Pyrroloquinoline Quinone (PQQ)

Discussion in 'Supplements' started by narouz, Oct 18, 2015.

  1. narouz

    narouz Member

    Joined:
    Jul 22, 2012
    Messages:
    4,429
    I hadn't come across this before.
    There seems to be some controversy about it--see end of the article.
    This is from Wiki...


    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 neuroprotective effects were also found.[7]

    Mitochondrial biogenesis in mice
    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. The study demonstrated that PQQ not only protects mouse hepatocyte mitochondria from oxidative stress—it promotes the spontaneous generation of new mitochondria within aging cells, a process known as mitochondrial biogenesis.[8]

    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 mouse proteins activated by PQQ that cause cells to undergo spontaneous mitochondrial biogenesis: peroxisome proliferator-activated receptor gamma coactivator 1-alpha, cAMP response element-binding protein, and the DJ-1 protein.[8]

    Cardioprotection in rat models
    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.[9]

    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.” [10]

    Subsequent research has also demonstrated that PQQ helps heart muscle cells resist acute oxidative stress by preserving and enhancing mitochondrial function.[11]

    Radiation poisoning in mice
    In a study of gamma radiation poisoning in mice, 4mg/kg of PQQ improved 30-day survival from 2/20 to 12/20 at an 8 Gy dose.[12]

    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.[13][14] It has been shown to reverse cognitive impairment caused by chronic oxidative stress in animal models and improve performance on memory tests.[15] PQQ supplementation stimulates the production and release of nerve growth factors in cells that support neurons in the brain,[16] 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.[17]

    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.[18] 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.[19] PQQ suppresses RNS in experimentally induced strokes,[20] and provides additional protection following spinal cord injury by blocking inducible nitric oxide synthase (iNOS), a major source of RNS.[21]

    In animal models, administration of PQQ immediately prior to induction of stroke significantly reduces the size of the damaged brain area.[22] 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.[18]

    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,[23][24] and so reducing excitotoxicity—the damaging consequence of long-term overstimulation of neurons that is associated with many neurodegenerative diseases and seizures.[25][26][27][28]

    PQQ also protects the brain against neurotoxicity induced by other powerful toxins, including mercury[29](a suspected factor in the development of Alzheimer's disease[30]) and oxidopamine[31] (a potent neurotoxin used by scientists to induce Parkinsonism in laboratory animals by destroying dopaminergic and noradrenergic neurons.[32])

    PQQ prevents aggregation of alpha-synuclein, a protein associated with Parkinson's disease.[33] PQQ also protects nerve cells from the toxic effects of the amyloid-beta protein linked with Alzheimer's disease,[34] and reduces the formation of new amyloid beta aggregates.[35]

    Controversy
    Although Nature Magazine published the 2003 paper by Kasahara and Kato which essentially stated that PQQ was a new vitamin, they also subsequently published, in 2005, an article by Chris Anthony and his colleague L.M. Fenton of the University of Southhampton which states that the 2003 Kasahara and Kato paper drew incorrect and unsubstantiated conclusions.[36] On his website,[37] Anthony discusses the Nature Magazine publications:

    When I pointed out to the journal Nature that their high reputation was being used to justify investments of millions of dollars in the development of PQQ as a vitamin, they investigated the original paper, agreed with our objections and published our argument against it (Felton & Anthony, Nature Vol. 433, 2005). They also published (alongside ours) a paper by Rucker disagreeing with the conclusions of Kasahara and Kato on nutritional grounds, concluding “that insufficient information is available so far to state that PQQ uniquely performs an essential vitamin function in animals”.

    Anthony further states on his website that "No mammalian PQQ-containing enzyme (quinoprotein) has been described" and that PQQ therefore cannot be called a "vitamin". The latter statement is an exaggeration, since there is one mammalian enzyme which appears to use PQQ as a cofactor:[38]
     
  2. OP
    narouz

    narouz Member

    Joined:
    Jul 22, 2012
    Messages:
    4,429
    I saw this, about PPQ, on the Life Extension site,
    so...read critically.
    As I said, I hadn't heard about this quinone
    (if indeed it is one...seems there may be some argument about this).


    http://www.lifeextension.com/magazine/2011/2/generate-fresh-mitochondria-with-pqq/page-01


    Generate Fresh Mitochondria with PQQ
    Scientists Discover the “Other CoQ10”
    February 2011
    By Perry Marcone

    Generate Fresh Mitochondria with PQQ
    In 1983, Life Extension® introduced a relatively little-known compound called coenzyme Q10. Our review of the literature back then had unearthed data confirming its power to boost the health and energy output of the mitochondria.

