Recent we received this anonymous inquiry about HIV and PQQ:

This one may hit you from left field, but I landed on your website after researching mitochondrial toxicity and mutations caused by the HIV medication AZT, Ziduvodine, Lamuvidine, and Combivir. I was put on post-exposure prophylaxis, a 3 drug course and have been unwell ever since with muscular and neuropathy problems.  After extensive MRI, EMG, and 40 or 50 blood tests all being normal, I have returned to the possibility that I experienced mitochondrial damage while on those toxic medications. I am wondering if PQQ would play any role in *replacing* the damaged mitochondria with new, healthy mitochondria?  Is that even how it works with DNA and Mitochondria?  Does it die, and cycle in new healthy versions? Can new versions be created, and eventually outnumber the damaged versions?  As my current goal is to undo or replace the damage done by the drugs I was prescribed. My understanding is the damaged mitochondria can replicate with new damaged mitochondria and thus causing ongoing problems, and possible mitochondrial disease. My symptoms have gradually worsened since the medications, and match exactly with mitochondrial disease.  I guess it all comes down to whether or not damaged mitochondria can eventually be filtered out of the system entirely. This is all predicated on the assumption I don’t have a genetic birth mutation and this is drug-induced.

HIV medications and mitochondrial function antiretroviral therapy are improving the life expectancy for those with HIV infections, but there is also the potential for serious side effects associated with the  medications used for HIV treatment. The current attempts to monitor such negative drug effects have focused on mitochondrial toxicity.  For example, increased apoptosis (the process of cell death that is related to or caused by a decrease in functioning mitochondria) has been demonstrated both in vitro and in vivo to occur in association with exposure to various antiretroviral drug classes.

Currently, there are no studies that link PQQ to the amelioration of HIV drug side effects.  However, there are papers that suggest some promise for biofactors, such as resveratrol  and various bioflavonoids (e.g., J Neurovirol. 2012;18:445-55 and Molecular Medicine Reports 2011; 4: 151-155). The average life span of a cell depends on what type of cell it is. There are approximately 200 types of cells in the average adult human body. The average cell life span varies:

• A few hours for certain blood cells
• 3-10 days for intestinal absorptive cells and taste receptor cells
• About a month for skin cells
• 10-15 years for muscle cells and perhaps even longer for nerve cells

For comparison, mitochondria are normally replaced in most cells at reasonably rapid rates (days in contrast to weeks or months).  Their numbers and functional capacity can increase or be  altered in relationship by a number of factors – for example, exercise and reduced food  intake (to promote the combustion of adipose tissue) are prime factors.  Given that many of the positive effects of pyrroloquinoline quinone related to mitochondria occur by mechanisms similar to those for resveratrol and to some degree the bioflavonoids and PQQ appears to influence mitochondria by well-established pathways, analogous to current speculations regarding other biofactors, one guess might be that it could potentially be helpful. However, this would only be a guess.

Pyrroloquinoline quinine, also known as PQQ, is a redox cofactor and a polyphenolic compound usually derived in food plants. It is classified as an essential micronutrient because of its usefulness to the body. It is found in the cytoplasm of cells and helps with reduction reactions and oxidation. This compound is amazingly powerful at carrying out redox reactions, and can conduct about thirty to five thousand more cycles than the regular Vitamin C.

PQQ can be consumed as a dietary supplement to aid cellular energy production and mitochondrial health and to defend the body against oxidative stress. Its most notable aspect is the fact that it stimulates the spontaneous formation of new mitochondria in the body’s aging cells, and also triggers genes governing mitochondrial protection, reproduction, and repair. While PQQ helps the body in many different ways, here are its main benefits.

Neuroprotection

It is a strong neuroprotective compound that protects cognition and memory in aging humans. Studies conducted have shown that pyrroloquinoline quinine overturns the cognitive deterioration brought about by severe oxidative stress and helps people to perform better on memory tests. PQQ supplements stimulate nerve growth creation and discharge in neuron-supporting cells in the brain. This leads to improved memory function.

PQQ is an anti-aging defense for the top energy-exhaustive organs. Its top capacity as a superior anti-oxidant and cell signaling modulator makes it very effective in fighting age-related declines as well as degenerative diseases in the body’s most energy-intensive organs; the brain and heart.

