PQQ: The Supplement That Builds New Mitochondria for Energy and the Brain

Almost every supplement marketed for healthy aging promises one thing: to protect your existing mitochondria from oxidative damage. PQQ, or its full name pyrroloquinoline quinone, offers something fundamentally different. Instead of just protecting, research shows it stimulates the cell to produce entirely new mitochondria, a process called mitochondrial biogenesis.

This is not a minor issue. A decline in the number and quality of mitochondria is one of the 12 hallmarks of aging. As we age, the energy factories in our cells diminish and lose efficiency, manifesting as fatigue, cognitive decline, and metabolic slowdown. A molecule capable of reigniting this production line has attracted serious attention, both from longevity researchers and the supplement industry. But how much of this is based on real human science, and how much on marketing? Let's separate the two.

What is PQQ?

PQQ is a small, redox-active quinone compound, first discovered as a coenzyme in bacteria. Here is what is important to know about it:

• It is found in food. Small concentrations appear in natto (fermented soybeans), spinach, green peppers, kiwi, and green tea. Human milk contains it, suggesting a biological role.
• It is an exceptionally stable antioxidant. A single molecule of PQQ can undergo thousands more redox cycles than vitamin C, making it highly effective at neutralizing free radicals.
• It is not an official vitamin. Although it has been discussed as a 'new vitamin', it does not yet have an official definition as an essential nutrient in humans.
• The common dosage in supplements is 10-20 mg per day, a common form is the disodium salt (BioPQQ).

The feature that sets PQQ apart from other antioxidants is not just quenching radicals, but its rare ability to communicate with the genetic control mechanism of mitochondrial production. That is where the truly interesting story begins.

The Connection to Mitochondria: A Mechanism That Ignites an Energy Factory

The mechanism of PQQ is the most well-established part of its research, and also the most impressive. In a landmark study published in the prestigious Journal of Biological Chemistry in 2010, researchers from the University of California showed exactly how it works.

When they exposed mouse liver cells to a concentration of 10 to 30 micromolar PQQ for 24 to 48 hours, they measured a significant increase in all markers of new mitochondria: citrate synthase enzyme activity, cytochrome c oxidase activity, mitochondrial DNA quantity, and cellular oxygen consumption. In simple terms: the cells physically produced more active mitochondria.

How? PQQ activates a central regulatory protein called PGC-1alpha, sometimes referred to as the 'master conductor' of mitochondrial biogenesis. It does this through phosphorylation of a protein called CREB. When the researchers silenced the genes for PGC-1alpha or CREB, PQQ completely stopped producing new mitochondria, direct proof that this is the pathway through which it works. Later studies added two additional pathways leading to the same result: activation of SIRT1, the same longevity enzyme influenced by NAD, and activation of AMPK, the cell's energy sensor.

This is why PQQ is often combined with CoQ10. The two work in a chain: PQQ builds more mitochondria, and CoQ10 is an essential component of the electron transport chain within each mitochondrion. The idea is more factories, each operating efficiently.

Current Evidence in Humans

Here we need to be fair. Most of the impressive mechanism we described has been proven in cells and rodents. Human studies exist, but they are small and short-term. Here are the three most prominent ones.

Study 1: Fatigue, Stress, and Sleep (Nakano, 2012)

A Japanese open-label study followed 17 adult participants who took 20 mg PQQ daily for 8 weeks. Using validated mood questionnaires, the researchers found a statistically significant improvement in all six mood measures: vigor, fatigue, tension-anxiety, depression, anger, and confusion. Additionally, quality of life, appetite, sleep, and pain measures improved. Specific sleep tests showed improvement in ease of falling asleep, sleep continuity, and sleep duration. The downside: only 17 participants and no placebo group.

Study 2: Memory and Brain Function (Tamakoshi, 2023)

A double-blind, placebo-controlled study, the gold standard of clinical research, was published in the journal Food and Function. 70 participants aged 20 to 65 received 20 mg PQQ daily for 12 weeks. The results were age-dependent: in adults aged 41 to 65, improvement was measured in composite memory and verbal memory after 12 weeks. In younger adults aged 20 to 40, improvement in cognitive flexibility and processing speed was measured as early as 8 weeks. This is one of the higher-quality studies supporting cognitive use.

