PQQ: Boost The Energy In Your Cells To Do Everything Better

By: Dave Asprey

Upgrading the energy in your cells through PQQ supplements is one of the most effective ways to improve your performance across all realms of life.

Your cellular energy comes from mitochondria, which are the powerhouses of the cell. Mitochrondria are the tiny organelles working to produce cellular ATP, or adenosine triphosphate, the energy currency of your cells.

Mitochondrial density is greatest in the areas of your body requiring the most energy, like your brain. Also, these structures are not in the least bit static; they constantly change. Mitochondrial dynamics include fission and fusion, as well as destruction (mitophagy) and renewal, known as mitochondrial biogenesis.[1]

This is awesome news, because it means you can make your existing mitochondria work better and you can even literally grow more “power plants” in your cells.

Why Would You Want To Supercharge Your Mitochondria?

My own mitochondrial function has been a focus of biohacking for years…and a huge number of the things I do have a direct impact on how mitochondria work. Things like ketosis, Brain Octane, high intensity exercise, Bulletproof intermittent fasting, and avoiding toxins all help mitochondria.

Scientists have been studying mitochondria for a long time, including some of the molecular mechanisms behind mitochondrial biogenesis.

Your mitochondria are the home of the Krebs cycle (aka citric acid cycle,) which explains how our bodies get energy from glucose (from eating carbs) or ketones (from burning fat). It’s how humans make energy from different sources of fuel.

If you find a way to improve your mitochondrial function, you’ll make energy more efficiently. One of the most exciting new ways of increasing mitochondrial function is the compound PQQ or pyrroloquinoline quinone.

If you can successfully get PQQ past your digestive system, it has a measurable impact on mitochondrial function and it can cause mitochondrial biogenesis. In other words you can get better cellular energy now, and over time a “bigger engine” in your cells.

Without getting too geeky, PQQ can influence the epigenetics of a cell, primarily through the signaling molecules PGC-1, CREB, and DJ-1.[2] PQQ also functions as an antioxidant, resulting in decreased inflammation and oxidative stress.[3] Or you can read up on how epigenetics works first.

The Benefits of PQQ

There is a lot of research supporting PQQ’s ability to kick our mitochondria into high gear. Specifically, research shows it can:

  • Increase mitochondrial density to give you more energy[4]
  • Reduce inflammation[5]
  • Boost metabolism[6]
  • Combat oxidative stress[7]
  • Improve fertility[8]
  • Improve learning and memory ability[9]

One study showed that PQQ improves the reproductive performance of mice, as well as growth of newborn mice.[10] Mice in the PQQ-supplemented group averaged 8 pups/litter, compared to 4-5 pups/litter in the PQQ-deficient group. This suggests that the mitochondrial health of parents has a significant impact on their offspring’s potential to thrive. (You already may know something about epigenetics if you’ve read this blog much!)

Another study showed that deprivation of PQQ in rats and mice led to a decrease in mitochondrial density, [11] which means that a deficiency in PQQ may be responsible for low energy levels.

PQQ also helps jumpstart your metabolism: total energy expenditure and ?-oxidation potential (which is a measure of fatty acid metabolism) are both higher in rats given PQQ.[12] Remarkably, PQQ also improves learning ability in rats, and these memory improvements are maintained even when the rats are exposed to 48 hours of hyperoxia (a form of oxidative stress).[13] So, PQQ may help you get fitter and smarter, simultaneously.

While most studies concerning PQQ have been conducted on animals, data from humans also shows parallel promise. One such study gave participants either a single dose (0.2mg PQQ/kg or around 10mg for a 100 lb person) or a daily dose (0.3mg PQQ/kg) of supplemental PQQ, and reassessed them after 76 hours.[14] Those who received recurring supplementation of PQQ showed significantly decreased levels of C-reactive protein, interleukin 6, and urinary methylated amines, as well as changes in urinary metabolites that are indicative of enhanced mitochondrial functioning. Regulation of myokines such as interleukin 6 is incredibly complex, and a key to health, as Dr. Doug McGuff explains in this Bulletproof Radio episode.

So it’s kind of exciting to think about taking a supplement with systemic effects – PQQ works to regulate a slew of inflammatory molecules to our advantage. That’s why I started taking 30-40mg of the common form of PQQ every day 4 years ago. However, unlike other mitochondrial energizers, I never felt any effect. It’s possible it was doing something, but nothing detectible. PQQ is an expensive supplement, and I’m now convinced I was wasting my money and time on it.

