89] Benefits to peripheral nerve function (in a rat model of sciatic nerve injury) have been noted orally; a low dose (20mg/kg) prevented hyperalgesia from the nerve injury while only the higher dose (40mg/kg) prevented muscular atrophy and lipid peroxidation.[90]

The enhancement of neurogenesis has been noted in the periphery (tissue excluding the brain) with injections of low doses of PQQ, but an increase in neurogenesis in the brain has failed to be noted which is thought to be due to transportation issues to the brain. While there are no oral studies in rodents yet, PQQ has been noted to enhance peripheral neurogenesis following nerve injuries

4.4. Neurooxidation

As mentioned in the glutaminergic section, the oxidative effects of PQQ on the NMDA modulatory site[71][72] can ultimately cause a reduction in NMDA-induced superoxide formation in the neuron[73] at concentrations (5uM) that do not affect oxidation per se (no effect against hydrogen peroxide which circumvents the receptor).[73]

The anti-glutaminergic effects that occur at lower concentrations may also ultimately cause anti-oxidative effects by suppressing NMDA signalling, despite this mechanism being reliant on the pro-oxidant effects of PQQ

PQQ does not appear to influence the toxicity of peroxynitrate (a combination of nitric oxide and the superoxide radical), despite inhibiting its formation.[91] When using SIN-1 as a way to produce peroxynitrate and induce cell death in vitro, PQQ at 100uM abolished cell death prior to peroxynitrate formation with an EC50 of 15+/-8.4uM, yet actually potentiated pre-existing peroxynitrate toxicity (also seen with superoxide dismutase, an anti-oxidant enzyme, when catalase was not present).[16] The mechanism appears to be through sequestering the superoxide radical without significantly influencing nitric oxide, as PQQ does not appear to modify many parameters of nitric oxide or peroxynitrate per se yet potentiated a SIN-1 induction of cGMP and production of nitrate, theoretically caused by a backlog of nitric oxide that could not convert to peroxynitrate due to less free superoxide radicals.[16] Interactions with PQQ and superoxide radicals has been noted previously.[92][93]

Can prevent superoxide radical induced cell death, but does not significantly influence nitric oxide cell death per se

4.5. Epilepsy and Convulsions

NMDA receptors are involved in the pathology of seizures (as seizures are involved with excessive NMDA signalling[94][95]) and the REDOX modulatory site that PQQ is known to interact with (suppressing high levels of activity) is further implicated[96] since seizures are associated with a high level of reducing agents in the brain[97][98] which can act upon that site to promote increased NDMA signalling;[96] it is thought that PQQ could have a therapeutic role (seen with pharmaceutical NMDA antagonist[99][100]) since by its oxidative role it hinders this particular site on NMDA receptors[71][72] and PQQ is thought to not associated with side-effects from excess suppression due to only suppressing high levels of NMDA signalling but not basal levels.

When seizures occur, they are potentiated by excessive signalling through the NMDA receptors and due to this NMDA receptor antagonists (or anything that can suppress excess signalling) are thought to be therapeutic. Since PQQ has been implicated in suppressing excess NMDA signalling, it is being investigated for anti-epileptic effects

Application of 200µM PQQ to isolated neurons undergoing epileptic activity can fully abolish such activity if induced by reducing agents (no effect on epileptic activity induced by other means),[96] supporting the role PQQ plays in epilepsy via NMDA antagonism which may occurs to limited levels at concentrations as low as 5µM.[73]

In vitro evidence support a role for PQQ, but due to quite high concentrations being used (relative to what is seen in the blood) and a hypothesized low transportation to the brain it is not sure if this will occur in a living organism following oral ingestion

4.6. Hypoxia and Stroke

Pyrroloquinoline quinone (PQQ) appears to have protective effects against ischemia (assessed by infart size) when 10mg/kg is injected either 30 minutes prior to ischemia (reducing the infarct size from a 95+/-3.6% increase to 68.8+/-10.4%)[101] and is slightly less effective when injected immediately after rather than preloaded (37.6% reduction seen previously reduced to 18.5%).[101] This has been replicated elsewhere with 3-10mg/kg (70-81% protection) but not 1mg/kg was given an hour after MCAO injury.[102]

Injections of PQQ have been noted to have protective effects in rats subject to stroke, but due to high injection doses being used and the low dose being ineffective preliminary evidence does not appear to look promising for oral supplementation of PQQ in this role; oral testing, however, has not yet been conducted

4.7. Brain Injury

Injections (intraperitoneal) of PQQ in the range of 5-10mg/kg to rats for three days prior to tramautic brain injury was able to dose-dependently protect the brain from injury with the highest dose appearing to confer absolute protection (assessed by histology and cognitive behaviour post-injury).[103]


4.8. Memory and Learning

When injected into rats at 10mg/kg bodyweight, PQQ does not appear to cause overt behavioural changes in regards to sedation, activty, or heart rate[101] with no alterations in EEG readings being observed.[101]

Several morphological changes are associated with PQQ that may confer pro-cognitive effects, such as proliferation of Schwann cells secondary to PI3K/Akt activation,[80] PQQ is also able to induce production of Nerve Growth Factor (NGF)[78] secondary to COX induction;[79] increases in NGF have been observed in vivo when using trimethylesters (for permeability into the brain) with a maximal increase of 1.7-fold over baseline associated with a PQQ metabolite named oxazopyrroloquinoline.[77]

PQQ supplementation has also been associated with preventing stress-associated (oxidative stress mediated) declines in memory[104] reducing damage done by methylmercury toxicity,[105][106] and reducing memory impairment induced by a lack of oxygen;[107] at 20mg/kg bodyweight PQQ has a potency nonsignificantly different than 200mg/kg Vitamin E (as R-R-R-Alpha tocopherol) in reversing age-related memory decline in rats.[107] which, together with its neuroprotective status, assure it a position as a rehabilitative Nootropic.