PQQ hinders the gene known as DJ-1 from self-oxidizing. This gene leads to Parkinson’s disease if left unchecked. PQQ also prevents aggregation of alpha-synuclein and defends the nerve cells from the damaging effects of amyloid-beta protein; the compounds linked to Parkinson’s disease and Alzheimer’s disease respectively. Research shows that the mitochondria of a middle aged person and that of an old person is usually highly damaged. PQQ boosts the health of the mitochondria and reverses this situation.

PQQ hinders oxidative damage on the brain cells following ischemia-reperfusion injury (the oxidative damage and inflammation that is caused by the immediate return of nutrients and blood to tissues deprived of them by a stroke). PQQ also works effectively to protect your brain against any neurotoxicity that is induced by powerful toxins such as oxidopamine and mercury.

PQQ protects neurons by inhibiting the damaging effects of prolonged over-stimulation of neurons usually associated with seizures and neurodegenerative diseases. PQQ interacts with the brain’s neurotransmitter system in a beneficial manner. It protects the neurons by adjusting the NMDA receptor site. NMDA is a very powerful intermediary of “excitotoxicity,” a result of prolonged overstimulation of neurons linked to many neurodegenerative seizures and diseases.

Cognition

PQQ promotes attention, cognition, and memory. People who take a PQQ supplement of 20 mg every day show improved performance in enhanced memory tests than those who don’t. When PQQ is taken together with coenzyme Q10, it improves the quality of life of old people as well as their mental status. It also prevents or slows down the age-related cognitive decline that occurs among old and middle aged people.

Cardioprotection

Damage from heart attack is usually inflicted via ischemia-reperfusion injury. PQQ supplements help reduce the size of the damaged areas resulting from acute heart attack. Studies carried out showed that this healing process occurs the whether PQQ is given before or after the heart attack. The supplements help reduce the size of the damaged areas and defend against heart muscle dysfunction. This suggests that giving PQQ supplements to a heart attack victim within the initial hours of medical response can offer significant benefits to them. PQQ also helps the heart’s muscle cells to resist severe oxidative stress by enhancing and preserving mitochondrial function.

What is PQQ’s Anti-Oxidant capacity and function in Mitochondrial Health?

Mitochondria are very vulnerable to destruction from oxidative damage because they function as the main engines for almost all bioenergy production in a person’s body. Mitochondrial dysfunction is widely recognized by scientists as a major biomarker of aging. Mitochondrial DNA possesses little protection against free radical damage, and therefore depends on antioxidants for protection. PQQ’s potent free radical-scavenging ability gives the mitochondria superior antioxidant protection because of its high molecular stability and ability to transfer energy directly within the mitochondria. Its exceptional molecular stability is unlike that of other antioxidants because it allows PQQ to perform numerous electron transfers without going through molecular breakdown.

PQQ is very effective in neutralizing hydroxyl and superoxide radicals, which are the two major causes of mitochondrial dysfunction. A study conducted at The University of California at Davis showed that PQQ is between 30 to 5,000 times more effective at sustaining mitochondrial energy production (redox cycling) than other antioxidant compounds such as Ascorbic Acid.

What is PQQ’s Role in Growth and Development?

PQQ’s critical function in growth and development comes from its exceptional ability to stimulate cell signaling pathways that are directly involved in development, function, and cellular energy metabolism. It encourages the natural growth of mitochondria in the body’s aging cells (Mitochondrial Biogenesis). This process helps in improving human health and longevity. Apart from this process, the only other methods known to activate mitochondrial biogenesis in old people are strict caloric restrictions, intense aerobic exercises, and specific medications such as Metformin and Thiazolidinediones (for diabetes). PQQ is therefore a crucial compound in enhancing mitochondrial function resulting in better output for the body’s energy cells

PQQ is an essential compound that plays a critical part in the human body. Without it, a person can experience growth impairment, abnormal reproductive function, and compromised immune status. The immune system is very responsive to low amounts of PQQ and requires it just like other essential nutrients. When the body is deprived of PQQ, multiple defects occur in the body’s immune functions.

