What the PQQ brain-supplement trial found

Disclosure up front: I run a functional-mushroom supplement company, so "supplements for your brain" is a category I have a commercial stake in. I have no connection to this trial, its authors or the product. The full disclosure is at the bottom.

The trial

Barbara Kozma and colleagues at the University of Debrecen in Hungary randomized 70 healthy postmenopausal women to one capsule a day of either a commercial supplement called Cortexium or a maltodextrin placebo, for six weeks. The paper went online on 3 November 2026 as an accepted early version, which the journal says may still be edited before the final Version of Record. The trial was registered in advance as NCT06748989.

The capsule is not just PQQ. Per the paper's ingredient table, each one holds 20 mg PQQ, 100 mg GABA, 100 mg caffeine, a full set of B vitamins at 100% of the reference intake, 80 mg vitamin C, 14 mg iron, 60 mg magnesium and 5 mg zinc. For scale, FDA lists a 12-ounce cup of regular brewed coffee at 113 to 247 mg of caffeine, so the capsule carries somewhat less than one cup.

Cognition was measured with CNS Vital Signs, a computerized test battery, at the start and again shortly after the six weeks ended. The pre-specified primary outcome was its Neurocognition Index, a global composite score. That matches what the registry lists as the primary outcome, which is a point in the trial's favor: the headline result is the one they said in advance they'd lead with.

What it found

Sixty-three women were analyzed, 30 on the supplement and 33 on placebo. After adjusting for baseline scores, the supplement group finished 5.89 points higher on the Neurocognition Index, with a 95% confidence interval of 1.27 to 10.52 and p = 0.013. The authors had set 5 points as the minimal clinically important difference when they planned the study, so the point estimate clears their own bar, though the lower end of the interval does not.

Then there are the eleven secondary domain scores. Three came out significantly in the supplement's favor: Memory (+7.86), Visual Memory (+7.97) and Cognitive Flexibility (+7.57). Executive Functioning was close (p = 0.053). Six others, including Verbal Memory, Reaction Time and Processing Speed, showed no significant difference. And one, Complex Attention, came out significantly worse on the supplement: on that test lower scores are better, and the supplement group scored 10.32 points higher (p = 0.019). The authors report this plainly and call its meaning uncertain.

No serious adverse events occurred. The paper says minor events were infrequent and similar between groups, without giving counts in the text I read.

Five things to know before you believe the headline

1. It tested a blend, so it can't credit PQQ. The authors say this themselves: with PQQ, GABA, caffeine, vitamins and minerals in one capsule, the trial cannot tell which ingredient, if any, did the work. A marketing line that says "PQQ improved memory in a clinical trial" would be overreaching on this study.

2. The caffeine question is narrower than it looks. The obvious suspicion with a caffeinated capsule is a simple stimulant bump at test time. The design rules that out: participants did not take a capsule on the day of the final test. That's good design. But two caffeine questions remain open in what I read. The paper doesn't report participants' usual coffee or tea intake, which affects how much 100 mg extra means. And it doesn't report checking whether participants could guess their group. A daily dose of caffeine against a maltodextrin placebo is the kind of thing some people can feel, which matters for a "double-blind" claim. (Older caffeine research, which I've only read in abstract, also finds that habitual users build tolerance to caffeine's mental effects, which cuts against the idea that a daily dose sharpens thinking over weeks.)

3. Eleven sub-scores, no correction. The paper applied no multiplicity adjustment to the secondary outcomes and labels them exploratory. That is the honest label. Run eleven tests and a couple of p-values under 0.05 can appear by chance alone, in either direction. The pattern here (three favorable, one unfavorable, seven not significant) is what I'd call suggestive, not established. Only the primary result carries real weight.

4. Small, short and a bit lopsided in who was analyzed. Seventy women enrolled and 63 were analyzed. Five of the seven excluded were from the supplement group, for incomplete data or not returning, and the analysis used only women with both test sessions. The study was planned around a one-sided test and then reported two-sided p-values, which the authors flag as lowering the effective power. Six weeks, one center, one test battery. The tables report completion scores and the adjusted difference; I didn't find each group's starting cognition scores in the article text, so you can't see how much each arm actually changed.

5. The sponsor line doesn't match the registry. The paper's funding statement reads "Investigator initiated. No outside funding was used," and the authors declare no competing interests. The paper also says the manufacturer, Fempharma, supplied the capsules and placebo and packaged and labeled them according to the randomization list, but had no role in enrollment, testing, analysis, interpretation or submission. The ClinicalTrials.gov record, however, lists FEMPHARMA Kft. as the lead sponsor and the responsible party, classed as industry. Those can be reconciled (a company can register and supply a study the investigators run), but a reader should know the product's maker is named as the study's sponsor on the official registry.

How it fits the PQQ literature

I ran a literature search to see whether this trial stands alone. It doesn't, but the earlier evidence is thin in a similar way. Two Japanese trials of PQQ by itself, about 20 mg a day for 12 weeks, reported improvements on a comparable computerized battery: one in 64 healthy adults aged 40 to 80, using a branded PQQ ingredient, and one in adults aged 20 to 65 that found different domains improved in younger versus older participants. I read only the abstracts of both. They are small and short, which is roughly where this new trial sits too. The field does not yet have a large, long, independently funded PQQ trial with a hard real-world outcome.

How I'd read it

A pre-registered primary outcome that moved by about the amount the authors called meaningful is a genuine, modest result. It is not nothing. But it's one six-week trial of a fifteen-ingredient capsule, with secondary scores that point both ways, in a group of healthy women who weren't selected for having cognitive complaints. The responsible summary is: this blend beat placebo on a computerized global score in one small study, and nobody knows yet which part of it mattered or whether the effect lasts.

If you're evaluating a PQQ product, the question to ask is whether the claim on the label is about the ingredient or about a tested formula, and whether the trial behind it was this kind of study or a bigger one.

What would change my read: the final Version of Record with group-level baseline scores, a replication by an independent group, a trial that separates PQQ from the caffeine and GABA, or any trial running longer than three months. If one lands, I'll update this post in place.

Not medical advice. This is educational analysis, not a recommendation — a study is not a prescription. Talk to a qualified clinician before acting on anything you read here. Full disclaimer →

Disclosure, plainly: I founded and run Shroombiosis (a company I run), which formulates and sells functional-mushroom supplements, so I have a commercial stake in how people think about supplements and the brain. I have no relationship with this trial, its authors, Fempharma or the product. Nothing here is sponsored and no link earns a commission; here's the full policy. A recommendation with no stake at all: for performance nutrition, Die Tryin Co. is a fellow combat-veteran-owned brand I'm glad to point people to. I don't own it and earn nothing from the link.