Currently, one study has been conducted in humans using PQQ at 20mg daily or using PQQ at 20mg paired with 300mg CoQ10.[108] This study used the supplements once-daily at breakfast for 12 weeks in persons aged 51.7-52.3yrs with the three tests being a Verbal Memory test (seven words read aloud and then asked to recite), the Stroop Test, and the CogHealth test. The results suggested a tendency towards improvement in the Verbal memory test (nonsignificant) a significant increase in performance in the Stroop test with PQQ+CoQ10 but not PQQ in isolation, and the choice reaction and simple reactions subsets of the CogHealth test showed statistically significant improvements with PQQ and PQQ+CoQ10 but the degree of improvement was not recorded.[108]

General nootropic benefit for those with impaired cognitive function (due to age, neural damage, etc.) but does not have ample evidence to be claimed a cognition promoting nootropic in otherwise healthy. The one study conducted in humans does not claim a 50% or doubling of memory, and was not suited to answer this question

4.9. Sedation

One open-label human study conducted with 20mg 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 4 weeks after usage while a decrease in sleep latency required 8 weeks to reach significance.[109] This study also noted improved appetite, obsession, and pain ratings that may have been secondary to improved sleep; contentness with life trended toward significance over 8 weeks but did not reach.[109]


Edit5. Cardiovascular Health

5.1. Cardiac Tissue

Protective effects have been noted in cardiac myocytes subject to ischemia, secondary to scavenging of peroxynitrate radicals, at injectible doses of 15mg/kg bodyweight 30 minutes prior to ischemia.[110][111] PQQ was studied alongside metprolol as a combiantion anti-oxidant/beta-blocker therapy, and 3mg/kg PQQ and 1mg/kg metprolol were both insignificantly different in reducing mortality (40% of control passed, 8% of PQQ and 14% of metprolol) while no deaths were recorded in combination therapy.[112] Combination was also more effective in reducing infarct size relative to either therapy in isolation, and both groups using PQQ had a reduction of creatine kinase release that was insignificantly different between groups.[112]

The combination therapy study noted increased cardiac mitochondrial respiration with PQQ but neither metprolol nor PQQ+metprolol, and respiration was further increased even in the contrl groups with no ischemia/reperfusion done.[112]

Secondary to the pro-mitochondrial effects and anti-oxidative effects during ischemia/reperfusion, PQQ appears to be cardioprotective under certain contexts

5.2. Atherosclerosis

In otherwise healthy humans supplementing PQQ at 0.075-0.3mg/kg for three weeks (increasing the dose each week), supplementation was associated with a decrease in C-reactive protein concentrations in serum (45%).[30] This study also noted that urinary trimethylamine-N-oxide (TMAO) was reduced[30] and since both C-reactive protein (CRP)[113] and TMAO[114] are thought to be biomarkers for atherosclerosis PQQ is thought to have a role.


5.3. Triglycerides

In rats fed a PQQ deficient diet relative to the same diet fed with 2mg/kg PQQ, plasma diglycerides and triglycerides (DAG and TAG) were elevated 20-50% (higher value related to triglycerides) in the PQQ deficient diet relative to 2mg/kg with no significant difference in free fatty acids,[29] which is similar to levels previously seen with this experimental protocol.[27] The elevation of triglycerides in the deficient mice does not influence the n3/n6 omega fatty acid ratios.[29]

The increase seen in triglycerides may be due to this study being conducted for a long period of time, where previous research has demonstrated that PQQ deficient diets reduce mitochondrial density by 20-30%[27] and levels of mRNA for PPAR, Fatty Acid binding protein, and Acyl CoA oxidase being significantly reduced with PQQ deficiency.[29] Additionally, higher levels of beta-hydroxybutryic acid (indicative of less beta-oxidation) were seen in PQQ deficient rats. Inducing PQQ deficiency from a sufficient state can also elevate triglyceride levels to almost two-fold the previous levels, with the trend being reversed upon acute administration of PQQ in pharmacological amounts (2mg/kg bodyweight).[51]

Appears to reduce triglycerides very potently (to a greater extent than Fish Oil, empirically) in research animals relative to a PQQ deficient diet, and this is thought to be due to increased mitochondrial β-oxidation of fatty acids

The one human study to use supplemental PQQ (0.075-0.3mg/kg for three weeks in escalating doses) failed to find any significant influence on triglyceride concentrations in serum of otherwise healthy adults consuming a standard (but uncontrolled) diet.[30] This study also noted alterations in urinary metabolites (4-Hydroxyphenylacetate and 4-Hydroxyphenylactate) suggestive of an increase in mitochondrial β-oxidation despite no apparent changes in triglycerides.[30]

First study to assess the effects of PQQ on triglycerides has failed to find an influence in otherwise healthy humans

Edit6. Interactions with Glucose Metabolism

6.1. Glucose Deposition

PQQ (500nM) has been noted to inhibit protein tyrosine phosphatase 1B (PTP1B) secondary to producing H2O2[43] (H2O2 is known to inactivate PTP1B in a reversible manner[60]), and aside from PTP1B being a negative regulator of a growth factor receptor (EGFR[60]) it also negatively influences insulin receptor signalling;[63] inhibition of PTP1B, seen also with Berberine and Ursolic Acid (albeit by different mechanisms), tends to increase the activity of the insulin receptor.

Sequestering the hydrogen peroxide made from PQQ appears to block its inhibition on PTP1B.[43]

Via prooxidative changes within a cell, PQQ can produce hydrogen peroxide which then impairs PTP1B function. Since PTP1B normally suppresses signalling via the insulin receptor, the result is a compensatory increase in insulin signalling

6.2. Serum Glucose

In young rats (before sexual maturation), PQQ either at 3mg/kg in the diet or having a PQQ deficient diet does not seem to significantly affect blood glucose or insulin levels.[29] An increased glucose AUC was seen when PQQ deficient mice were subject to an oral glucose tolerance test, but no single time point was significnatly different.[29] Injections of PQQ at 4.5mg/kg bodyweight also did not significantly influence blood sugar or insulin levels in healthy rats, but was able to significantly reduce glucose AUC (by 7%) and glucose disposition in diabetic rats fed glucose and injected with PQQ, with no effect of PQQ on fasting glucose levels in rats.[29]


6.3. Insulin resistance

It has potential for alleviating fat-induced insulin resistance (characterized by a dysregulation in beta-oxidation of the TCA cycle) by increasing mitochondrial biogenesis in muscle cells, similar to exercise.[115]

At this moment in time, nothing remarkable about PQQ and glucose metabolism

Edit7. Interactions with Obesity

7.1. Metabolic Rate

When comparing a rat diet deemed sufficient in dietary pyrroloquinoline quinone (PQQ; 2mg/kg) to a diet deficient in one, the deficient diet appeared to have a decreased metabolic rate (reaching only 90% of the control rats)[29] with the difference being more prominent during the fed rather than fasted state;[29] it appears that this decreased metabolic rate did not influence the rats of lipolysis nor glycolysis as assessed by the respiratory quotient.[29]

Depleting the rat diet of PQQ appears to reduce their metabolic rates relative to a diet with adequate levels of PQQ, but no studies have investigated whether an increase in metabolic rate occurs with extra supplemental PQQ

Edit8. Bone and Joint Health

8.1. Osteoclasts

Pyrroloquinoline quinone (PQQ) has been noted to inhibit RANKL-induced osteclast formation in RAW 264.7 macrophage-like cells at a concentration of 10µM, which occurred at all stages of cell maturation.[116]

RANKL normally signals through the transcription factor NFATc1[117][118] via a particular AP-1 signalling protein that contains c-Fos and c-Jun.[119][120] PQQ inhibited c-Fos induction from RANKL,[116] but other RANKL-induced proteins (nF-kB and MAPKs) were unaffected suggesting that RANKL signalling overall was unaffected.[116]