Mitochondria dysfunction has been linked to almost all killer diseases of aging, from type 2 diabetes, to Alzheimer’s disease, to heart failure. PQQ effectively stimulates mitochondria repair, reproduction, and protection. It also provides optimal defense against neural degeneration and gives powerful cardioprotection to ensure one lives a long and healthy life.

There have been a few of you concerned about pyrroloquinoline quinone and erectile dysfunction. Recently we received the following question:

…positive results in animal studies (show) relative avoidance of ischemic reperfusion injury following induced stroke in lab animals. This was due, I understand, to PQQ’s ability to block nitric oxide synthesis. This begs the question; do you think PQQ can cause male erectile dysfunction since normal function depends on adequate levels of nitric oxide?

Pyrroloquinoline quinone is a redox active nutrient that can scavenge various reactive oxygen species (ROS), such as superoxide radicals, which can act as deleterious oxidants. This is one of several aspects that make PQQ an effective anti-ischemic agent.

PQQ is unable to directly interact with nitric oxide. Research shows it doesn’t block nitric oxide synthesis, which in part addresses the concern about erectile dysfunction. Rather, pyrroloquinoline quinone’s effect on nitric oxide relates to it’s ability to reduce the levels of the major ROS derived from nitric oxide, a compound called peroxynitrite. Nitric oxide can react with superoxide radicals to form the product, peroxynitrite.

Peroxynitrite is an oxidant and nitrating agent that can severely damage a wide array of molecules in one’s cells, including DNA and proteins. With respect to PQQ, less peroxynitrite is formed, when the formation of superoxide is blocked or reduced, because of PQQ’s ability to act as an anti-oxidant.

Regrettably, there are no clinical studies that been done to date to directly address whether PQQ is effective in the treatment of Parkinson’s disease, although the assertion is sometimes made in nutritional supplement-oriented blogs and websites less scrupulous than ours. However, there are a number of basic studies that appear promising, which suggest pyrroloquinoline quinone may be beneficial in slowing or altering the progression of Parkinson’s disease.

What is known to date? In studies using experimental animal models, PQQ does interact with the neurotransmitter systems. It appears to be a neuroprotective (also see the post, PQQ, glutamate, nitric oxide and N-methyl-D-aspartic acid receptors). PQQ could potentially protect against neurotoxicity induced by compounds that promote or produce Parkinson-like symptoms in laboratory animals. Moreover, PQQ in chemical assays inhibits the aggregation of alpha-synuclein, a process that is associated with the progression to Parkinson’s disease. Pyrroloquinoline quinone also seems to protect nerve cells by blocking new amyloid beta molecular structures from forming before they can cause cellular damage akin to what is observed in Parkinson’s disease. Although these observations are promising, questions nevertheless remain regarding how direct and specific the actions of PQQ are as they relate to altering the functions of alpha-synuclein and amyloid beta, if and when they are abnormally aggregated.

If you would like to do a deeper dive on this topic you should read:

1. Kobayashi, M; Kim, J; Kobayashi, N; Han, S; Nakamura, C; Ikebukuro, K; Sode, K. Pyrroloquinoline quinone (PQQ) prevents fibril formation of alpha-synuclein. 2006 Biochemical and Biophysical Research Communications 349: 1139–44.
2. Zhang JJ; Zhang RF; Meng XK. Protective effect of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. 2009 Neuroscience Letters 464: 165–9.
3. Kim, J; Kobayashi, M; Fukuda, M; Ogasawara, D; Kobayashi, N; Han, S; Nakamura, C; Inada, M et al. Pyrroloquinoline quinone inhibits the fibrillation of amyloid proteins. Prion 4: 26–31.

The data for PQQ’s safety is excellent, at least for limited or short-term use (e.g. up to a year) in humans and longer-term use in animals. Long-term (multiple year) safety in humans remains to be assessed.  However, based on pyrroloquinoline quinone direct to market sales, it may be concluded that hundreds of individuals now take PQQ.  Some of these users tend to be aggressive about supplementation (including myself), so the chance that an interaction with PQQ may be adverse seems highly unlikely based on the lack of any published reports.