    Today, scientists recognize mitochondrial dysfunction as a key biomarker of aging.1-6 To take one instance, researchers have recorded evidence of 50% more mitochondrial damage in the brain cells of humans over 70 compared to middle-aged individuals.7 Mitochondrial dysfunction and death are now definitively linked to the development of virtually all killer diseases of aging, from Alzheimer’s and type 2 diabetes to heart failure.8-11

    The good news is that mitochondrial dysfunction can be reversed.12 The scientific literature is now filled with studies documenting the therapeutic power of CoQ10 to thwart degenerative disease by boosting mitochondrial health and bioenergetic (energy-producing) capacity.13-16

    The latest advance in the area of mitochondrial bioenergetics is the coenzyme pyrroloquinoline quinone or PQQ.

    PQQ’s critical role across a range of biological functions has only gradually emerged. Like CoQ10, it is a micronutrient whose antioxidant capacity provides extraordinary defense against mitochondrial decay.

    But the most exciting revelation on PQQ emerged early in 2010, when researchers found it not only protected mitochondria from oxidative damage—it stimulated growth of fresh mitochondria!17

    In this article, you will learn of this novel coenzyme’s ability to combat mitochondrial dysfunction. You will find out how it protects the brain, heart, and muscles against degenerative disease. You will also discover its potential to reverse cellular aging by activating genes that induce mitochondrial biogenesis—the spontaneous formation of new mitochondria in aging cells!

    PQQ: A Breakthrough in Cellular Anti-Aging
    PQQ is ubiquitous in the natural world. Its presence in interstellar stardust has led some experts to hypothesize a pivotal role for PQQ in the evolution of life on Earth.18 It has been found in all plant species tested to date. Neither humans nor the bacteria that colonize the human digestive tract have demonstrated the ability to synthesize it.19 This has led researchers to classify PQQ as an essential micronutrient.20

    PQQ’s potential to stimulate mitochondrial biogenesis was foreshadowed by repeated early findings indicating its central role in growth and development across multiple forms of life.

    It has been shown to be a potent growth factor in plants, bacteria, and higher organisms.21,22 Pre-clinical studies reveal that when deprived of dietary PQQ, animals exhibit stunted growth, compromised immunity, impaired reproductive capability, and most importantly, fewer mitochondria in their tissue. Rates of conception, the number of offspring, and survival rates in juvenile animals are also significantly reduced in the absence of PQQ.23-25 Introducing PQQ back into the diet reverses these effects, restoring systemic function while simultaneously increasing mitochondrial number and energetic efficiency.

    Optimal Mitochondrial Defense
    As the primary engines of almost all bioenergy production, the mitochondria rank among the physiological structures most vulnerable to destruction from oxidative damage. PQQ’s formidable free radical–scavenging capacity furnishes the mitochondria with superior antioxidant protection.

    At the core of this capacity is an extraordinary molecular stability.30 As a bioactive coenzyme, PQQ actively participates in the energy transfer within the mitochondria that supplies the body with most of its bioenergy (like CoQ10).

    Unlike other antioxidant compounds, PQQ’s exceptional stability allows it to carry out thousands of these electron transfers without undergoing molecular breakdown. It has been proven especially effective in neutralizing the ubiquitous superoxide and hydroxyl radicals.31 According to the most recent research, “PQQ is 30 to 5,000 times more efficient in sustaining redox cycling (mitochondrial energy production) . . . than other common [antioxidant compounds], e.g. ascorbic acid.”21 A consistent finding in the scientific literature is that nutrients like PQQ provide more wide-ranging benefits than conventional antioxidants the general public relies on.

    Anti-Aging Armor for the Most Energy-Intensive Organs
    PQQ’s dual capacity as a cell signaling modulator and a superior antioxidant renders it optimally effective in combating degenerative disease and age-related declines in the body’s most energetic organs: the heart and brain.