There is a negative regulatory pathway from RANKL, where RANKL increases IFN-β production which signals via its receptor (IFNAR[121]) to activate STAT1 and JAK1 to suppress the actions of RANKL.[122][123] IFN-β was not affected by PQQ, but the receptor expression (and its targets) appeared to be increased which were thought to underlie the observed inhibitory effects seen with PQQ.[116]

PQQ appears to enhance the negative feedback mechanism controlling osteoclastogenesis (production of osteoclasts, which are negative regulators of bone mass) and via this enhancement overall osteoclast activity is hindered somewhat and this is thought to promote bone mass over time. Due to a higher than normal concentration being used, it is not sure if this occurs following oral supplementation

Edit9. Skeletal Muscle and Physical Performance

9.1. Mechanisms

One study using 0.075-0.3mg/kg PQQ supplementation daily for three weeks (increasing with dose each week) in otherwise healthy adults has noted a decrease in overall urinary amino acid levels by approximately 15%,[30] with the decrease in some (serine, asparangine, aspartic acid) being biomarkers for skeletal muscle consumption of nitrogen (via being converted into Glutamine and alanine[30][124]).

Preliminary evidence suggests that oral PQQ supplementation can influence skeletal muscle metabolism in otherwise healthy humans with standard supplemental doses, but the practical significance of this is not yet known

Edit10. Immunology and Inflammation

10.1. Mechanisms

PQQ appears to have some interactions with the immune system, as deprivation of PPQ from the diet (relative to a PQQ sufficient diet) appears to cause abnormal immune function in mice, with altered immune response after stressors.[54][8]

A study on parental (intravenous) nutrition found that the addition of 3mcg PQQ to the parental nutrition in mice was able to increase the count of CD8+ cells and lymphocytes in intestinal Peyer's Patches, although not to the level of oral control.[125]


10.2. Macrophages

Application of PQQ to macrophages in vitro was able to prevent osteoclast differentiation at doses as low as 0.1uM (but more potency at 10uM) secondary to increasing IFN-β secretion; IFNβ is a negative regulator of osteoclast differentiation normally released after inflammation, and PQQ increases its release (and subsequent suppression), which is also demonstrated by increased levels of proteins induced by IFN-β (iNOS, STAT1, JAK1).[116] PQQ was found to phosphorylate nF-kB, p38, and IKKβ in these cells which is a pro-inflammatory response in macrophages.[116]

Practical relevance unknown

Edit11. Interactions with Oxidation

11.1. Singlet Oxygen

The reduced form of pyrroloquinoline quinone (PQQ), known as pyrroloquinoline equinol or dihydroquinone pyrroloquinoline (PQQH2) appears to be able to sequester singlet oxygen (1O2) with a potency 6.4-fold less than β-carotene as reference yet higher than that of Vitamin E (2.2-fold) and Vitamin C (6.3-fold).[13]

PQQH2 appears to be produced (via reduction) from PQQ when in a buffer in the presence of glutathione[13] and this process is known to use the semiquinone (PQQH) as an intermediate;[59] exposure to oxygen either by ambient atmosphere or by singlet oxygen readily oxidizes PQQH2 back into PQQ.[13] This suggests that glutathione is capable of recycling PQQ as an antioxidant.

PQQ and its reduced form PQQH2 appear to form a cyclical relationship where PQQH2 sequesters oxygen radicals, and glutathione reduces it back into PQQ so it may sequester more radicals; the potency of this reaction, on a molecular level, seems intermediate to β-carotene (PQQ is lesser) and Vitamin C/E (greater)

11.2. Reactive Nitrogen Species

One study assessing whether PQQ could directly sequester peroxynitrate (ONOO-) failed to find such a property of PQQ, as despite protecting cells form the toxic effects of SIN-1 (produces nitric oxide and superoxide radicals,[126] of which PQQ scavenged the superoxide radicals[16]) the toxicity of peroxynitrate directly was not protected against (in fact, it appeared to be augmented at 100-300µM PQQ).[16]

Pyrroloquinoline quinone (PQQ), even at impractically high concentrations, does not appear to direct sequester reactive nitrogen species (nitrogen based pro-oxidants) such as peroxynitrate

11.3. Lipid Peroxidation

One human study using supplemental pyrroloquinoline quinone (PQQ) and measuring serum antioxidant capacity via TBARS and TRAP values failed to find any significant influence on TRAP values but noted a decrease in TBARS (indicative of lipid peroxidation) to the degree of 0.2% when measured at peak serum PQQ values (6-12nM) seen with up to 300µg/kg supplementation;[30] this decrease in TBARS was noted to be significantly less than other dietary supplements such as procyanidins from Cocoa Extract which (560mg) can reduce TBARS by 25-35%[127] or sources of anthocyanins such as Aronia melanocarpa or Blueberry.

The decrease in serum biomarkers of lipid peroxidation that is known with PQQ supplementation is probably much too low to be indicative of anything significant

11.4. Radiation

Oral ingestion of 4mg/kg PQQ to mice (more effective than both 2mg/kg and 8mg/kg, as well as the reference drug of 10mg/kg nilestriol[128]) appears to reduce death from gamma irradiation when given an hour before and again seven days after irradiation; damage to select cells tested (white blood cells, reticulocytes, bone marrow cells) was also reduced with 4mg/kg PQQ supplementation to mice.[128]

Oral ingestion of PQQ (estimated human equivalent of 0.32mg/kg) appears to be able to protect mice from gamma irradiation to a respectable degree

Edit12. Peripheral Organ Systems

12.1. Liver

An intraperitoneal injection of pyrroloquinoline quinone (PQQ) to rats at 5mg/kg twice before CCl4 liver toxicity appeared to exert protective effects;[129] when tested in vitro, PQQ showed protective effects in isolated liver cells with most potency at 3µM.[129]


12.2. Intestines

Due to the involvement of pyrroloquinoline quinone (PQQ) in bacteria (from where it was discovered in 1979[33]) and the involvement of quinoproteins in the fermentation process [130] (which PQQ associates with) and the above higher count of PQQ recorded in fermented foods; it is hypothesized that fermentation may increase PQQ content. Interestingly, common strains of bacteria in the human intestinal tract do not appear to synthesis much PQQ[131][132] and in antibiotic fed mice (lacking intestinal microflora) it seems that dietary intake is the major determinent of bodily PQQ levels.[132]

Pyrroloquinoline quinone was thought to be synthesized by intestinal bacteria due to its discovery being that of a bacterial cofactor, but preliminary evidence does not support the intestinal microflora as a major producer of PQQ in the body

12.3. Kidney

Pyrroloquinoline quinone (PQQ) was once implicated in being an enzymatic cofacter for diamine oxidase (pig kidney)[34][35] and DOPA decarboxylase (pig kidney)[36] (as well as dopamine β-hydroxylase, albeit in the renal medulla[37]), although it is generally accepted to not be a significant component of eukaryotic enzymes in vivo (in the role of a cofactor) like it is in bacterial and plant enzymes.[38][39][40] Still, it is detectable in the kidney after oral ingestion in the rat[64] and elimination of PQQ is primarily via the urine[64] suggesting it may still play a role independent of being an enzymatic cofactor.

