Okay…you're probably thinking…PQQ. No way I'm taking that.
Granted, it's not gliding off the tongue and not many people know about it…yet.
PQQ is one of our top 3 health hacks (CBD isolate, lactoferrin, and PQQ) available with ridiculous safety.
Our dive into the Top 10 Tools for Mitochondria is what spurred our initial interest and just wait till you see why!
It gets to the root of what drives aging and aging-related diseases!
We'll dive into these areas:
- A quick intro to PQQ
- Why mitochondria is the place to focus for health and longevity
- PQQ and mitochondria
- PQQ and the brain
- PQQ and the heart
- PQQ and metabolism
- PQQ and disease
- PQQ and longevity
- Practical questions on PQQ
This just scratches the surface.
We can't go into our standard 20 page deep dives but we'll hit the highlights knowing there we can find research on almost every issue you can think of. After all, we're talking about our body's power plants!
Let's get started!
A quick intro to PQQ
PQQ has been found on asteroids…in fact, it may be part of the alchemy that spread life throughout the universe.
Either way, it was quickly taken up by all life forms starting with microbes like bacteria and fungi.
Almost given vitamin status for humans, there's one thing clear…it's definitely a vitamin for bacteria and that's the fascinating intersection for us.
PQQ is novel among biofactors that are not currently accepted as vitamins or conditional vitamins.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533503/
When PQQ is depleted, a host of ailments occur across almost all life forms including us.
We can't look at a pathway or issue and not see an improvement from PQQ (assuming there's research).
This is almost unheard of and it's why PQQ is part of our Triumverate (with CBD isolate and lactoferrin).
At its core, PQQ is a critical component for bacteria.
It allows bacteria to process their food (glucose) in anaerobic (no oxygen) environments (hence the asteroid habitat):
Of the bacterial enzymes for which PQQ serves as a cofactor, most are glucose or alcohol dehydrogenases.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533503/
We'll get into specifics below but how can PQQ have such a foundational effect on us as humans?
Hello, mitochondria!
PQQ and mitochondria
Check out Chris Palmer's book, Brain Energy. Basically, it slow-walks the connections between our energy producers called mitochondria (metabolism) and ALL mental health.
All health really and longevity to boot!
Here's the trick…our mitochondria are actually ancient bacteria that we took hostage (or coaxed??) to make our cellular energy. They power EVERYTHING you're doing.
If they're not running well, we suffer. As we age or with illness, they deteriorate in function. They even have their own DNA separate from ours and it's not great at error-correction (unlike ours).
From a 40,000 foot view, PPQ is a lifeline to our mitochondria:
Through nutritive and environmental exposures, PQQ affects essential biological processes, influencing mitochondriogenesis, reproduction, growth and aging.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533503/
That's essentially:
- Creating new mitochondria (mitochondriogenesis)
- Increasing mitochondria efficiency
- Removing faulty mitochondria (call mitophagy)
Check out our Mitochondria Rescue review to learn why this is so important.
There are big players in this pathway which will come up so we should introduce them:
- PGC–1α - drives new mitocondria
- NRF–1 and 2, TFAM - improved function
- Parkins and Pink - removal of bad mitochondria
PQQ drives all of these for bacteria!
The net effect…
PQQ not only protects mitochondria from oxidative stress but also promotes mitochondrial biogenesis27. Dietary supplementation of PQQ improves mitochondrial amounts and lipid metabolism in rats28 and has been shown to improve respiratory quotients by increasing the mitochondrial numbers and function in mice2
https://www.nature.com/articles/s41514-022-00083-0
Just a head's up…mitochondria are the weakest link for biological function in ALL animals…including us.
This is great and all but how does it actually translate? We're not bacteria. Or are we (health-wise)??
Let's first zero in on the most energy-hungry areas of the body (lots of mitochondria). We'll start up North.
PQQ and the brain
The brain uses 20% of our total body's energy even though it's a fraction of total weight.
Let's zoom through a range of important attributes with PQQ:
- Brain function with age
- Parkinson's
- Dementia
- Traumatic brain injury
- Neurogenesis (repair, growth)
- Brain cancer
- Mental health
Just a sampling if you will!
Brain function with age
PQQ and mitochondria decline as we age (more on that later). So…
Study demonstrates that supplementation of PQQ disodium salt is useful in improving memory, attention, judgment, and cognitive function, in middle-aged to elderly population, who feel they have become more forgetful because of aging.
https://pubmed.ncbi.nlm.nih.gov/34415830/
That's a "randomized, double-blind, placebo-controlled, parallel-group clinical investigation"
What about neurodegenerative diseases?
Parkinson's
There's a known issue with mitochondria function (and resulting iron overload) with Parkinson's:
Parkinson’s disease (PD) is known as a mitochondrial disease. Some even regarded it specifically as a disorder of the complex I of the electron transport chain (ETC).
https://www.frontiersin.org/articles/10.3389/fnmol.2021.797833/full
Complex I is the first chain of energy production in mitochondria (like a conveyor belt).
