Pqq

[J-Rod]

I have been meaning to get this back up to encourage discussion and interest and awareness to this fascinating new topic and wonderful ingredient.

PQQ & IRISIN
EXERCISE IN A PILL?


Key points

• Pyrroloquinoline quinone (PQQ) is a normal component of foods, with nutrient and vitamin-like effects.
• PQQ promotes mitochondrial growth, enhances mitochondrial function, increases antioxidant protection while reducing inflammation and cellular damage.
• PQQ is also linked to increased production of the newly identified master hormone Irisin.
• Irisin ‘mimics’ the biological adaptations associated with exercise and is associated with increases in lean body mass and fat oxidation, with reduced body fat and appetite.
• The benefits of PQQ on mitochondrial function, coupled to an increase in Irisin, muscle mass and fat oxidation; make PQQ the perfect supplement for sports performance and the promote fat burning.










Every year supplement companies launch breakthrough ingredients that are claimed to improve fat loss, exercise performance, or health. The reality is often a little different; with very few ingredients actually living up to the marketing hype. A quick look at nutritional biochemistry of most breakthrough ingredients often reveals some fundamental flaws- that ultimately compromises the effectiveness of many commercial products. The most common include ingredients that cannot be absorbed, ingredients that do not occur in nature and are highly toxic, and ingredients that are too expensive to include at proven amounts. Even if many of the new ingredients pass these hurdles they often lack evidence they actually work in healthy humans; but that's what makes PyrroloQuinoline Quinone (PQQ) different!

PQQ has been subject of exciting new research findings. Initial investigations using animals showed incredible effects on metabolism, which more recently have been replicated in humans. A wealth of data now demonstrates the importance and benefits of PQQ, which provides nutrient and vitamin-like effects in the body (Misra et al. 2012), One of the processes improved by PQQ supplementation is the number and function of mitochondria (Chowanadisai et al. 2010). These structures form the powerhouse of body cells and are responsible for burning carbohydrate and fat for energy. When the link between PQQ and mitochondrial function was first identified, scientists soon recognized the potential for PQQ to improve conditions related to poor mitochondrial function. The first step in this process was to determine what level of PQQ supplementation was actually safe.

PQQ: Natural & Safe

Most people won’t have heard of PQQ and might even think it is some sort of unnatural chemical compound or even a pharmaceutical; both are incorrect. PQQ is in fact completely natural and is found in range of foods, with the highest concentrations in fermented soybeans (Kumazawa et al. 1995). Significant amounts of PQQ are also found in kiwi fruit, papaya and green peppers (Kumazawa et al. 1995), but staples such as bread, banana, apples and tomatoes only contain about a third the PQQ content of kiwi fruit (Kumazawa et al. 1991). Even though PQQ is efficiently absorbed by humans (Harris et al. 2010), its natural presence in the diet suggests the risk of toxicity is low. In rodents single dose oral toxicity was reported to be above 500mg PQQ per kg bodyweight (Rucker et al. 2009); equivalent to an oral bolus in excess of 35g in humans. When PQQ is consumed at super-physiological levels the kidney is at greatest risk of damage (Rucker et al. 2009). Placebo controlled safety studies in humans showed the consumption of PQQ at 20mg and 60mg per day was safe (Tsuji et al. 1988, Urakami 1994). These double-blind studies used a combination of highly sensitive clinical and functional tests to assess safety and toxicity. Neither PQQ dose adversely affected glucose, triglycerides, or lipoprotein fractions. Functional tests for liver toxicity including measures of aspartate aminotransferase and serum glutamic oxaloacetic transaminase activity, were unaltered by supplementation at 60 mg per day. To specifically address potential concerns about renal toxicity, urinary N-acetyl-β-(D)- glucosaminidase activity was assessed, as this provides a sensitive marker of kidney function and damage. PQQ supplementation maintained activity of this enzyme within the normal range. These findings and more recent studies (Harris et al. 2010), demonstrate acute PQQ intake at 20 to 60 mg per day is safe in humans.