PQQ is not thought to play a role as a cofactor of enzymes in the kidneys like initially thought, but due to being eliminated by the kidneys and accumulating in them following oral ingestion in the rat it is still thought to play a role (perhaps as a REDOX couplet, like other mechanisms)

Edit13. Interactions with Cancer

13.1. Leukemia

PQQ has been shown to be cytotoxic to U937 leukemia cells, but not NIH3T3 nor L929 cells, in a dose-dependent manner.[133] Catalase treatment neutralized these effects, as they appear to be secondary to hydrogen peroxide production in cells which PQQ has been repeatedly shown to induce.[134] Superoxide dismutase had no effect on PQQ cytotoxicity, while glutathione or N-AcetylCysteine increased cytotoxicity 2-5fold without affecting the cells on their own (and thus working via PQQ by increasing H2O2 production form PQQ 1.5-2fold).[133] PQQ by itself decreased intracellular glutathione levels, and when glutathione was depleted (via BSO, an inhibitor of γ-glutamylcysteine synthetase) the apoptosis of cells morphed into necrosis, and this necrosis was still mediated by H2O2 due to being inhibited by catalase.[133]

Induces cell death via H2O2, and uses glutathoine to produce even more H2O2 to augment its efficacy. A depletion of glutathione induces necrosis

13.2. Melanoma

PQQ has been implicated in reducing melanogenic (melanin producing) protein expression in cultured B16 cells, where it can inhibit tyrosinase expression and reduce gene activity[135] and can prevent stimulation of tryosinase mRNA by alpha-melanocyte stimulating hormone.[136]


Edit14. Interactions with Medical Conditions

14.1. Parkinson's Disease

Parkinson's disease is known to be associated with what are known as Lewy Bodies (irregular cytoplasmic inclusions[137][138]) which are comprised of a molecule known as α-synuclein[139] which is known to damange dopaminergic neurons and is involved in the pathology of Parkinson's disease when it aggregates.[140][141] It is involved in normal physiological function (as a chaperone) when unaggregated,[142] so the process of α-synuclein aggregation itself is seen as pathological.

Pyrroloquinline quinone (PQQ) is known to bind to some of these α-synuclein peptides directly via forming a schiff base with the lysine amino acids in the peptides[14] similar to both EGCG (Green Tea Catechins) and baicalein (skullcap)[14] although baicalein seems relatively more potent.[143] This direct binding also reduces formation of truncated α-synuclein[144] (which accelerate the formation of larger aggregates[145]) and the larger protein aggregates themselves[14] by around 14.8-50% at 280µM.[144] This may indirectly reduce the cytotoxicity that is seen with large aggregates,[14] although PQQ seems to be capable of reducing cytotoxicity from pre-formed aggregates independent of the aforementioned binding.[144]

Protein aggregates tend to occur normally in the brain, and their aggregation is accelerated and seem to be central to the development of Parkinson's Disease. PQQ appears to physically bind to these proteins in vitro to prevent the aggregation, but it occurs at a very high concentration and it does not seem likely to occur with respectable potency following oral supplementation

6-hydroxydopamine (6-OHDA), a metabolite of dopamine which is known to cause oxidative damage to dopaminergic neurons and detected at higher levels in persons with Parkinson's,[146] may have its toxicity attenuated with coincubation of PQQ.[147] Oxidative neurotoxicity and DNA fragmentation induced by 6-hydroxydopamine was reduced in a concentration dependent manner with concentrations of 300nM showing efficacy, yet this protective effect was not seen with Vitamin C or Vitamin E, two other anti-oxidants tested at concentrations up to 100µM.[147]

Elsewhere in isolated neurons, the protein DJ-1 (plays roles in oxidative protection[148][149] and mutations in it underly some genetic cases of early onset Parkinson's Disease[150]) does not have its expression altered by PQQ[151] but 15µM PQQ appeared to preserve cell survival in the presence of oxidants by preserving the actions of DJ-1;[151] excessive oxidation of DJ-1 at C106 ablates its antioxidant potential[152] and PQQ appears to prevent this from occurring despite no direct binding.[151]

There may be some protective effects at the level of dopaminergic neurons with PQQ that is not related to preventing the formation of protein aggregation, and although this happens at a much more respectable (lower) concentration it is still uncertain if this applies to oral supplementation of PQQ

14.2. Alzheimer's Disease

Pyrroloquinline quinone appears to inhibit the formation of amyloid fibrils (Aβ1-42; full inhibition at 70μM PQQ[153]), and although it can also bind to α-synuclein this binding does not indirectly inhibit Aβ1-42 aggregation.[14]

and to reduce the cytotoxicity of these fibrils on neuronal cells.[154]


Edit15. Nutrient-Nutrient Interactions

15.1. Glutathione

PQQ has been shown to be cytotoxic to U937 leukemia cells, but not NIH3T3 nor L929 cells (but was observed in EL-4), in a dose-dependent manner with most significance at 20-50uM.[133] Catalase treatment neutralized these effects, as they appear to be secondary to hydrogen peroxide production in cells which PQQ has been repeatedly shown to induce.[134] Superoxide dismutase had no effect on PQQ cytotoxicity, while glutathione or N-AcetylCysteine increased cytotoxicity 2-5fold without affecting the cells on their own (and thus working via PQQ by increasing H2O2 production form PQQ 1.5-2fold).[133] PQQ by itself decreased intracellular glutathione levels, and when glutathione was depleted (via BSO, an inhibitor of γ-glutamylcysteine synthetase) the apoptosis of cells morphed into necrosis, and this necrosis was still mediated by H2O2 due to being inhibited by catalase.[133]

Glutathione can be increased by cysteine containing supplements including N-AcetylCysteine or Whey Protein

In cancer cells susceptible to PQQ's induction of H2O2, adding glutathione to the cell by consuming Cysteine-containing supplements can augment the efficacy of PQQ

Edit16. Safety and Toxicology

16.1. General

PQQ has been associated with renal tubule inflammation at the dose of 11-12mg/kg bodyweight in rats after injections, and some symptoms of both renal and hepatic toxicity are seen with injections of 20mg/kg in rats.[112][155] Acute death from PQQ injections between doses of 500-1000mg/kg bodyweight has been recorded in rats.[11][155]

11-12mg/kg bodyweight, based on rudimentary body surface area conversions, is approximately 120-131mg/PQQ daily (although injections) if extrapolated to humans.

