Bacteria’s Spark, Your Cells’ Fire: The Curious Journey of PQQ from Lab Bench to Mitochondria

The cofactor that wouldn't stay in its lane

In the late 1970s, enzymologists isolated a mysterious helper molecule from bacteria that oxidize alcohols. They called it pyrroloquinoline quinone—PQQ for short—and realized it was a built-in power adaptor for certain bacterial enzymes.^[1] PQQ soon escaped the petri dish and showed up in another place: the chemistry of glucose test strips. Those strips use PQQ-dependent enzymes to pull electrons from sugars and turn them into a readable electric signal—useful, but also a cautionary tale, because that bacterial enzyme can misread other sugars and dangerously inflate glucose readings in some medical settings.^[2]

That dual identity—a precise biochemical tool in one world, a blunt instrument in another—set the stage for PQQ's next role: a possible ally for human cellular energy.

The vitamin debate that sharpened the science

Early on, a bold claim appeared: maybe PQQ was a new human vitamin. The idea electrified nutrition science, then faltered. Replication efforts argued the key enzyme target wasn't actually PQQ-dependent, and critics concluded the "new vitamin" announcement was premature.^[9] Even one of PQQ's discoverers reflected that the "hopes that PQQ could be a new vitamin have diminished strongly," a line that captured a field learning to separate excitement from evidence.^[1]

Yet the story didn't end there. Years later, biochemist Bruce Ames proposed a broader category—"longevity vitamins"—nutrients that aren't required to keep you alive today but support proteins that preserve health over decades. He placed PQQ on that putative list, writing that nutrients for these proteins form "a class of vitamins ... named 'longevity vitamins.'"^[10]

Following the signals into the cell

Here's where the detective work pays off. In cultured mammalian cells, PQQ acts like a foreman who flips on the lights in the cell's power-plant factory. It activates CREB, a switch on the control panel, and boosts PGC-1α, the master coordinator that tells the nucleus to build and maintain more mitochondria. Downstream, the genes that specify components and caretakers of mitochondria spring to life.^[3][14] In another line of evidence, researchers observed that PQQ increases cellular NAD+ and nudges SIRT1, a maintenance enzyme that "de-gums" PGC-1α so it can work better—another way to encourage new, efficient mitochondria.^[12]

If that sounds abstract, picture this: your cells run an aging fleet of engines. PQQ doesn't pour gas into them; it hands the shop a better maintenance checklist and a budget to assemble more engines.

From bench to people: what changes first?

When PQQ moved from dishes to volunteers, the first signals showed up not as superpowers but as quieter inflammation and metabolic fingerprints of better mitochondrial work. In a crossover study, healthy adults taking PQQ for just a few days showed drops in C-reactive protein and IL-6—blood markers of inflammatory tone—and shifts in urine metabolites consistent with improved oxidative metabolism.^[4] That's not a cure-all; it's a nudge in systems we care about.

Sleep and stress drew attention next. In an 8-week open-label study, adults taking 20 mg/day reported better sleep initiation and duration, improved morning alertness, and lower scores for tension and fatigue—changes that tracked with a calmer cortisol awakening response.^[5] Open-label means placebo effects can't be ruled out, but the pattern suggested a direction for controlled trials.

Cognition: the first randomized signals

Those trials arrived. In a 12-week randomized, double-blind study of healthy middle-aged and older adults (~21.5 mg/day), the PQQ group improved on composite and verbal memory, reaction time, complex attention, and executive function—measured with standardized cognitive batteries—without safety issues.^[6] A second trial spanning ages 20–65 found that younger adults saw gains in processing and execution speed by week 8, while older adults showed memory improvements by week 12 on validated cognitive tests.^[7]

Under the hood, small studies have also observed increased prefrontal oxygenation after 12 weeks of PQQ at 20 mg/day, hinting that better fuel management might translate to sharper performance on attention tasks.^[11]

Taken together, human evidence suggests this arc: early biomarker shifts (days), subjective sleep/stress improvements (weeks), and measurable cognitive benefits (8–12 weeks). The magnitude isn't pharmaceutical; the direction is promising—and consistent with the mitochondrial maintenance story.

What PQQ is—and isn't—doing

• It's not a stimulant. Think of PQQ as a project manager for cellular upkeep, not a quick jolt.^[3]
• It doesn't flood you with antioxidants; rather, it flips genetic programs that help cells build, protect, and replace their energy hardware—more power plants, better wiring.^[3][12][14]
• It's not proven to transform athletic performance. In a 6-week study pairing 20 mg/day with endurance training, untrained men did not outperform placebo on aerobic endpoints despite the theoretical overlap with exercise-induced mitochondrial gains.^[12]

How people tend to use it (and what regulators say)

In trials, daily intakes around 20–21.5 mg of PQQ disodium salt have been common and well tolerated over 8–12 weeks.^[6][7] Europe's food-safety authority has reviewed PQQ disodium as a novel food and accepted up to 20 mg/day for healthy adults, noting its presence in foods like natto, green tea, and tofu—though at nanogram levels that don't approach supplement doses.^[8]

A practical pattern many adopt:

• Dose: 10–20 mg/day, often with the first meal to minimize any mild stomach sensitivity.
• Timeline: Give it 8–12 weeks for cognition-related outcomes; some people notice sleep/stress changes earlier, but controlled evidence there is less robust.^[5][6][7]
• Pairings: Some studies have combined PQQ with cognitive tasks or attention testing that track oxygenation changes in the prefrontal cortex, but clear synergy claims with other supplements remain preliminary.^[11]

Culture, craft, and a small paradox

It's fitting that one of the richest food sources of PQQ is natto, a traditional Japanese fermented soybean dish, where bacteria quietly manufacture PQQ as part of their own metabolism.^[8] The paradox is elegant: the molecules that help microbes harvest energy from their world may help our cells maintain the machinery that harvests energy from ours.

Where the trail points next

Researchers are now probing how PQQ's "maintenance crew" might matter in aging brains and metabolic health. A small 2024 trial combining dissolved hydrogen with PQQ in older adults with mild cognitive impairment hinted at increased brain-derived neurotrophic factor, better orientation scores, and higher cerebral oxygenation over six weeks—intriguing, but early and blended with another intervention.^[15] A 2024 review urged larger, longer studies in obesity and inflammation, given preliminary human data on CRP and IL-6.^[16] Even outside cognition and metabolism, animal work continues to test PQQ's influence on inflammation and tissue resilience, such as ovarian reserve models—interesting biology, still far from clinic.^[17]

The meta-mystery remains: not whether PQQ is today's missing vitamin, but whether it's tomorrow's reliable tool for keeping our cellular engines tuned. As the evidence matures, measured optimism is warranted.

"The hopes that PQQ could be a new vitamin have diminished strongly," wrote one pioneer, assessing the early exuberance with the benefit of hindsight.^[1]

And yet, as Bruce Ames argued decades later, nutrients that support long-term maintenance "constitute a class of vitamins ... named 'longevity vitamins.'"^[10]

Between those two sentences sits the present: a bacterial cofactor stepping carefully into human health, one controlled study at a time.