And PQQ?
PQQ could prevent mitochondrial dysfunction by promoting mitochondrial biogenesis and regulating mitochondrial fission and fusion, which might contribute to its neuroprotective effect in PD models.
https://www.sciencedirect.com/science/article/abs/pii/S0304394018306372
Check out our deep dive on Parkinson's and really zoom in on dopamine rescue.
What about dementia?
Dementia
First, some of the telltale signs of dementia, are the fishing wire-like amyloid beta tendrils:
The fibril formation of mouse prion protein in the presence of PQQ was dramatically prevented. Similarly, the fibril formation of amyloid β (1–42) also decreased.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2850417/
In our dementia review, we go deeper into how these are actually immune players.
In mice genetically bread to get their equivalent of Alzheimer's, PQQ, and low dose lithium:
The results showed that Li3PQQ at a relative low dose (6 and 12 mg/kg) exhibited more powerful effects in restoring the impairment of learning and memory, facilitating hippocampal long-term potentiation, and reducing cerebral amyloid deposition and phosphorylated tau level in APP/PS1 transgenic mice
https://pubmed.ncbi.nlm.nih.gov/25018109/
What about TBI?
Traumatic brain injury
Resolving the inflammatory firestorm following brain injury is critical and interesting research is looking at PQQ on this front.
First, the technical jargon in how PQQ affects key immune responders to TBI:
We found apparent expression upregulation of β-1,4-GalT-I and -V after PQQ was systemically administered.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303106/
The translation??
In summary, our experiment established that PQQ might play an important role in recovery post-TBI.
This is one of many studies. Let's go broader though.
Mental health
We have deep dives on facets affected by PQQ which are directly tied to mental health:
Again, Chris Palmer's book puts mental health squarely at the doorstep of mitochondrial function.
So…
the results of the Profile of Mood States-Short Form revealed that all six measures of vigor, fatigue, tension-anxiety, depression, anger-hostility and confusion were significantly improved following PQQ administration compared with scores for those measures before administration of PQQ.
https://www.ffhdj.com/index.php/ffhd/article/view/81
Goodness.
We love this study because it also gives us the 8 week marker as a basis and shows no tolerance.
The more interesting piece was its effect on circadian rhythm and sleep:
Furthermore, the changes in these global scores were correlated with changes in the cortisol awakening response (R = -0.55), i.e., the effects of PQQ on improvement of sleep quality are supported by a biomarker.
Cortisol drives our daily cycle (peaks in the morning and drops at night…ideally).
Check out our Sleep Rescue review to understand why this is so important.
Sleep loss looks just like extreme anxiety on MRI scans.
We look forward to much more research but if Chris Palmer is correct, the full spectrum is at play here.
Let's turn to the other energy hungry area…the heart.
PQQ and the heart
Keep in mind that mitochondria process cholesterol into steroidal hormones (see estrogen, progesterone, and testosterone guides).
More importantly, mitochondria are at the heart of…heart failure!
Mitochondrial dysfunction is a key feature of systolic heart failure and is thought to contribute to heart failure progression through both impaired high energy phosphates production and increased production of reactive oxygen species (ROS).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4088994/
Which begs the question…
Pyrroloquinoline quinone can prevent chronic heart failure by regulating mitochondrial function
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369269/
Front page news, right??
It's a litany of effects with positive outcomes on the heart:
In vivo and in vitro, PQQ pretreatment improved pressure overload-induced cardiac remodeling and cell hypertrophy, thus preventing the occurrence of CHF.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369269/
Goodness…in the live body, PQQ:
- Balanced the load on heart function
- Prevented the overgrowth of heart tissue that occurs from failure
The net effect of this "calming" activity?
These factors can prevent mitochondrial dysfunction, thereby reducing cardiac damage caused by pressure overload and preventing the occurrence of CHF.
Just to be clear, CHF is congestive heart failure. Kind of a big deal.
Check out the research on PQQ and heart inflammation from that which can't be named:
https://journals.sagepub.com/doi/full/10.1177/1934578X221080929
Let's head down south.
PQQ and the gut
The bacteria that make up our gut (the microbiome) are all the rage for health these days.
Since PPQ is a bacteria vitamin essentially, what does it do there? Can it drive bad bacteria growth as well?
This is soooo important and one of our favorite studies.
Researchers looked at PQQ supplementation for pigs with e-coli overgrowth:
These results suggest that dietary supplementation with PQQ can effectively alleviate jejunal mucosal inflammatory injury by inhibiting NF-κB pathways and regulating the imbalance of colonic microbiota in piglets challenged with E. coli K88.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396494/
Let's break this down because it's too cool.