    The revelation of its ability to favorably affect system-wide cell development, metabolism, and mitochondrial biogenesis affords an explanation for a wealth of data on its neuroprotective and cardioprotective benefits.

    Neuroprotection
    PQQ has been shown to optimize health and function of the entire central nervous system. It reverses cognitive impairment caused by chronic oxidative stress in pre-clinical models, improving performance on memory tests.32 It has also been shown to safeguard the “Parkinson’s disease gene,” DJ-1, from self-oxidation—an early step in the onset of disease.33

    Reactive nitrogen species (RNS), like reactive oxygen species, impose severe stresses on damaged neurons.34 They arise spontaneously following stroke and spinal cord injuries and have been shown to account for a substantial proportion of subsequent long-term neurological damage. PQQ suppresses RNS in experimentally induced strokes.35 It also provides additional protection by blocking gene expression of inducible nitric oxide synthase (iNOS), a major source of RNS, following spinal cord injury.36

    PQQ powerfully 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.37 Given immediately before induction of stroke in animal models, PQQ significantly reduces the size of the damaged brain area.38

    PQQ also interacts in a beneficial manner with our brain’s neurotransmitter systems. In particular, PQQ protects neurons by modifying the important NMDA receptor site.39,40 NMDA is a powerful mediator of “excitotoxicity,” a response to long-term overstimulation of neurons that is associated with many neurodegenerative diseases and seizures.41-43 PQQ also protects against neurotoxicity induced by other toxins, including mercury.44,45

    WHAT YOU NEED TO KNOW: PQQ
    Mitochondrial dysfunction has been definitively linked to virtually all killer diseases of aging, from Alzheimer’s disease and type 2 diabetes to heart failure.
    Researchers have recorded evidence of greater mitochondrial damage in the brain cells of humans over 70 compared to those in their early 40s.
    Many scientists believe mitochondrial longevity determines overall longevity.
    A next-generation coenzyme is being introduced called pyrroloquinoline quinone or PQQ that has been shown to induce mitochondrial biogenesis—the growth of new mitochondria in aging cells.
    While CoQ10 optimizes mitochondrial function, PQQ activates genes that govern mitochondrial reproduction, protection, and repair.
    PQQ also affords potent cardioprotection and defense against neuronal (brain) degeneration.
    Published studies show that 20 mg of PQQ plus 300 mg of CoQ10 may reverse age-related cognitive decline in aging humans.
    A mounting body of evidence points to PQQ as a potent intervention in Alzheimer’s disease and Parkinson’s disease. Both are triggered by accumulation of abnormal proteins that initiate a cascade of oxidative events resulting in brain cell death. PQQ prevents development of a protein (alpha-synuclein) associated with Parkinson’s disease.46 It also protects nerve cells from the oxidizing ravages of the amyloid-beta protein linked with Alzheimer’s disease.47 A 2010 study revealed that PQQ could prevent formation of amyloid beta molecular structures.48

    PQQ has also been shown to protect memory and cognition in both aging animals and humans.49,50 It stimulates production and release of nerve growth factor in cells that support neurons in the brain.51 This may partially explain why PQQ supplementation of aging rats resulted in marked improvement of their memory function.49

    In humans, supplementation with 20 mg per day of PQQ resulted in improvements on tests of higher cognitive function in a group of middle-aged and elderly people.50 These effects were significantly amplified when the subjects also took 300 mg per day of CoQ10.

    Mitochondrial Function and Longevity: The Definitive Link
    In cell biology, mitochondria are unique among other cellular components in one vital aspect: they possess their own primitive DNA, distinct from the DNA housed within the cell nucleus that you normally think of as the building block of all living organisms.

    Mitochondrial DNA closely resembles bacterial DNA, the result of an evolutionary legacy.55 Biologists believe that at one time our mitochondria existed as separate, highly energetic organisms. Our primordial ancestor cells aggressively engulfed and incorporated these “proto-mitochondria” into their own internal structure. This furnished our cellular progenitors with two powerful evolutionary advantages: it harnessed the ability of proto-mitochondria to produce vast quantities of energy from oxygen—and served to boost cellular longevity.

    This simple fact has profound implications for the science of anti-aging.