One human study using 20mg PQQ alone or in combination with 300mg CoQ10 noted that there were no toxicological signs or symptoms associated with treatment over a 12 week period,[108] and consumption of up to 0.3mg/kg PQQ (around 20mg for a 150lb person) for one week has been noted to be safe.[30]

Chronic toxicity to the kidneys and liver may be achieved at a relatively low dose, although acute death requires a very high and unpractical dose. Until more evidence surfaces, it would be prudent to avoid superloading

16.2. Genotoxicity

In an Ames test (TA1535, TA1537, TA98, and TA100 strains), 10-5000μg PQQ per plate (without metabolic activation) and 156-5000μg per plate (with activation) has failed to show appreciable genotoxic effects.[156]

In lung fibroblasts derived from chinese hamsters, 12.5-400μg/mL (no metabolic activation) and 117.2-3750μg/mL (with activation; highest concentration being 10mM) and the latter concentration in isolated lymphocytes failed to exert appreciable genotoxic effects as assessed by structural abberations and polyploidy.[156]

The aforementioned disodium salt of PQQ has failed to acutely exert genotoxic effects in mice (up to 2,000mg/kg) as assessed by a micronucleus assay and in bone marrow erythrocytes.[156]

No genotoxiticity has been noted with the disodium salt of PQQ

Scientific Support & Reference Citations
References
HAUGE JG. GLUCOSE DEHYDROGENASE OF BACTERIUM ANITRATUM: AN ENZYME WITH A NOVEL PROSTHETIC GROUP. J Biol Chem. (1964)
Anthony C. Pyrroloquinoline quinone (PQQ) and quinoprotein enzymes. Antioxid Redox Signal. (2001)
Levels of pyrroloquinoline quinone in various foods
Noji N, et al. Simple and sensitive method for pyrroloquinoline quinone (PQQ) analysis in various foods using liquid chromatography/electrospray-ionization tandem mass spectrometry. J Agric Food Chem. (2007)
Mitchell AE, et al. Characterization of pyrroloquinoline quinone amino acid derivatives by electrospray ionization mass spectrometry and detection in human milk. Anal Biochem. (1999)
Kumazawa T, et al. Levels of pyrroloquinoline quinone in various foods. Biochem J. (1995)
Characterization of Pyrroloquinoline Quinone Amino Acid Derivatives by Electrospray Ionization Mass Spectrometry and Detection in Human Milk
Steinberg F, et al. Pyrroloquinoline quinone improves growth and reproductive performance in mice fed chemically defined diets. Exp Biol Med (Maywood). (2003)
Ikemoto K, Sakamoto H, Nakano M. Crystal structure and characterization of pyrroloquinoline quinone disodium trihydrate. Chem Cent J. (2012)
Molecular and crystal structure of PQQ (methoxatin), a novel coenzyme of quinoproteins: extensive stacking character and metal ion interaction
Rucker R, Chowanadisai W, Nakano M. Potential physiological importance of pyrroloquinoline quinone. Altern Med Rev. (2009)
Kim J, et al. Pyrroloquinoline quinone inhibits the fibrillation of amyloid proteins. Prion. (2010)
Mukai K, Ouchi A, Nakano M. Kinetic study of the quenching reaction of singlet oxygen by Pyrroloquinolinequinol (PQQH(2), a reduced form of Pyrroloquinolinequinone) in micellar solution. J Agric Food Chem. (2011)
Yoshida W, et al. Partial peptide of α-synuclein modified with small-molecule inhibitors specifically inhibits amyloid fibrillation of α-synuclein. Int J Mol Sci. (2013)
Adachi O, et al. Adduct formation of pyrroloquinoline quinone and amino acid. Biofactors. (1988)
Zhang Y, Rosenberg PA. The essential nutrient pyrroloquinoline quinone may act as a neuroprotectant by suppressing peroxynitrite formation. Eur J Neurosci. (2002)
Kasahara T, Kato T. Nutritional biochemistry: A new redox-cofactor vitamin for mammals. Nature. (2003)
Felton LM, Anthony C. Biochemistry: role of PQQ as a mammalian enzyme cofactor. Nature. (2005)
Rucker R, et al. Biochemistry: is pyrroloquinoline quinone a vitamin. Nature. (2005)
Wang L, et al. Cloning and characterization of a novel human homolog* of mouse U26, a putative PQQ-dependent AAS dehydrogenase. Mol Biol Rep. (2005)
Bauerly KA, et al. Pyrroloquinoline quinone nutritional status alters lysine metabolism and modulates mitochondrial DNA content in the mouse and rat. Biochim Biophys Acta. (2006)
Stites TE, Mitchell AE, Rucker RB. Physiological importance of quinoenzymes and the O-quinone family of cofactors. J Nutr. (2000)
The Biochemistry, Physiology and Genetics of PQQ and PQQ-containing Enzymes
Puehringer S, Metlitzky M, Schwarzenbacher R. The pyrroloquinoline quinone biosynthesis pathway revisited: a structural approach. BMC Biochem. (2008)
Flückiger R, et al. Characterization of the glycine-dependent redox-cycling activity in animal fluids and tissues using specific inhibitors and activators: evidence for presence of PQQ. Biochem Biophys Res Commun. (1993)
Flückiger R, Paz MA, Gallop PM. Redox-cycling detection of dialyzable pyrroloquinoline quinone and quinoproteins. Methods Enzymol. (1995)
Stites T, et al. Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice. J Nutr. (2006)
Pyrroloquinoline Quinone Improves Growth and Reproductive Performance in Mice Fed Chemically Defined Diets
Bauerly K, et al. Altering pyrroloquinoline quinone nutritional status modulates mitochondrial, lipid, and energy metabolism in rats. PLoS One. (2011)
Harris CB, et al. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. (2013)
Paz MA, et al. The catalysis of redox cycling by pyrroloquinoline quinone (PQQ), PQQ derivatives, and isomers and the specificity of inhibitors. Anal Biochem. (1996)
Paz MA, et al. Specific detection of quinoproteins by redox-cycling staining. J Biol Chem. (1991)
A novel coenzyme from bacterial primary alcohol dehydrogenase
Dooley DM, et al. The generation of an organic free radical in substrate-reduced pig kidney diamine oxidase-cyanide. FEBS Lett. (1987)
van der Meer RA, et al. Primary structure of a pyrroloquinoline quinone (PQQ) containing peptide isolated from porcine kidney diamine oxidase. Biochem Biophys Res Commun. (1989)
Groen BW, van der Meer RA, Duine JA. Evidence for PQQ as cofactor in 3,4-dihydroxyphenylalanine (dopa) decarboxylase of pig kidney. FEBS Lett. (1988)
van der Meer RA, Jongejan JA, Duine JA. Dopamine beta-hydroxylase from bovine adrenal medulla contains covalently-bound pyrroloquinoline quinone. FEBS Lett. (1988)
Robertson JG, et al. Spectral studies of bovine dopamine beta-hydroxylase. Absence of covalently bound pyrroloquinoline quinone. J Biol Chem. (1989)
Duine JA. PQQ in plants (and animals). Trends Biochem Sci. (1991)
Klinman JP, et al. Status of the cofactor identity in copper oxidative enzymes. FEBS Lett. (1991)
Kamata H, Hirata H. Redox regulation of cellular signalling. Cell Signal. (1999)
Kinetic study of the antioxidant activity of pyrroloquinolinequinol (PQQH2, a reduced form of pyrroloquinolinequinone) in
 