Although there are no direct studies on the potential interaction of PQQ with psychotropic drugs, several studies suggest that the idea is worth exploring.  What data that are available regarding cognition are in two animal studies and one human study (see below). The human study is well controlled and the results of the study suggest that PQQ alone or with CoQ10 may be useful for improving higher brain function. Likewise, the animal studies are supportive of this perspective.

To be very clear, not all these supplements and medicines work independently? The best answer about food supplementation and drug interaction is going to come from your personal physician and pharmacist. Although one can identify major mechanisms or even specific functions for given compounds, from a global physiological perspective, there can be cross talk between the numerous cell-signaling pathways that control cellular function and an enzyme cofactor may interact with numerous enzymes each with a specific function.

1: Takatsu H, Owada K, Abe K, Nakano M, Urano S. Effect of vitamin E on learning and memory deficit in aged rats. J Nutr Sci Vitaminol (Tokyo). 2009; 55:389-93.

2: Ohwada K, Takeda H, Yamazaki M, Isogai H, Nakano M, Shimomura M, Fukui K, Urano S. Pyrroloquinoline Quinone (PQQ) Prevents Cognitive Deficit Caused by Oxidative Stress in Rats. J Clin Biochem Nutr. 2008; 42:29-34.

3: Pyrroloquinoline quinone disodium salt improves higher brain function.  Medical Consultation and New Remedies 2011; 48(5): 519 – A Japanese food/supplement journal

PQQ is a growth factor and chemical attractant for a number of bacteria. Bacteria defined as acidobacteria and methylotrophic bacteria produce PQQ.  Acidobacteria are common to soil and methylotrophs are organisms that can use reduced one-carbon compounds, such as methanol or methane, as the carbon source for their growth.  Of potential importance to human health, PQQ is also utilized as a cofactor by bacteria that do not normally produce it as a part of their metabolism.   A good example is Escherichia coli (E. coli), the gram-negative, rod-shaped bacterium that is commonly found in the intestine. When provided PQQ, E. coli utilizes it as an enzymatic cofactor in enzymes important to glucose and alcohol metabolism. Although it seems likely that PQQ supplements may alter metabolic features of E. coli, whether PQQ influences lactobacillus and other organisms that are utilized as probiotics remains to be examined.   Making the link between PQQ and probiotic use nevertheless has potential in describing certain effects of PQQ.

With the above said, however, we would be remiss if did not also note that if PQQ has the potential of influencing probiotics. One has to also ask the question whether there is any impact on organisms, such as helicobacter pylori that has been associated with gastritis and gastric ulcers.  Only one study has been done that actually examines gut micro flora in the context of PQQ supplementation and its potential effects (Smidt et al., Does the intestinal microflora synthesize pyrroloquinoline quinone? Biofactors. 1991; 3:53-9). That study indicates that it is difficult to demonstrate PQQ synthesis by the microflora that are present in the gut.  Using a mouse as a model, there was also little change in the amounts of organisms that were reported to present in the intestine before versus after PQQ supplementation.

In summary, PQQ supplementation may be complementary to probiotic use, but more work needs to be done.  We also encourage you to read reviews that indicates the human body may respond differently to the different species and strains of probiotics (e.g., see Hakansson et al., Gut microbiota and inflammation. Nutrients. 2011; 3:637-82).

Myopathies are diseases of muscle.  Given that mitochondria play essential roles in energy regulation and production, it should come with little surprise that some myopathies arise from mitochondrial dysfunction.  Tragically, some myopathies can interfere with the ability to do even basic and simply human moments and tasks.  Myopathies also have neurological components.  With regard to mitochondria, in addition to playing a role in energy production, defects in mitochondria can affect nerve response and neuromuscular functions sufficient to influence the coordination of muscle movement.

Symptoms and types of mitochondrial myopathy

Most of the mitochondrial related myopathies are genetic in origin, although some can result from the exposure to drugs (as an example, statins used to control cholesterol production, see below), poor nutrition, or environmental factors, such as herbicides with the toxicological characteristics of inhibitors of mitochondrial function.