    Why? You already know that cells in your body have the capacity to divide and replicate themselves owing to the presence of nuclear DNA. If mitochondria possess their own DNA, it follows that they should also have the ability to replicate themselves and increase their number within a single human cell.

    This turns out to be the case: human cells may house anywhere from 2 to 2,500 mitochondria,56-58 depending on tissue type, nutrition, antioxidant status, and other factors. Put differently, one cell may contain over 1,000 times more mitochondria than another.

    The more high-functioning mitochondria in your body, the greater your overall health and longevity. This is no longer a matter of conjecture. A growing number of cell biologists now espouse the theory that mitochondrial number and function determine human longevity.59-61

    The problem is that the scientifically validated methods available to spontaneously increase the number of new mitochondria in our aging bodies are exceedingly difficult. To date, the only known ways to reliably stimulate mitochondrial biogenesis—sustained calorie restriction or strenuous physical activity—are far too rigorous and impractical for most aging individuals.

    A nutrient with the power to safely trigger mitochondrial biogenesis would naturally mark an extraordinary advance in the quest to halt and reverse cellular aging.

    PQQ has emerged as that nutrient.

    Cardioprotection
    As with stroke, damage in heart attack is inflicted via ischemia-reperfusion injury. Supplementation with PQQ reduces the size of damaged areas in animal models of acute heart attack (myocardial infarction).52 This occurs whether the supplement is given before or after the ischemic event itself.

    To further investigate this potential, researchers at the VA Medical Center at UC-San Francisco compared PQQ with metoprolol, a beta blocker that is standard post-MI clinical treatment. Given alone, both treatments reduced the damaged areas’ size and protected against heart muscle dysfunction. When they were given together, the left ventricle’s pumping pressure was enhanced. The combination also increased mitochondrial energy-producing functions—but the effect was small compared with PQQ alone! And only PQQ favorably reduced lipid peroxidation. The remarkable conclusion: “PQQ is superior to metoprolol in protecting mitochondria from ischemia/reperfusion oxidative damage.”53

    Subsequent research from the same team has demonstrated that PQQ helps heart muscle cells resist acute oxidative stress.54 The mechanism? Preserving and enhancing mitochondrial function.

    Why Your Mitochondria Are Highly Exposed to Lethal Mutation
    Cell aging occurs as each cell’s ability to reproduce itself inexorably declines. This decline is in turn associated with the gradual degradation and destruction of the DNA complex.

    Overlooked in this process is the equally important role of the mitochondria’s robust ability to reproduce as you age.

    Just as degradation of the cellular DNA complex ultimately leads to senescence and death, degradation of the mitochondrial DNA complex leads to the death of the mitochondria and the ultimate extinction of the cell—and the “host” organism.

    This death spiral of genetic degradation is accelerated in the mitochondria by the very physiological function they must perform. As the nuclear generators responsible for almost all bioenergetic production, mitochondria are the site of enormous oxidative activity. A nearly incalculable number of electrons are constantly flowing within the mitochondria, throwing off an equally enormous number of free radicals. This makes them highly vulnerable to biochemical insults.

    There is an additional threat, as scientists have discovered over the past several decades: relative to nuclear DNA, mitochondrial DNA possesses few defenses against free radical damage.62,63

    Cellular DNA is protected by numerous “guardian”proteins (histones and repair enzymes) that act to blunt the impact of free radicals. No such repair systems exist to protect mitochondrial DNA.62,63

    Cellular DNA also enjoys superior structural defenses. It is housed within a protective double-membrane that separates it from the rest of the cell. This double-membrane is complemented by a dense matrix of filament proteins called the nuclear lamina, a kind of hard shell casing to further buffer DNA from external impacts.

    By comparison, mitochondrial DNA is left almost entirely exposed: it attaches directly to the inner membrane where the mitochondria’s electrochemical furnace rages continuously, generating an enormous volume of toxic reactive oxygen species.