Why the Form of PQQ (Active) Matters

The likely reason I didn’t feel any energy from large doses of PQQ over extended time is that PQQ is sold as the “stabilized” disodium salt form, because it’s more convenient for the manufacturer. Unfortunately, in humans, disodium salts precipitate when they are exposed to even small amounts of stomach acid. That means all that expensive PQQ I took was turning into little rocks in my stomach, and not helping my mitochondria the way I wanted it to.

So what’s a biohacker to do?

You know what they say…if you want it done right…

I set out to synthesize PQQ directly, targeting an acid form of PQQ that would be at home in stomach acid, and bypass the problem with standard PQQ supplements. That is how ActivePQQ™ was born.

ActivePQQ™ also improves absorption by creating a pre-colloidal and colloidal suspension with particle sizes so small they remain suspended in water.

The brand-new whole body energizer and nootropic Unfair Advantage™ uses colloids – permanently suspended nanoparticles – of ActivePQQ and CoQ10 to create a supplement that activates mitochondria so powerfully that you can feel it work very quickly.

ActivePQQ and CoQ10 work well together as colloids because the CoQ10 helps the PQQ absorb especially well – that’s why there’s a 2:! ratio of CoQ10 to ActivePQQ™. (I recommend you take larger doses of CoQ10 separately too!)

Unfair Advantage™ is the only product on the market today that delivers the active form that bypasses your stomach acid, ActivePQQ™. Suspended in a colloid so that it’s easily absorbed and fast acting, Unfair Advantage™ will turn the lights on for your mitochondria.

It’s the most important supplement I’ve ever created, and I’m really excited about it.

You owe it to yourself to take care of your mitochondria, because mitochondrial dysfunction is behind nearly every degeneration that happens as you age. Whether or not you use Unfair Advantage, make sure you do something to grow your mitochondria and keep them healthy, like heavy resistance training, Bulletproof Intermittent fasting, cold thermogenesis, Brain Octane Oil, or even bright red LED light therapy.

Strong mitochondria make for strong people!


How It Works: The Science Behind PQQ for Geeks

PQQ works through various mechanisms of action to alter the epigenome for increased mitochondrial functioning. Here’s how these pathways work.

As seen in Figure 1 the signaling molecules occur inside the cell, and they are activated by PQQ, which does not have to cross the cell membrane in order to exert an effect. Rather, PQQ binds to receptors on the surface of the membrane, triggering 2nd messengers that induce intracellular signaling cascades. These molecules are capable of directly interacting with the cell’s DNA, which change the parts of the genome that are expressed – this is what is known as epigenetics.

(See Figure 1)

figure01PGC-1? is one of the messengers that is effected by PQQ. The genes which it regulates are involved in energy metabolism, determination of skeletal muscle fiber type, and thermogenesis of brown adipose tissue.[15], [16] For these reasons, a lack of PGC-1? has been implicated in obesity and type-II diabetes.[17], [18], [19] Additionally, PGC-1? is required for the induction of many detoxifying enzymes, as shown in vitro, and PGC-1?knockout mice are much more sensitive to neurodegeneration by oxidative stress.[20]

PGC-1? is well known to stimulate mitochondrial biogenesis,[21] but how does this pathway work? Referring again to Figure 2, PGC-1? is activated by a factor upstream of it, cAMP response element-binding protein (CREB). When a cell is exposed to PQQ, it initiates activation of AMPK, or various other protein kinases, which in turn activate CREB through phosphorylation at serine 133.[22] CREB works both to initiate PGC-1? signaling, and act directly on the genome, at sequences termed cAMP response elements.[23]

PQQ also increases the activity of DJ-1.[24] This signaling molecule is involved in protecting neurons against oxidative stress,[25] and mutations in its gene have been cited in Parkinson’s disease.[26], [27] Thus the role of DJ-1 is likely to prevent neuronal cell death, and could account for the protective effect of PQQ against neurotoxins.[28]

figure2(See Figure 2)

Mitochondrial deficiencies have been cited in aging theories for a long time, and are starting to be implicated in neurodegenerative disorders as well.[29] In Parkinson’s disease patients, there is decreased expression of the target genes for PGC-1?.[30] Levels of PGC-1? also correlate negatively with the extent of dementia in those with Alzheimer disease (AD). [31] Importantly, in vitro overexpression of PGC-1? leads to complete rescue of the cell model for AD.[32] This makes sense, considering that PGC-1? modulates mitochondrial functioning and cellular detoxification, as seen in Figure 2.

Lastly, PGC-1? improves motor functioning and survival in the mouse model for ALS.[33]









[7] Ibid., 3


[9] Ibid., 3

[10] Ibid., 8

[11] Ibid., 4

[12] Ibid., 7

[13] Ibid., 3

[14] Ibid., 6









[23] Ibid., 2









[32] Ibid., 31