IRISIN: Activating nature’s metabolic master switch

Early studies on PQQ administration demonstrated a role in mitochondrial growth and function (Chowanadisai et al. 2010). However, only when it was found PQQ supplementation affected several regulatory pathways associated with exercise, was it’s potential for fat loss first recognized. PQQ acts as a cellular messenger mimicking some of the most fundamental effects of exercise, ultimately increasing the body’s natural production of the hormone irisin (Rucker 2009, Kelly 2012). In humans this can be considered one of the most important effects of physical activity, as circulating irisin levels are negatively correlated with age, insulin, cholesterol, and adiponectin and positively correlated with fat free mass (i.e. muscle mass) and ghrelin (Huh et al. 2012). Based on these observations increasing irisin levels would increase energy expenditure by increasing lean body mass, increase the ability to burn fat by reducing insulin levels and reduce the risk of overeating by increasing ghrelin levels. Experts in the fat loss field universally recognize that these effects (associated with increased circulating irisin) provide the energetic basis for safe, effective and sustained fat loss (Sokolov et al. 2012, Konturek et al. 2004, Kersten 2001).

Scientists have only recently uncovered the biochemical pathways through which PQQ can product such an amazing effects. Pyrroloquinoline quinone (PPQ) stimulates phosphorylation of CREB at serine 133, activates the promoter of PGC-1alpha, and increases PGC-1alpha mRNA and protein expression (Rucker 2009, Chowanadisai et al. 2010). In turn, PGC-1alpha in muscle induces irisin release into the circulation, which exhibits a range of regulatory effects to reduce fat levels (Bostrom et al. 2012, Kelly 2012). These pathways are outlined in figure 1. Writing in the highly prestigious journal Nature Bostrom et al. (2012) reported ‘mildly increased irisin levels in the blood cause an increase in energy expenditure’, suggesting ‘this could be therapeutic for human metabolic disease and other disorders that are improved with exercise’.


[Figure 1. Dietary PQQ intake and pathway to increased circulating irisin]



The Future of Ergogenic Sports Supplementation

The antioxidant and anti-inflammatory effects of PQQ (Harris et al. 2010) suggest health benefits in conditions associated with the overproduction of free radicals and excessive inflammation. In fact as the only non-statin shown to reduce C-reactive protein levels in humans (Harris et al. 2010) PQQ is likely to have widespread applications in clinical medicine (Bostrum et al. 2012). The proven importance of PQQ for enhancing mitochondrial function (Chowanadisai et al. 2010) is already creating a huge surge in interest for fat loss and anti aging supplements. However PQQs effects on a cascade of biochemical pathways also provides the potential to increase exercise performance (Figure 1). It has already been shown that human muscle irisin expression correlates with aerobic performance (Lecker et al. 2012). These preliminary observations, coupled with irisin’s positive association with lean body mass, make PQQ an ideal supplement for both endurance and strength-trained athletes.


References
Chowanadisai et al. (2010) Pyrroloquinoline Quinone Stimulates Mitochondrial Biogenesis through cAMP Response Element-binding Protein Phosphorylation and Increased PGC-1α Expression. J Biol Chem. 2010 January 1; 285(1): 142–152.

Huh et al. (2012) FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise.

Harris et al. (2010) Pyrroloquinoline Quinone (PQQ) Nutritional Status in Humans after Oral Supplementation. FASEB J. April 2010 24 (Meeting Abstract Supplement) 540.21.

Kelly (2012) Irisin, Light My Fire. Science 336, 42-45.

Kersten (2001) Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep. 2(4):282-6.

Konturek et al. (2004) Brain-gut axis and its role in the control of food intake. J Physiol Pharmacol. 55(1 Pt 2):137-54.

Lecker et al. (2012) Expression of the Irisin Precursor FNDC5 in Skeletal Muscle Correlates with Aerobic Exercise Performance in Patients with Heart Failure. Circulation Heart Failure. Sept 20 [Epub ahead of print].