The more common symptoms of the mitochondrial-related myopathies are muscle weakness and the inability to control specific muscle groups to perform functions. Those who suffer may have difficulty in swallowing food or have defective speech because of the lack of control in the face and neck muscles.  In some cases, there may an inability to control muscle groups Important to eye moments.  Exercise intolerance is also a common trait; even simple movements can become exhausting. Regarding the myopathies that are genetic in origin, fortunately most are very rare in occurrence.  They range in severity from progressive weakness to early death. As may be inferred from the descriptions below, most mitochondrial myopathies are expressed early in life. Some examples include:

Kearns-Sayre syndrome – Kearns-Sayre syndrome often starts in the late teens or early twenties. The first manifestations are in the muscles associated with ocular movement eventually leading to paralysis of such muscles. There also is an abnormal buildup of pigmented material, which leads to inflammation and degeneration of the retina.  As the disease progresses, cardiac abnormalities, diabetes, and muscular coordination defects become even more apparent.  Heart arrhythmia and eventual heart block can result in very early death unless there is intervention with implantation using a cardiac pacemaker.

MERRF (Myoclonic epilepsy with ragged-red fibers) syndrome) – MERRF is rare with an estimated incidence of ~1/400,000.  The disorder is characterized by progressive myoclonic epilepsy (involuntary muscle twitching with seizures), which is often apparent at birth.  Individuals with MERRF are usually short in stature, suffer hearing loss, and have poor motor skills.

MELAS syndrome – MELAS (Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is also characterized by seizures, headaches, and episodes of paralysis.  There is often-severe cognitive impairment.

Pharmaceuticals and Myopathies

Some myopathies can also occur from exposure to drugs and toxicants.  An example of myopathy that may be drug related are those that potentially evolve or be expressed by the use of statins.  Statins are in general very safe, well tolerated and the most efficient drugs for the treatment of elevated cholesterol.  However, an adverse effect of statins is myotoxicity. Although the exact pathophysiology of statin-induced myopathies is not fully understood, important mitochondrial cofactors arise from the cholesterol biosynthesis pathway, such as CoQ10.  One possibility for a myopathy is a reduction in sufficient COQ10 to maintain normal energy production.

In addition, it has recently been shown that the use of statins is associated with the potential expression of a variety of inflammatory myopathies including polymyositis (chronic inflammation of the muscles), dermatomyositis (inflammation that occurs in both muscle and skin), and necrotizing myopathy (degradation and loss of muscle fibers). With regard to necrotizing myopathy, recent data suggest the serum of some of patients receiving statins contains an anti-HMGCR antibody. Apparently in addition to pharmacologically inhibiting the first step in cholesterol synthesis, i.e. inhibiting the enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), there is also up-regulation in the expression of autoantibodies to HMGCR, which can further alter not only cholesterol synthesis, but the synthesis of other compounds, such as CoQ10 that are important mitochondrial function.  For some patients the issue can be a very important one, particular when there is actual muscle damage or loss.  For example, anti-HMGCR autoantibodies were recently observed in 6% of patients presenting to the Johns Hopkins Myositis Center.  Among patients ages 50 years and older, over ninety percent had taken statins (Mammen et al. 2011 Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum;63:713-721).  This suggests that statins can cause or unmask an immune mediated myopathy.

Myopathies and environmental factors

Although rare, some signs of myopathy may result from the exposure to environmental factors, such as herbicides.  The active principles in some pesticides are compounds that inhibit the mitochondrial oxidative metabolism that leads to ATP production.  A good example is rotenone.  Rotenone is an odorless chemical that is used as a broad-spectrum insecticides, and pesticides. It occurs naturally in the roots and stems of several plants such as the jicama vine plant. Jícama is often cut into thin wedges and is often used in salads, fresh fruit combos, fruit bars, soups, and other cooked dishes. Although the root may be consumed, the remainder of the jicama plant is poisonous, because of the toxin, rotenone.

Can PQQ be beneficial in the treatment of certain myopathies?

The answer may be yes in many cases.  Mitochondria replicate more often than the cells in which they live.  Generally, the faster mitochondria turn over, the better. In other words, it is better to replace mitochondria before too much mitochondrial DNA damage accumulates.  Although PQQ stimulates mitochondriogenesis, it may also be assumed that the process involves in addition some degree of apoptosis (mitochondrial degradation and replacement).  Thus, turnover may be increased and to some degree the DNA in mitochondria may be spared from persisting in a damage form.