PQQ has been found in stardust or interstellar dust...or comet dust. Very interesting

_http://www.theage.com.au/articles/2004/06/18/1087245072385.html

We're all made of stardust
June 18, 2004
Page Tools

All life on this planet had its origins in stardust which probably brought the microscopic building blocks of life through tractless space to Earth billions of years ago, according to a team of German physicists.

The researchers at the Darmstadt research laboratory of Dr Franz R Krueger and the Max Planck Institute for Aeronomics in Katlengurg-Lindau said they had found traces of molecular enzymes in the tail of a comet encountered by the American Stardust probe.

The NASA probe has an onboard Cometary and Interstellar Dust Analyser (CIDA), a mass spectrometer that has been collecting information from interstellar dust particles since 1999.

The scientists said they found evidence of a co-enzyme similar to pyrroloquinoline-quinone (PQQ) that is a pre-requisite for life as we know it.

"PQQ-like co-enzymes occur in all life forms aside from archaeobacteria," said Jochen Kissel of the Robert Koch Institute.

"It is a vital link in the chain of life on Earth."

Writing in the journal Science, co-researcher Krueger, head of a private physics lab in Darmstadt, said he is convinced that it was the arrival of PQQ-laden stardust on Earth 3.6 billion years ago that spawned life on the otherwise lifeless planet.

For years scientists were puzzled by the sudden appearance of PQQ co-enzymes. The question was where the genetic makeup of PQQ co-enzymes, so while necessary for life, came from if the Earth had no life able to produce such a genetic makeup.

"It is the age-old question of which came first, the chicken or the egg," Krueger said. "The enzymes that start the process can only come into existence themselves if a genetic code already exists."

Combined with water and other factors, the co-enzymes could have spawned life in the early seas of Earth.

"The PQQ-like co-enzymes themselves come into being with the aid of cosmic rays from existing molecules on the surface of mineral particles," Kissel said.

Krueger is part of the team that developed the spectrometer aboard the NASA probe which gathers dust particles streaking through space at the speed of 20 kilometres per second.

"To this day about 4,000 tons of interstellar dust falls to Earth each year," Krueger said, "most of it vaporising in the atmosphere."

Could be an explanation for the mutagenic effects of comets.

_http://articles.chicagotribune.com/2004-06-18/news/0406180353_1_comet-probe-comet-dust-craters

Organic chemicals found on a comet may support the idea that ancient cosmic collisions helped spur the origins of life on Earth, scientists said Thursday as they presented data from a probe that passed within 147 miles of comet Wild 2 earlier this year.

The probe, called Stardust, is bringing back to Earth the first dust samples ever returned from a comet. But data and pictures published Friday also give detailed clues about the comet's anatomy that indicate it is surprisingly different from comets studied before.

Comets offer unique insights into the formation of the solar system because they contain material that has changed little since the sun and planets formed more than 4 billion years ago. They are essentially dirty snowballs, composed mostly of frozen water and dust, and they are visible only when their orbits take them near the sun. The sun's heat causes jets of dust and water vapor to burst from the comet's surface--forming the comet's tail.

Because the young Earth was too hot for many organic molecules to last for long, some experts have proposed that impacts by comets in a later period may have seeded the planet with some of life's chemical building blocks.

"We don't expect that life came from comets," said Donald Brownlee, the leading scientist of the Stardust mission. "But we do expect that the molecules used by life probably came from comets and asteroids."

That theory gained support from Stardust data analyzed by a German team led by Jochen Kissel. Their findings appear in Friday's edition of the journal Science along with three other papers on the comet probe, including one by University of Chicago scientists.

Kissel's group used instruments on the probe to analyze dust near Wild 2 and found an organic compound called PQQ that had never been detected in a comet. Researchers believe PQQ plays a key role in cell growth.

"PQQ is found in [almost] every cell of every living entity on earth," Kissel said.

In addition to its chemical findings, Stardust obtained the highest resolution photos ever taken of the solid part of a comet, called the core. The comet was riddled with craters, which scientists said indicates that Wild 2's original surface has not been burned away by the sun.

Named after the Swiss scientist who discovered it, Wild 2 (pronounced "vilt two") entered the inner realm of the solar system only recently, in 1974, after a close encounter with Jupiter changed its orbit. Only then did the comet's ancient core start losing material to the heat of the sun.

"We were expecting craters," Brownlee said. "Craters mean that some of [Wild 2's] surface is really old."

Yet the craters and structures were unlike anything seen before on the surface of comets, the researchers said.

"We were totally stunned by what we saw," Brownlee said, describing craters with almost vertical walls. "The vertical walls are amazing because if the comet were made of a powdery material, you couldn't support vertical surfaces."

Many scientists had thought of comet cores as fragile, said Claudia Alexander, project scientist at NASA's Jet Propulsion Laboratory in California. Other comets seemed so tenuous that they fell apart easily, as when comet Shoemaker-Levy 9 broke up as it approached Jupiter in 1994. But Wild 2's craters suggest its composition is more solid.

Scientists were also surprised to see that the comet had about 20 jets coming from its surface.

"We thought that there would be maybe one jet," said Benton Clark, chief scientist of space exploration systems at Lockheed Martin.
 
I started taking PQQ supplements as an experiment this week. I'm using Jarrow Formulas 20mg once a day (that was the only brand I found that didn't have rice flour or rice bran in it). I definitely feel increased energy. Almost too much. Maybe when I run out I'll get the lower dosage.

From Wikipedia:

Pyrroloquinoline quinone (PQQ) was discovered by J.G. Hauge as the third redox cofactor after nicotinamide and flavin in bacteria (although he hypothesised that it was naphthoquinone).[1] Anthony and Zatman also found the unknown redox cofactor in alcohol dehydrogenase and named it methoxatin.[2] In 1979, Salisbury and colleagues[3] as well as Duine and colleagues[4] extracted this prosthetic group from methanol dehydrogenase of methylotrophs and identified its molecular structure. Adachi and colleagues identified that PQQ was also found in Acetobacter.[5]

These enzymes containing PQQ are called quinoproteins. Glucose dehydrogenase, one of the quinoproteins, is used as a glucose sensor. Subsequently, PQQ was found to stimulate growth in bacteria.[6] In addition, antioxidant and neuro-protective effects were also found.[7]


Mitochondrial biogenesis

In 2010, researchers at the University of California at Davis released a peer-reviewed publication showing that PQQ’s critical role in growth and development stems from its unique ability to activate cell signaling pathways directly involved in cellular energy metabolism, development, and function.