Misra et al. (2012) Pyrroloquinoline-quinone and its versatile roles in biological processes. J. Biosci. 37 313–325.

Bostrum et al. 2012 A PGC1-a-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, Vol 481, p463 -481.

Rucker et al. (2009) Potential Physiological Importance of Pyrroloquinoline Quinone. Alternative Medicine Review Volume 14, Number 3, 268 – 277.

Sokolov et al. (2012) Body composition and energy metabolism at rest. Volpr Pitan 81(2):12-7.

Tsuji T, Yamaguchi K, Kondo K, Urakami T. Nerve growth factor production accelerators and compositions for preventing or treating neuronal degeneration. US Patent 5846977; 1998.

Urakami T. Process for the preparation of pyrroloquinoline quinone. US Patent 5344768; September 6, 1994.

[J-Rod]

I believe Mr. Cooper was commenting how little the author knows. Again, rest assured that this author knows HED, is a real PHD and that we have provided and have plenty of data to support the claims of this article.

He is right that some assumptions and extrapolations are made. His comments that these are 'ridiculous extrapolations' are a personal opinion. This is a new compound, new area of research and its for the consumer to decide if the assumptions are delivered by taking the product or they can wait until the research, further research follows. It will. That is the risk you have when you make an 'innovative' formulation.

I do not know Mr. Cooper from Adam - he seems like an educated bro with a lot of clout here, however at the end of the day he is a competitor who's product line certainly makes some extraplotions from Murine Models. And that is all good if a compelling and intellectual hypothesis can be made, which I certainly feel this author does. And I put my track record on that.

We certainly have nothing to hide, never have and never will. I have had the privilege of sharing some incredibly exciting things with this industry over the past 10 + years (Beta Alanine, Creatine Orotate, Agmatine, Citrulline Malate, LCLT, Acetyl Group doning (clout) etc... etc... ect...) in this industry. We/I have faced a lot of scrutiny always, however I have never hid anything. No proprietary blends, no gimmicks and now no hype - What can I say, I called Agmatine The Holy Grail! I have always been very easy to approach, never hid behind a keyboard, talked to many of you on the phone, and always supported our products.

Not a dam things changed.

[aaronuconn]

It's an intriguing supplement for sure. I'm in for some educated bro's discussing its effectiveness in all aspects of usage.

[J-Rod]

It's an intriguing supplement for sure. I'm in for some educated bro's discussing its effectiveness in all aspects of usage.

It certainly has a wide range of applications - its ability to generate new mitochondria certainly is fascinating!

[Elliptical Envy]

Subscribed

[gchurchill]

Question: It's commonly agreed that 20mg is the correct dose for PQQ, why is this? You reference an article that mentions dosing up to 60mg, but it doesn't compare the two in terms of efficacy. What else can you tell us about dosing?

[Mr.Cooper69]

I believe Mr. Cooper was commenting how little the author knows. Again, rest assured that this author knows HED, is a real PHD and that we have provided and have plenty of data to support the claims of this article.

He is right that some assumptions and extrapolations are made. His comments that these are 'ridiculous extrapolations' are a personal opinion. This is a new compound, new area of research and its for the consumer to decide if the assumptions are delivered by taking the product or they can wait until the research, further research follows. It will. That is the risk you have when you make an 'innovative' formulation.

I do not know Mr. Cooper from Adam - he seems like an educated bro with a lot of clout here, however at the end of the day he is a competitor who's product line certainly makes some extraplotions from Murine Models. And that is all good if a compelling and intellectual hypothesis can be made, which I certainly feel this author does. And I put my track record on that.

We certainly have nothing to hide, never have and never will. I have had the privilege of sharing some incredibly exciting things with this industry over the past 10 + years (Beta Alanine, Creatine Orotate, Agmatine, Citrulline Malate, LCLT, Acetyl Group doning (clout) etc... etc... ect...) in this industry. We/I have faced a lot of scrutiny always, however I have never hid anything. No proprietary blends, no gimmicks and now no hype - What can I say, I called Agmatine The Holy Grail! I have always been very easy to approach, never hid behind a keyboard, talked to many of you on the phone, and always supported our products.