Appreciate, however, that these changes are not huge. A change as little as 5 to 15 percent in increased mitochondrial production can be dramatic from the perspective energy metabolism.  With regard to caveats, whether PQQ helps or not depends on the nature of the myopathy.  There are 600-1000 nuclear genes involved in mitochondrial assembly and in the mitochondrial genome a single circular chromosome that has about 40 genes.  This means that in many diseases wherein mitochondria may be involved, there are also numerous possibilities for disease-related mechanisms.  Increasing mitochondrial amount may be helpful.  However, the increase has the potential of carrying with it an increase in a defective gene product.

In a recent post a reader asked if a claim can be made that resveratrol and PQQ are direct opposites of each other. He cited the literature that points to pyrroloquinoline quinone’s role in early growth and the claims made that Resveratrol activates sirtuins in the absence of growth factors. The idea being that the longevity gene FOXO3 localizes in the nucleus and activates key longevity genes. He posited that research indicates pyrroloquinoline quinone might cluster around bone marrow, therefor making the leap that the mitochondria are probably bigger, whereas resveratrol mitochondria are smaller and more pervasive in muscle fiber.

Although these propositions are interesting. As a constructive criticism, the propositions do go beyond what is currently know about both compounds. For example, the data regarding cell signaling and PQQ is far from complete (e.g., it rests on less than a dozen of somewhat focused, albeit rather promising studies, done over the past ~6 years). Although mechanistic studies on resveratrol at the cellular level now extend well over a decade, there are still many details to resolve. As an example, the role of sirtuins in multiple metabolic and age-related pathways has been established and a link to resveratrol has been made, but whether resveratrol is a direct activator of such pathways (in contrast to an indirect modulator) remains unclear and the mechanisms remain poorly defined. In this regard, studies focusing on the sirtuins and PQQ have not been done, so it is difficult to make that direct comparison. Where comparisons can be made involve factors, such as PGC1-alpha (peroxisome proliferator-activated receptor gamma co activator 1-alpha) or TFAM (transcription factor A, mitochondrial), several of the many factors important to mitochondriogenesis and the programmed turnover of mitochondria, often referred to as apoptosis. The control of mitochondrial amount, shape, and size in cells is the result of a careful balance between both synthesis and
degradation (apoptosis). This point is important to appreciate. In addition to the many compounds that may be involved, which act as co-activators and activators, there is the coordination of dozens of cell signaling pathways that help to maintain the balance.

Regarding mitochondrial size, what data that are available suggest that there is no change in mitochondrial size in response to changes in PQQ dietary status (Pyrroloquinoline Quinone Modulates Mitochondrial Quantity and Function in Mice), although mitochondrial amount and number are affected. In the PQQ papers, “growth factor” is use generically to mean a naturally occurring substance capable of the stimulating, proliferation and/or differentiation of cells. It does not infer or routinely imply a change in a given cellular organelle’s size, such as mitochondria. Moreover, the reports to date do not support that the effects of resveratrol or PQQ are particular organ specific. Rather, markedly different cell types respond to PQQ and resveratrol exposure, often at the descriptive level, with a similar effect (e.g. an increase in mitochondrial amount or protection from ischemia).

Resveratrol and PQQ Summary:

Resveratrol and PQQ are among dozens of compounds that may have an influence on energy related metabolism. Do they act in opposition? There are no compelling reasons to propose that they do based on what information is available. It would not be surprising, however, that each provokes similar responses or even distinctly different ones by different mechanism or pathways.

Since pyrroloquinoline quinone is known for its growth factor qualities I wanted to put it to the test while having a little fun in the process. What you will find in the video below is two Chia Pets side by side… one continually saturated with a PQQ solution and the other continually saturated with distilled water. The resulting Chia growth for both the PQQ Chia and the control Chia were about the same during the normal growth cycle for chia seeds. The video takes place over the course of two weeks with a few minor breaks in the action due to software issues.