PQQ given to pigs with e coli overgrowth in their gut:
- Reduced gut inflammation
- Supported the gut barrier (mucus formed by good bacteria)
- "Balanced" gut bacteria make-up
The last one is critical. PQQ is able to selectively support bacteria that are beneficial to our gut function.
It's hard to really square how it's able to do this other than to suppose that we co-evolved with PQQ over millennium.
The gut barrier is key to auto-immune, heart and brain health, plus system-wide inflammation states!
Check out reviews on gut barrier or gut inflammation to learn why they're so important.
Fine…what about general disease states. We'll pick some big ones.
PQQ and disease
We've covered some of the leading killers already (heart, dementia, that which can't be named, etc.).
Let's quickly look at:
- Diabetes and metabolism in general
- Liver disease
- Auto-immune
- Strokes
- Fertility??
The big one first.
Diabetes and metabolism in general
Mitochondria are literally the band-leaders for all things metabolic. After all, this is the seat of energy and metabolism is how we make/use energy.
So…
- Insulin
- Glucose
- Cholesterol
- Fat
- A1C
Don't get us started!!
PQQ activates AMPK, a key metabolic switch that drives the longevity benefits of metformin, berberine, fasting, etc.
It tightens up the entire metabolic ship!
A fascinating study looked at mice fed a "western diet" and supplemented with PQQ. The effects were long-lived!
PQQ exposure during pregnancy altered hepatic lipid profiles of WD-exposed offspring, upregulating peroxisome proliferator-activated receptor (PPAR) α signaling and mitochondrial fatty acid oxidation to markedly attenuate triglyceride accumulation beginning in utero.
https://pubmed.ncbi.nlm.nih.gov/35682720/
Essentially, the offspring saw better liver processing of fats and sugars (triglycerides) from their mother's PQQ!
A net effect was the protection of gut and liver function:
Surprisingly, the abundance of very long-chain ceramides, important in promoting gut barrier and hepatic function, was significantly elevated in PQQ-treated offspring.
Keep in mind, the liver governs our metabolism to a great extent (fat and sugar processing).
And cholesterol?
In the stratification analysis of the high LDL-chol subgroup (baseline LDL-chol level ≥140 mg/dL), the mean LDL-chol levels decreased significantly from the baseline values in the PQQ group compared to the placebo group.
https://pubmed.ncbi.nlm.nih.gov/26226960/
Animal studies are starting to look at diabetes directly:
STZ-treated animals developed oxidative stress as indicated by a significant increase in tissue lipid peroxidation (LPO) and lipid hydroperoxide, serum glucose, total cholesterol, triglyceride and urea, with a parallel decrease in the levels of serum insulin and tissue antioxidants. When diabetic animals received different doses of PQQ, these adverse effects were ameliorated.
https://pubmed.ncbi.nlm.nih.gov/26343954/
A study looked at fat creating specifically:
Hence, dietary PQQ could prevent obesity by reducing body fat accumulation via suppressing lipogenesis and promoting mitochondrial biogenesis.
https://pubs.acs.org/cms/10.1021/acsfoodscitech.1c00301/asset/images/large/fs1c00301_0007.jpeg
Let's turn to the liver.
Liver disease
How about the most common source of liver dysfunction…alcohol induced cirrhosis.
Our results shows that PQQ can significantly ameliorate acute alcoholic liver injury by decreasing the hepatic marker enzymes, including serum alanine transaminase (ALT) and aspartate transaminase (AST), and increasing the levels of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the liver.
https://www.sciencedirect.com/science/article/abs/pii/S1359511319312930
Goodness…that's a who's who of bad markers (go down) and good markers (go up).
The glutathione (our primary detox pathway) increase is the big one. See our review on glutathione.
Big shocker…triglycerides and malondialdehyde (a toxic metabolite) both went down.
What about the immune system?
Auto-immune
Let's look at a classic example..psoriasis (see our big review here):
Mice treated with PQQ demonstrated marked attenuation of arthritic symptoms based on histopathology and clinical arthritis scores.
https://pubmed.ncbi.nlm.nih.gov/26319019/
Wait…what?
What's fascinating is that PQQ's effect was in modulating key immune inflammatory responders.
What about MS, a disease where the immune system attacks the myelin coating around nerves?
They're literally looking at PQQ to drive myelin growth for repair:
Pyrroloquinoline quinone (PQQ) is an antioxidant that also stimulates nerve growth factor (NGF) synthesis and secretion. In an earlier pilot study in our laboratory, Schwann cell growth was accelerated, and NGF mRNA expression and NGF secretion were promoted
https://pubmed.ncbi.nlm.nih.gov/15915445/
Schwann cells are where myelin is made.
We look forward to more but both immune rebalancing and repair look promising.
On to strokes.