Study 3: Mild Cognitive Impairment (RCT, 2024)

A recent controlled study examined 34 elderly individuals with mild cognitive impairment (average age 71.9) who received a mixture of PQQ or placebo twice daily for 6 weeks. A significant improvement was found in the orientation subscale of the Alzheimer's Disease Assessment Scale. Additionally, brain oxygen saturation increased from 48.4% to 52.8%, a finding directly consistent with the theory that mitochondria are working more efficiently.

What About Energy and Physical Activity?

The application that attracts the most users is the feeling of energy. The mechanistic logic: more active mitochondria should translate to more ATP, the body's energy currency. The Nakano study indeed found an increase in vigor and a decrease in subjective fatigue. However, it is important to be precise: there is currently no strong evidence that PQQ improves measurable athletic performance like strength or endurance in a way that surpasses training. The consistent finding is a subjective feeling of less fatigue and more vigor, not a leap in sports performance. This is an important distinction for those considering it as a tool for the gym versus a tool for daily vitality.

Should You Start Taking PQQ?

This is where our yellow rating comes in. PQQ is not a red rating like NMN or resveratrol, it has a well-established mechanism and several positive human studies. But it is also not a green rating like vitamin D or omega-3. Here are the considerations:

• Study size: The human studies number in the tens of participants, not thousands. There are no large, long-term studies confirming benefit for lifespan or disease prevention.
• Safety: PQQ is considered safe at doses of 10-20 mg. Reported side effects are rare and mild, mainly gastrointestinal discomfort or sleep disturbances at high doses if taken in the evening.
• Cost: A monthly bottle typically costs 80 to 150 NIS, more expensive than basic supplements but much cheaper than NMN.
• Warning: There is insufficient data on safety during pregnancy and breastfeeding, so it should be avoided during these periods. Those taking chronic medications should consult a doctor.

The bottom line: This is a reasonable supplement to try for those seeking support for energy and focus, with realistic expectations. If you are interested, purchasing PQQ on iHerb is available in various forms.

What to Take Away from the Research?

1. If you try PQQ, start with 10-20 mg per day in the morning. Morning intake reduces the risk of sleep disturbance reported by some users at high evening doses.
2. Consider combining with CoQ10. The two supplements work synergistically on mitochondria, and this is the common combination in research and the market.
3. Give it time. In studies, cognitive benefit appeared only after 8 to 12 weeks. Do not expect results within two days.
4. Don't neglect the free stuff. Aerobic exercise, high-intensity interval training, and intermittent fasting activate the same PGC-1alpha pathway naturally and powerfully, at no cost.
5. Find your personal fit through our personal supplement selector, which matches evidence-based supplements to your goals.

The Broader Perspective

PQQ is an excellent example of a supplement that lies in the gray area of longevity science: a beautiful and well-established mechanism in the lab, but human evidence that is still too thin to draw a definitive conclusion. It is not a scam like some supplements, but it is also not a magic solution.

If there is one lesson, it is this: Its most powerful mechanism, activating PGC-1alpha and mitochondrial biogenesis, is activated for free and with greater efficiency by physical exercise. A supplement can give a small boost, but it will never replace the lifestyle that ignites those same mechanisms powerfully. Anyone seeking younger mitochondria should first move, and only then consider the bottle.

References:
Chowanadisai et al., Pyrroloquinoline Quinone Stimulates Mitochondrial Biogenesis through CREB Phosphorylation and Increased PGC-1alpha Expression, Journal of Biological Chemistry, 2010
Nakano et al., Effects of Oral Supplementation with Pyrroloquinoline Quinone on Stress, Fatigue, and Sleep, Functional Foods in Health and Disease, 2012
Tamakoshi et al., Pyrroloquinoline quinone disodium salt improves brain function in both younger and older adults, Food and Function, 2023