Not a dam things changed.

Lol, why did you just make a whole post about me? I've always been a fan of yours and your products. I haven't scrutinized your product at all. The writeup was posted in the supplement science section and I was questioning that specific article. I've been researching PQQ for a few years now; anything I commented on it has nothing to do with the fact that Haleo is a competitor. You can dig up my posts on AM from like a year ago if you wish.

I do not have a "product line." If you genuinely think that I can't comment on any ingredient used in a product because my viewpoint is instantly biased due to affiliation, you are welcome to do so, but don't make a post playing me off as some sort of mindless pimp to everyone else. The whole point of this section is objectivity about the science of ingredients, and that's exactly what I have done and intend to do in this section.

[neddo]

This should be interdast.

[LoudyRowdy]

Dwbd

[J-Rod]

Lol, why did you just make a whole post about me? I've always been a fan of yours and your products. I haven't scrutinized your product at all. The writeup was posted in the supplement science section and I was questioning that specific article. I've been researching PQQ for a few years now; anything I commented on it has nothing to do with the fact that Haleo is a competitor. You can dig up my posts on AM from like a year ago if you wish.

I do not have a "product line." If you genuinely think that I can't comment on any ingredient used in a product because my viewpoint is instantly biased due to affiliation, you are welcome to do so, but don't make a post playing me off as some sort of mindless pimp to everyone else. The whole point of this section is objectivity about the science of ingredients, and that's exactly what I have done and intend to do in this section.

I made a post about you because its about OATS Bro.. etc... lol. (That is for Envy)

I wanted to copy and pasta this thread again because I made reference to a product in the Supplement Science Section in the OG thread. That thread got moved to the Company Promotion Section and I felt it did not belong there.

I made reference to you because you said the author does not know **** - I am paraphrasing of course. And it is all good, really it is. I just felt it was the right thing to do was to address your comments since that thread got deleted. I do not have anything against you either. From the small amount of posts or comments of yours I have seen you conduct yourself well and articulately.

And no, I do not think your viewpoint is instantly biased. If anything I would think a creator/R & D guy would always think outside the box and look at all the possibilities always. So I am sure to some degree or another you can respect what we do as a company.

PQQ is new ingredient and Irisin a whole new area of research.

[J-Rod]

Question: It's commonly agreed that 20mg is the correct dose for PQQ, why is this? You reference an article that mentions dosing up to 60mg, but it doesn't compare the two in terms of efficacy. What else can you tell us about dosing?

I believe 20mg is accepted because of a study on humans showing that to be an effective dose on brain function. We reference the studies using 20 to 60mg showing the product is safe for consumption at that dose because safety and efficacy certainly are our goals in our recommendations.

[Mr.Cooper69]

I made a post about you because its about OATS Bro.. etc... lol. (That is for Envy)

I wanted to copy and pasta this thread again because I made reference to a product in the Supplement Science Section in the OG thread. That thread got moved to the Company Promotion Section and I felt it did not belong there.

I made reference to you because you said the author does not know **** - I am paraphrasing of course. And it is all good, really it is. I just felt it was the right thing to do was to address your comments since that thread got deleted. I do not have anything against you either. From the small amount of posts or comments of yours I have seen you conduct yourself well and articulately.

And no, I do not think your viewpoint is instantly biased. If anything I would think a creator/R & D guy would always think outside the box and look at all the possibilities always. So I am sure to some degree or another you can respect what we do as a company.

PQQ is new ingredient and Irisin a whole new area of research.

Ok, I think I may have misinterpreted what went on. I was under the impression you didn't like what I said, so you had the thread deleted and then reposted it and addressed me without my post to back it up. Now that I know that that isn't the case, I no longer have any ill feelings towards you.

As far as the content of our discussion was concerned, I wasn't just spouting off steam. I read all the citations too. For instance, Harris et al doesn't seem to reference 20-60g as a safe human dose, and that figure is higher than any safety data I've found.