Strokes
Cut to the chase (since we looked at this with TBI above):
PQQ is protective in cases and models of brain aging and neurodegeneration, including Parkinson’s disease, stroke, and traumatic brain injury.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533503/
A big part of the damage that occurs from a stroke is the loss of actual brain mass.
Rats without PQQ supplementation had infarctions across −95 percent of cortices compared to −70 percent in rats pretreated with PQQ.
Let's take a flyer.
Fertility??
The gonads are actually subject to mitochondrial stress due to energy needs and high turnover.
Animal studies are getting interesting.
Dietary supplementation with pyrroloquinoline quinone disodium (PQQ.Na2) improves oxidative status and semen quality in aging layer breeder roosters
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942821/
And the ovary?
These results revealed that ROS-associated damage in FSH-stimulated granulosa cells adversely affects their physiology and follicular health during the follicular development process. Treatment with PQQ is a beneficial tool to increase both the number of ovulated oocytes and pups per delivery.
https://www.sciencedirect.com/science/article/abs/pii/S0891584920321079
Okay…we had to just pick a few. Let's turn to cancer.
PQQ and cancer
Our litmus test for the superior hack is something that selectively hurts cancerous cells while supporting healthy cells.
Few and far between (which is why we're huge fans of CBD isolate and lactoferrin).
So…PQQ.
Music to our ears:
PQQ induced tumor cells apoptosis was significantly alleviated by pan-caspase inhibitor Z-VAD-FMK. The present work highlights the potential capability of PQQ as an anti-tumor agent with low toxicity towards normal cells through activating mitochondrial-dependent apoptosis pathways, and warrants its development for cancer therapy.
https://www.jcancer.org/v05p0609
This is really tricky since the immune system is tasked with detecting and killing cancerous or virally-infected cells.
In fact, mitochondria are at the heart of this process since oxidative stress (controlled by mitochondria) is the preferred weapon.
Chemo and radiation are just massive doses of oxidative stress.
In fact, a study looked at using PQQ to offset the damage of chemo to ovaries:
Results showed that PQQ treatment increased the ovarian weight and size, partially normalized the disrupted estrous cycle period and prevented the loss of follicles of mice treated with AAs. More importantly, we found that PQQ treatment significantly increased the pregnancy rate and litter size per delivery of mice treated with AAs.
https://www.frontiersin.org/articles/10.3389/fendo.2022.781404/full
AA is short for Alkylating agents, a cancer fighting tool that causes huge damage to the ovaries.
Check out our big review on CBD and turkey tail for cancer or our top tools for cancer success.
Finally, if it's good for health foundationally, it should be good for aging.
PQQ and longevity
Mitochondrial function is now one of the pillars of longevity research. In fact, they may be the first shoe to drop (bad DNA repair mechanism).
With advanced age, mitochondrial DNA volume, integrity and functionality decrease due to accumulation of mutations and oxidative damage induced by reactive oxygen species (ROS).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003832/
So…PQQ should have some effect, right?
First, PQQ is all over the popular longevity pathways:
- AMPK - nutrient sensor (more on AMPK); metformin, etc
- mTOR - protein sensor; rapamycin
- SIRT - cellular shock protein; resveratrol, NAD, etc
- Iron balancing - lactoferrin, blood donation/dilution
Longevity studies always start with the worms:
In a roundworm model used to study longevity, PQQ was found to increase lifespan by an average of 30%.
https://www.lifeextension.com/magazine/2021/ss/pqq-aging-cells
Fantastic review of "longevity" vitamins here:
https://www.pnas.org/doi/pdf/10.1073/pnas.1809045115
A study looked at age-related deterioration which is usually slowed by AMPK activation and found that one of the key switches that PQQ triggers…is required!
AMPK-mediated neuroprotection appears to require PGC-1α.
https://www.sciencedirect.com/science/article/pii/S019745801730091X?via%3Dihub
This is exciting. PPGC-1α is directly driven by PQQ!
PQQ exposure stimulated phosphorylation of CREB at serine 133, activated the promoter of PGC-1α, and increased PGC-1α mRNA and protein expression.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804159/
Yes, please.
Okay…let's get practical.
Practical questions on PQQ
The general reading is around 20mg of PQQ for a standard dose.
BioPQQ is processed differently (better) via fermentation as opposed to a pretty harsh chemical process and that's the best approach.
We use this one here:
Here's the thing, we can't find contraindications or issues with PQQ supplementation at these levels which is pretty odd. We can't even find interactions with medications (check with your doctor) which is also atypical since a key pathway in the liver processes most meds.
Research points to PQQ as an adjuvant option with cancer treatment. In fact, research is on protecting healthy tissues (i.e., nerve damage and ovarian function, etc.) with PQQ from treatment.
Work with your doctor of course…with all supplements.
PQQ, along with lactoferrin and CBD isolate make up our Triple Threat for health and longevity.
Very exciting times!