Most significantly, the study demonstrated that PQQ not only protects mitochondria from oxidative stress—it promotes the spontaneous generation of new mitochondria within aging cells, a process known as mitochondrial biogenesis.[8] The implications of this discovery for human health and longevity are significant because the only other known methods proven to stimulate mitochondiral biogenesis in aging humans are intense aerobic exercise,[9] strict caloric restriction,[10] and certain medications such as thiazolidinediones[11] and the diabetes drug metformin.[12]
Activation of signaling molecules

The team of researchers at the University of California analyzed PQQ’s influence over cell signaling pathways involved in the generation of new mitochondria and found that there are three signaling molecules activated by PQQ that cause cells to undergo spontaneous mitochondrial biogenesis:[8]

PQQ activates expression of PCG-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), a “master regulator” that mobilizes cells’ response to various external triggers. It directly stimulates genes that promote mitochondrial and cellular respiration, growth, and proliferation. Its capacity to upregulate cellular metabolism at the genetic level favorably affects blood pressure, cholesterol and triglyceride breakdown, and the onset of obesity.[13]

PQQ triggers the CREB signaling protein (cAMP-response element-binding protein), which plays a pivotal role in embryonic development and growth. It also beneficially interacts with histones, proteins involved in the packaging and nuclear organization of cell DNA.[14] CREB also stimulates the growth of new mitochondria.

PQQ regulates a recently discovered cell signaling protein called DJ-1. As with PCG-1α and CREB, DJ-1 is involved in cell function and survival, has been shown to prevent cell death by combating intensive oxidative stress,[15][16] and is likely important to brain health and function. DJ-1 mutations have been conclusively linked to the onset of rare inherited forms of Parkinson’s disease and other neurological disorders.[citation needed]

Neuroprotection

PQQ is a neuroprotective compound that has been shown in a small number of preliminary studies to protect memory and cognition in aging animals and humans.[17][18] It has been shown to reverse cognitive impairment caused by chronic oxidative stress in animal models and improve performance on memory tests.[19] PQQ supplementation stimulates the production and release of nerve growth factors in cells that support neurons in the brain,[20] a possible mechanism for the improvement of memory function it appears to produce in aging humans and rats.

PQQ has also been shown to safeguard against the self-oxidation of the DJ-1 protein, an early step in the onset of some forms of Parkinson’s disease.[21]

PQQ protects brain cells against oxidative damage following ischemia-reperfusion injury—the inflammation and oxidative damage that result from the sudden return of blood and nutrients to tissues deprived of them by stroke.[22] Reactive nitrogen species (RNS) arise spontaneously following stroke and spinal cord injuries and impose severe stresses on damaged neurons, contributing to subsequent long-term neurological damage.[23] PQQ suppresses RNS in experimentally induced strokes,[24] and provides additional protection following spinal cord injury by blocking inducible nitric oxide synthase (iNOS), a major source of RNS.[25]

In animal models, administration of PQQ immediately prior to induction of stroke significantly reduces the size of the damaged brain area.[26] These observations have been compounded by the observation in vivo that PQQ protects against the likelihood of severe stroke in an experimental animal model for stroke and brain hypoxia.[22]

PQQ also affects some of the brain’s neurotransmitter systems. It protects neurons by modulating the properties of the N-methyl-D-aspartate (NMDA) receptor,[27][28] and so reducing excitotoxicity—the damaging consequence of long-term overstimulation of neurons that is associated with many neurodegenerative diseases and seizures.[29][30][31][32]

PQQ also protects the brain against neurotoxicity induced by other powerful toxins, including mercury[33](a suspected factor in the development of Alzheimer’s disease[34]) and oxidopamine[35] (a potent neurotoxin used by scientists to induce Parkinsonism in laboratory animals by destroying dopaminergic and noradrenergic neurons.[36])

PQQ prevents aggregation of alpha-synuclein, a protein associated with Parkinson’s disease.[37] PQQ also protects nerve cells from the toxic effects of the amyloid-beta protein linked with Alzheimer’s disease,[38] and reduces the formation of new amyloid beta aggregates.[39]
Cognition

PQQ has been shown to promote memory, attention, and cognition in laboratory animals.[17]

In humans, in one double-blind, placebo-controlled clinical trial conducted in Japan in 2007, supplementation with 20 mg per day of PQQ resulted in improvements on tests of higher cognitive function in a group of 71 middle-aged and elderly people aged between 40-70, who outperformed the placebo group by more than twofold in their standardized memory tests.[18] Interestingly, co-administration of the unrelated compound coenzyme Q10 (CoQ10) further improved performance on standardized memory tests when subjects also took 300 mg per day of CoQ10. No adverse effects were linked to the supplementation, and the results suggested that PQQ, especially when combined with CoQ10, can be used to improve mental status and quality of life in older patients, and help slow or prevent age-related cognitive decline in middle-age patients.

However, the study was not peer-reviewed and was published in a non-academic journal. No proper scientific study of PQQ effects on memory or cognition in humans has been conducted, as of 2013.
Cardioprotection

Damage from a heart attack, like a stroke, is inflicted via ischemic reperfusion injury. PQQ administration reduces the size of damaged areas in animal models of acute heart attack (myocardial infarction). Significantly, 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]

Researchers at the University of California at San Francisco investigated this potential, comparing PQQ with the beta blocker metoprolol—a standard post-MI clinical treatment. Independently, both treatments reduced the size of the damaged areas and protected against heart muscle dysfunction. When given together, the left ventricle’s pumping pressure was enhanced. The combination of PQQ with metoprolol also increased mitochondrial energy-producing functions—but the effect was modest compared with PQQ alone. Only PQQ favorably reduced lipid peroxidation. 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]
Supplement dosage

Despite its proposed classification as an essential nutrient,[24] no recommended daily intake of PQQ has been established.

Animal studies suggest PQQ supports healthy mitochondrial function at human equivalent doses (H.E.D.) as low as 1.44 milligrams per day,[43] but 3 milligrams per kilogram have been shown to protect rat hearts from ischemic injury.[44] The majority of human studies have used higher doses, of 10–20 mg or more. Consequently, nearly all PQQ sold as supplements in the United States range from 10–20 mg.[45][unreliable source?]
 
Mr. Premise said:
I started taking PQQ supplements as an experiment this week. I'm using Jarrow Formulas 20mg once a day (that was the only brand I found that didn't have rice flour or rice bran in it). I definitely feel increased energy. Almost too much. Maybe when I run out I'll get the lower dosage.