Or, for example, this:

"In rodents single dose oral toxicity was reported to be above 500mg PQQ per kg bodyweight (Rucker et al. 2009); equivalent to an oral bolus in excess of 35g in humans."

That HED is in fact incorrect. The author took the rat dose (500mg/kg) and multiplied it by 70kg, as is done in a typical HED. Unfortunately, he forgot to divide by the BSA factor between rats and humans, which is ~6 in this case. So it is the equivalent of an oral bolus of 6 grams, not 35.

These are just a few things. I'm not making it up and my intention wasn't to start drama. I can PM you further corrections if you'd like. My only intention from the get-go was to get the science straight...as this is the supplement science section. Make no mistake, I appreciate the contribution and I genuinely love when a new ingredient generates discussion.

[J-Rod]

imgres-13.jpeg

Ok, I think I may have misinterpreted what went on. I was under the impression you didn't like what I said, so you had the thread deleted and then reposted it and addressed me without my post to back it up. Now that I know that that isn't the case, I no longer have any ill feelings towards you.

As far as the content of our discussion was concerned, I wasn't just spouting off steam. I read all the citations too. For instance, Harris et al doesn't seem to reference 20-60g as a safe human dose, and that figure is higher than any safety data I've found.

Or, for example, this:

"In rodents single dose oral toxicity was reported to be above 500mg PQQ per kg bodyweight (Rucker et al. 2009); equivalent to an oral bolus in excess of 35g in humans."

That HED is in fact incorrect. The author took the rat dose (500mg/kg) and multiplied it by 70kg, as is done in a typical HED. Unfortunately, he forgot to divide by the BSA factor between rats and humans, which is ~6 in this case. So it is the equivalent of an oral bolus of 6 grams, not 35.

These are just a few things. I'm not making it up and my intention wasn't to start drama. I can PM you further corrections if you'd like. My only intention from the get-go was to get the science straight...as this is the supplement science section. Make no mistake, I appreciate the contribution and I genuinely love when a new ingredient generates discussion.

So you had ill will towards me? I can't seem to get my Hanging with Mr. Cooper photo to post on here, but from your profile picture, you sure have lost your tan!

Alternative Medicine Review Volume 14, Number 3 2009
Potential Physiological Importance of Pyrroloquinoline Quinone
Robert Rucker, PhD; Winyoo Chowanadisai, PhD; Masahiko Nakano, PhD

States:

In summary, these observations taken together suggest there is no evidence of acute side effects or overt toxicity from consuming PQQ in amounts up to 60 mg per day for humans or several hundred mg per kg of diet fed to animals.

I have that and SEVERAL other full papers if you are interested in viewing them.

[Mr.Cooper69]

Attachment 5701781

So you had ill will towards me? I can't seem to get my Hanging with Mr. Cooper photo to post on here, but from your profile picture, you sure have lost your tan!

Alternative Medicine Review Volume 14, Number 3 2009
Potential Physiological Importance of Pyrroloquinoline Quinone
Robert Rucker, PhD; Winyoo Chowanadisai, PhD; Masahiko Nakano, PhD

States:

In summary, these observations taken together suggest there is no evidence of acute side effects or overt toxicity from consuming PQQ in amounts up to 60 mg per day for humans or several hundred mg per kg of diet fed to animals.

I have that and SEVERAL other full papers if you are interested in viewing them.

Haha no, but I must admit I was confused .

Anyway, the OP says 60 grams, but this says 60mg. I'm totally down with the latter, but as you can see from my calculations above, roughly 6 grams would be enough to kill a human. The devil is in the details in this case.

[J-Rod]

Attachment 5701781

So you had ill will towards me? I can't seem to get my Hanging with Mr. Cooper photo to post on here, but from your profile picture, you sure have lost your tan!