The experiment was very unscientific but yielded some interesting results. Both of the plants germinated around the same time. There was little difference with regards to initial plant health, the lushness of the sprouts, or growth rate. The PQQ plant was fed a solution of a 20 μM pyrroloquinoline quinone (which is not what you see in the background; that is concentrated pyrroloquinoline quinone solution, hence the reddish color). The control plant was fed distilled water.

The interesting findings came towards the end of the experiment. At the end of both plants’ life cycle, it initially appeared that the PQQ plant was beginning to die faster. The control plant still appeared to be flourishing…

Where as the PQQ plant began to thin a little and white areas began to emerge (which according to Chia.com is secondary root growth)…

However, in the final phase of the plants’ life cycle the control plant’s sprouts completely failed (but there was a visible lack of secondary growth and mildew)…

On the other hand the PQQ Chia clearly still had healthy sprouts that continued on living long past the control Chia Pet (although there is obviously a healthy amount of mildew as well; at this point the white areas are clearly not just root hairs)…

Conclusion: I don’t know… time-lapse photography is fun? Seriously though, I don’t think it is a big leap to identify PQQ as an interesting growth factor. How this translates in humans is still being studied and we will continue to report the latest findings. We really appreciate all your comments and tweets. If you have experimented with pyrroloquinoline quinone at all, please reach out and let us know what you discovered.

Recently a few readers have been curious if pyrroloquinoline quinone leads to mitochondrial biogenesis through the activation of cell signaling molecules such as AMPK. It has been purposed that when AMPK is activated it leads to the up-regulation of Nampt… leading to an increase in NAD+… which in turn can potentially activate the sirtuins. The activation of sirtuins would then lead to the up-regulation of PGC1-alpha and perhaps lead to an increase in natural mitochondrial biogenesis.

The theory is a good one, although speculative, as there are no direct studies related specifically to PQQ, sirtuins, and Nampt. In reality the process depends upon a number of factors, such as previous history (e.g., whether exercising, dieting, or consuming a high carbohydrate or high fat diet) and experimental models and environments. For a good answer to the question, one must also consider dose. Dose is always an important consideration in that over riding cell-signaling controls that were placed there for a purpose may not be that the best strategy (in many applications).

With respect to genes in the sirtuin family, most are associated with repair of DNA and help to regulate genes that undergo altered expression with aging. Dieting (food restriction) can affect (activate) Sirtuin regulatory factors (cf. Biochem Pharmacol. 2002 63:2075-80). Moreover, regulatory factors such as CREB can activate sirtuins, in particular SIRT1. In contrast, carbohydrate response-element-binding protein (ChREBP), which can be influenced by carbohydrate intake, can repress the expression of SIRT1 (cf. EMBO Rep. 2011 10.1038/embor.2011.151 [Epub ahead of print as of 7/11]). Moreover, there are many other contrasting control-related options that have been described (cf. Marcella F. & Vittorio S. Comparing and Contrasting the Roles of AMPK and SIRT1 in Metabolic Tissues. Cell Cycle. 2008 7:3669–3679).

Consequently, with regard to PQQ, if the mechanism is similar to resveratrol, as recently described by Schirmer et al. (Modulatory effect of resveratrol on SIRT1, SIRT3, SIRT4, PGC1-alpha and NAMPT gene expression profiles in wild-type adult zebra fish liver; Mol Biol Rep. 2011 [Epub ahead of print] as of 7/11), and it would be necessary to assess this process with the addition of a number of other variables. For example, the data by Schimmer and associates suggest in their animal model (Zebra fish), resveratrol did not change the mRNA levels of SIRT1 and PGC1-alpha, and decreased the expression levels of the SIRT3, SIRT4, and Nampt genes, which is somewhat different than possible chain of events we’ve purposed above.

To reiterate, the reasons for all the qualifications are their importance to interpreting effectors/modulators of cell signaling and related pathways. Consider that altering the NAD+/H ratio (e.g., because of a change in Nampt expression) can also alter the so-called energy charge of the cell (AMP/ADP/ATP ratios). An alteration in cell charge activates dozens of metabolic related pathways (cf. BioEssays 23:1112-1119; excellent review). Some of the branch points and pathways, when viewed as a linear sequence in contrast to something more complex may fit a hypothesis or may also appear to be counter intuitive without more information.