    Accordingly, mitochondrial DNA mutates at a much higher rate than cellular DNA.64 When you consider that the mitochondria supply at least 95% of the energy required for all physiological processes in your body, the need to maintain the integrity of mitochondrial DNA takes on even greater urgency. All aging humans should take every step to safeguard the genes that regulate healthy mitochondrial proliferation from lethal mutation. This is supported by an abundance of scientific studies linking genetic mutation within the mitochondria to human aging.65-67

    PQQ’s extraordinary antioxidant capacity represents a powerful new intervention that may effectively reinforce the mitochondria’s limited defenses.

    Summary
    Mitochondrial dysfunction has been definitively linked to virtually all killer diseases of aging, from Alzheimer’s disease and type 2 diabetes to heart failure.

    Researchers have recorded evidence of greater mitochondrial damage in the brain cells of humans over 70 compared to those in their early 40s. The health and function of these cellular energy generators is now considered so vital that many scientists believe mitochondrial longevity determines overall longevity in aging humans.

    In a revolutionary advance, an essential coenzyme called pyrroloquinoline quinone or PQQ has been shown to induce mitochondrial biogenesis—the growth of new mitochondria in aging cells!

    While CoQ10 optimizes mitochondrial function, PQQ activates genes that govern mitochondrial reproduction, protection, and repair. PQQ also affords potent cardioprotection and optimal defense against neuronal degeneration. Published studies show that 20 mg of PQQ plus 300 mg of CoQ10 may reverse age-related cognitive decline in aging humans.

    PQQ Activates Signaling Molecules
    A team of researchers at the University of California decided to analyze PQQ’s influence over cell signaling pathways involved in the generation of new mitochondria.17

    Their work, published in 2010, led to several extraordinary discoveries.

    They found 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. Cells undergo spontaneous mitochondrial biogenesis through the effects of three signaling molecules activated by PQQ:

    PQQ activates expression of PCG-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha). PCG-1α is a “master regulator” that mobilizes your cells’ response to various external triggers. It directly stimulates genes that enhance mitochondrial and cellular respiration, growth, and reproduction. Its capacity to upregulate cellular metabolism at the genetic level favorably affects blood pressure, cholesterol and triglyceride breakdown, and the onset of obesity.26

    PQQ triggers a signaling protein known as CREB (cAMP-response element-binding protein). CREB plays a pivotal role in embryonic development and growth. It also beneficially interacts with histones, molecular compounds shown to protect and repair cellular DNA.27 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 intrinsically involved in cell function and survival. It has been shown to prevent cell death by combating intensive antioxidant stress28,29 and is of particular importance to brain health and function. DJ-1 damage and mutation have been conclusively linked to the onset of Parkinson’s disease and other neurological disorders.

    These findings shed light on the results of prior studies where a PQQ deficiency in juvenile mice, for example, resulted in elevated plasma glucose concentrations, a 20-30% reduction in the number of mitochondria in the liver, and consequent impairment in oxygen metabolism.23 These are hallmark indicators of mitochondrial dysfunction. Additional animal models also suggested significant alterations in mitochondrial numbers.25 Taken together, these results confirm PQQ’s power to significantly boost mitochondrial number and function—the key to cellular anti-aging and longevity.

    If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at
    1-866-864-3027.

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    [/i]
     
  3. NathanK

    NathanK Member

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    Its good stuff. Same family as K2 and CoQ10
     
  4. Parsifal

    Parsifal Member

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    I believe I've read that Peat prefers other quinones?
     
  5. OP
    narouz

    narouz Member

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  6. Agent207

    Agent207 Member

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    I use to take a supplement with 100mg CoQ10 and 10mg PQQ 3 days a week. For what I researched seems best taken without NAC, so I take the NAC the other 3 days.
     
  7. NathanK

    NathanK Member

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    Not a fan of NAC, but I bet that combo would work well with some MB and/or light
     
  8. TreasureVibe

    TreasureVibe Member

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    Any proponents of PQQ?
     
  9. aussiebaldguy

    aussiebaldguy Member

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    rather eat food with it in it

    but seems hard to come by
     
  10. shine

    shine Member

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    I have been taking 10mg for some days now, the first dose had a very rejuvenating effect. Felt more energetic and the lights got turned on in my brain. Also felt like some huge ROS reduction, like taking a big dose of liposomal vitamin C. I will continue taking it, but will probably cycle it.
     
  11. ddjd

    ddjd Member

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    NAC is highly anti thyroid. not a good idea at all
     
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