Alternative Medicine Review Volume 14, Number 3 2009
Potential Physiological Importance of Pyrroloquinoline Quinone
Robert Rucker, PhD; Winyoo Chowanadisai, PhD; Masahiko Nakano, PhD

States:

In summary, these observations taken together suggest there is no evidence of acute side effects or overt toxicity from consuming PQQ in amounts up to 60 mg per day for humans or several hundred mg per kg of diet fed to animals.

I have that and SEVERAL other full papers if you are interested in viewing them.

That indeed should state 20 to 60mg - Dam Copy and Pasta!

[J-Rod]

Dwbd

How does Driving While Brain Dead apply here in dis thread?

[haiz69]

In on this. Very interesting.

[Mmats]

Too expensive

[aaronuconn]

Too expensive

As pointed out to me in a previous thread, PQQ really isn't all that expensive.

[Elliptical Envy]

So, what's the latest on PQQ? I ordered 2 bottles of LEF PQQ 10mg caps today and I plan on adding it to the original On Point formula.

Edit - We looking at 20mg a day as the preferred dose?

[gchurchill]

At 20mg/day there's a slight, but noticeable, difference in my intervals. I'd like to give 40mg/day a try, but I'll need to order a few new bottles.

[Elliptical Envy]

At 20mg/day there's a slight, but noticeable, difference in my intervals. I'd like to give 40mg/day a try, but I'll need to order a few new bottles.

40mg/day dosing will be pretty expensive. Are you using anything else that would effect endurance? I really need to comb over those PQQ studies that Joey posted.

[J-Rod]

40mg/day dosing will be pretty expensive. Are you using anything else that would effect endurance? I really need to comb over those PQQ studies that Joey posted.

I am pretty sure I sent you all of the studies.

[J-Rod]

At 20mg/day there's a slight, but noticeable, difference in my intervals. I'd like to give 40mg/day a try, but I'll need to order a few new bottles.

There are certainly acute effects to supplementation, I do believe that long term supplementation would produce greater physiological effects....meaning staying in the 20 mg range should provide you results and be more cost effective. I am not sure that 40mg is going to be incredibly more noticeable to justify costs.

[gchurchill]

40mg/day dosing will be pretty expensive. Are you using anything else that would effect endurance? I really need to comb over those PQQ studies that Joey posted.

I've also been using Arachidonic Acid, so I'm a little unsure if it's one, the other, or both. I started AA first, and noticed more of a benefit after adding in PQQ. But dosing it at 20mg in the morning and 20mg before a workout doesn't feel any different than only 20mg in the morning.

I don't think I'll be purchasing it again.

[J-Rod]

I've also been using Arachidonic Acid, so I'm a little unsure if it's one, the other, or both. I started AA first, and noticed more of a benefit after adding in PQQ. But dosing it at 20mg in the morning and 20mg before a workout doesn't feel any different than only 20mg in the morning.

I don't think I'll be purchasing it again.

I think 20 mg is plenty from my personal experience. Aerobic energy is off the charts on this stuff and I am not using any creatine, Ctirulline Malate or Beta-Alanine - just PQQ. With all the positive properties of PQQ on health, cognition and the ergogenic properties this is a supplement I look forward to taking everyday.

[J-Rod]

Really loving the ergogenic properties of this stuff. Dosing has been just 20mg, as per a daily daily OnPoint dose and reps are up all movements and cardio is incredibly easier.

[LaViidaLocaa]

Is this supplement worth the price or just another hype?
It seems to be promising, but many supps are at first. This one seems pricey, so I am wondering if more scientific evidence has come up recently?

[J-Rod]

Is this supplement worth the price or just another hype?
It seems to be promising, but many supps are at first. This one seems pricey, so I am wondering if more scientific evidence has come up recently?

It is super pricey and may not be the best bang for your buck. I have been taking about 30 mg a day from my OnPoint servings - 3 caps twice daily. I can say that I've noticed increased performance endurance wise. At my age of 39 I also appreciate the fact that the product may fight the aging process as well.

[eatyourspinach]

Do you take it before work outs? I have been taking it for months but always after because I wasn't sure about any effects it might have on inflammation.