I've been taking the lower, 10mg dosage by Jarrow, for about a month now. There is a noticeable difference in how I'm feeling, I find. It's recommended to be taken with Ubiquinol btw, (which I was already taking). I think Jarrow makes one which combines both.
 
Ennio said:
Mr. Premise said:
I started taking PQQ supplements as an experiment this week. I'm using Jarrow Formulas 20mg once a day (that was the only brand I found that didn't have rice flour or rice bran in it). I definitely feel increased energy. Almost too much. Maybe when I run out I'll get the lower dosage.

I've been taking the lower, 10mg dosage by Jarrow, for about a month now. There is a noticeable difference in how I'm feeling, I find. It's recommended to be taken with Ubiquinol btw, (which I was already taking). I think Jarrow makes one which combines both.

Glad to hear that some of you are noticing positive effects from this! It will be interesting to see what it does to you in the long term, and if your energy levels remain higher. Atreides and I just started taking it, and will report any observations we make along the road. Following Laura's advice, we started taking it together with zinc, CoQ10 and NADH.
 
Ennio said:
Mr. Premise said:
I started taking PQQ supplements as an experiment this week. I'm using Jarrow Formulas 20mg once a day (that was the only brand I found that didn't have rice flour or rice bran in it). I definitely feel increased energy. Almost too much. Maybe when I run out I'll get the lower dosage.

I've been taking the lower, 10mg dosage by Jarrow, for about a month now. There is a noticeable difference in how I'm feeling, I find. It's recommended to be taken with Ubiquinol btw, (which I was already taking). I think Jarrow makes one which combines both.

I have been taking the 10mg dosage (with Ubiquinol) for over 3 weeks and I don't see any difference for the time being.
 
I've been taking 20mg PQQ (Doctor's Best brand) along with Coq10 and niacin (precursor to NADH) for about a month. I noticed an initial increase in energy and mood boost a few days after taking it. This is not as noticeable now. Most days I have a warm feeling in my trunk area and am less bothered by the cold weather. At night I feel very warm under the covers. There was a period of about a week when I had some pretty heavy night sweats but cutting down to 500mg niacin every other day or two stopped it. I think I may have lost a few pounds as well although I've read that niacin can kick you out of ketosis for about five hours after taking it but is then followed up by a boost in HGH.
 
The night sweats may have been a part of the flush effect from the niacin as you seem to know, Odyssey. May want to try the flush free niacin form - Inositol Hexaniacinate. If you really want to go whole hog you may want to try NADH itself. I recommend this brand of NADH.
 
Ennio said:
The night sweats may have been a part of the flush effect from the niacin as you seem to know, Odyssey. May want to try the flush free niacin form - Inositol Hexaniacinate. If you really want to go whole hog you may want to try NADH itself. I recommend this brand of NADH.

Thanks Ennio. I might try that NADH when I read more about it. As far as the niacin, I like the flush feeling. It's just the night sweats that were gross. (I take the niacin in the am.) Also, I've read that the no-flush forms of niacin don't have the same benefits of the flushing kind and can be harder on the liver. Not that I'm trying to lower my cholesterol or anything but the mood, energy, growth hormone release and detoxification effects of regular niacin are plusses in my book.
 
That's interesting. For how long are you supposed to take PQQ ? Is this the kind of supplements you want to take every day, or should you take PQQ "cures" once or several times a year ?
 
This is another of those "where does it fit?" posts as there's plenty of threads dealing with telomeres.

http://research.lunenfeld.ca/rssnews/?page=2047

Solving a longstanding mystery in cell division -- Cells do not repair damage to DNA during mitosis because telomeres could fuse together

March 20, 2014


TORONTO – The paradox of a cell that shuts down its DNA repair processes during cell division has been solved, according to research published in Science on March 20, 2014. The problem had eluded science for six decades.

“We now know why a crucial DNA-repair process shuts down just when the cell starts to divide into two daughter cells,” says Dr. Daniel Durocher, a Senior Investigator at the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital in Toronto, Canada.

Throughout most of a cell’s life, corrective mechanisms are nearly always acting to repair DNA strand breaks quickly and accurately. “DNA repair helps thwart cancer and keep the cell in top shape – it is usually all in a day’s work within each cell,” Dr. Durocher adds.

Paradoxically, the exception is at the very moment when chromosomes are most vulnerable, when they physically separate into two cells at cell division (mitosis).

Telomeres fuse if repair is forced
“A cell replicating its DNA is like making a back-up copy of your hard drive,” suggests lead author Dr. Alexandre Orthwein. “You want the copy to be exactly like the original, and you don’t want any errors to creep in during the copying process.” Dr. Orthwein is completing a post-doctoral fellowship in the Durocher lab.

Dr. Durocher and his team worked backwards. First, they determined how repair proteins failed to recognize and act on chromosome breaks during cell division. Next, they modified the repair proteins in order to impose DNA repair during mitosis, and watched what happened.

“We observed a very surprising effect,” says Dr. Orthwein. Repairing the chromosome damage during cell division caused it to be defective. The problem was traced to telomeres ̶ structures found at the end of chromosomes that protect them from erosion ̶ that began to fuse to each other when DNA repair was re-activated.

“In other words, at that moment of cell division, the cell miss-identified its own telomeres as damaged DNA, which it then ‘repaired,” Dr. Orthwein says.

This revealed telomeres as dangerous structures during mitosis, because the cells momentarily lost the ability to distinguish between damaged DNA strands and normal telomeres. “While we don’t yet know why this happens, it’s so remarkable that it tells us something fundamental about telomeres and cell division. This is forming the basis of our future work,” Dr. Durocher explains.

The finding shows that cells have a difficult choice to make during this vulnerable period of cell division, adds Dr. Orthwein. “They take the drastic action of turning off DNA repair, a process that is usually highly beneficial, to prevent chromosomes from fusing with each other by mistake.”

“We often assume that we know all the principles that guide basic processes like how cells divide,” says Dr. Jim Woodgett, Director of the Lunenfeld-Tanenbaum Research Institute. “But there is still so much to discover and this is a wonderful example of how an old conundrum was resolved by asking the right questions.”

Can this new knowledge be exploited therapeutically? Dr. Durocher adds that, “Some chemotherapy drugs such as paclitaxel work by stopping cell division. Theoretically, it may be possible to enhance the efficacy of these drugs based on our findings, but if so it’s in the future.”

The paper is entitled “Mitosis inhibits DNA double-strand break repair to guard against telomere fusions.” Other co-authors from the Lunenfeld-Tanenbaum Research Institute are Amélie Frade-Turcotte, Sylvie M. Noordermeer, Marella D. Canny, Catherine M. Brun, Jonathan Strecker, and Christina Escribano-Diaz.

Kinda spoiled it at the end there with that chemotherapy drug comment.
 
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