Three Recent Supplement Trials — and Who Paid for Them

Abstract

Between 2023 and 2024 three randomised placebo-controlled trials tested single cognitive supplements in healthy adults: alpha-GPC, ashwagandha, and a comparison of guayusa extract with lion's mane. All are recent, all are properly designed, and all report positive findings.

They are also, in whole or in part, funded or advised by companies with an interest in the outcome — which the authors disclose, and which nobody quoting the results tends to mention.

This article reads the three trials on their merits and then reads the funding statements, because both are part of the evidence.

1.Why These Trials Matter

As our companion article on the nootropic reviews sets out, the field's central weakness is that most evidence comes from clinical populations. Trials in healthy adults are rare, which makes recent ones disproportionately influential in marketing.

All three used designs that address that gap: randomised, double-blind, placebo-controlled, in healthy volunteers, with pre-specified cognitive batteries. On design alone they are better than most of what this category cites.

2.Alpha-GPC

Alpha-glycerylphosphorylcholine is a choline compound, related in rationale to the citicoline literature discussed elsewhere in this library. The 2024 trial examined acute supplementation in healthy men, run at a contract research organisation using a randomised, double-blind, placebo-controlled crossover design.

Its control of confounds is worth noting: participants replicated food and fluid intake for 24 hours before each visit, fasted overnight for at least eight hours, avoided exercise for 48 hours, and avoided caffeine, alcohol and choline-containing foods for 24 hours.

The prior literature it reviews is mixed in an instructive way. An earlier crossover study found serial subtraction scores 18.1 per cent faster than caffeine and 10.5 per cent faster than placebo at a 200 mg dose — but reported no statistically significant change. Another study combining 500 mg alpha-GPC with uridine monophosphate and DHA found no effect on vertical jump or bench press.

The funding disclosure is explicit and, to the author's credit, accompanied by a management plan: the author serves as a paid scientific advisor to the study sponsor, NNB Nutrition, and under a plan agreed with his university was not involved in consenting participants, collecting data, or analysing it before unblinding.

That is close to best practice for industry-funded work. It does not remove the conflict; it constrains the channels through which it could operate.

3.Guayusa and Lion's Mane

The 2023 trial is the most instructive of the three. Forty healthy adults aged 18 to 50, who habitually consumed no more than 240 mg of caffeine daily, completed a double-blind, randomised, three-arm, placebo-controlled crossover comparing 650 mg of a standardised guayusa extract against 1 g of lion's mane fruiting bodies against maltodextrin placebo.

Significant interactions were reported for Go reaction time and for N-back score and accuracy. Read alone, that supports both botanicals as acute cognitive aids.

Now the detail that changes the interpretation. The guayusa extract was standardised to 20 per cent caffeine — meaning the 650 mg dose delivered 130 mg of caffeine, roughly a strong cup of coffee, to participants selected for low habitual caffeine intake.

Comparing a caffeine-containing botanical against maltodextrin does not isolate the botanical. The authors themselves cite an earlier study finding no significant difference between this extract, an equal dose of caffeine alone, and placebo on several cognitive tests — which is the comparison that would settle it.

The trial was funded in part by Applied Food Sciences, the company that produces the guayusa extract.

On lion's mane the authors are usefully candid: most studies have examined people with cognitive impairment, only a few have looked at healthy adults, and none had previously investigated acute single-dose effects.

4.Ashwagandha

The 2024 ashwagandha trial examined both acute and repeated supplementation on markers of cognitive function and mood in healthy participants, and reported improvements on both.

Ashwagandha has a larger human literature than most botanicals in this space, concentrated on stress and sleep outcomes. The recurring methodological issue across it is that extracts differ between manufacturers, so results attach to a specific standardised preparation rather than to the plant — the same problem we describe for rhodiola in our formulation pages.

5.What to Do With Industry-Funded Trials

The unhelpful responses are to dismiss them or to ignore the funding. Neither is right.

Most nutrition research is industry-funded because public funders rarely pay to test supplements. Refusing to read such work would mean refusing to read the field. The disclosures above are also genuine disclosures — declared, detailed, and in one case accompanied by a formal management plan.

What funding should change is the weight placed on a single trial. An industry-funded positive result is a reason to want independent replication, not a reason to conclude. And it makes the design details matter more, not less — which is how the caffeine content of the guayusa arm becomes the most important number in that paper.

Our practical rule when reading any trial in this category: find the funding statement before the results, then read the intervention description carefully enough to know what the placebo was actually being compared against.

Editorial Comment

MindHeaven® does not currently use alpha-GPC, ashwagandha, guayusa or lion's mane, and makes no claims about them. None of these trials concerns our formulations.

We hold ourselves to what we have written here. If we commission research on our own compounds, the funding relationship will be disclosed as plainly as these authors disclosed theirs, and a single company-funded positive result will not be presented as settled — including when the company is us.