We've evaluated two supplements with real cognitive evidence behind them: creatine and omega-3. Creatine's evidence is why we carried it for as long as we did, though it's since been discontinued from the Proco range; omega-3 remains part of the range today. In the interest of the same honesty we apply to every ingredient we evaluate, it's worth asking how that evidence stacks up against the single highest-evidence intervention for brain health: exercise. This isn't a marketing question for us — it's the question we'd want answered before spending money on a bottle instead of a pair of running shoes.
It's also a question most supplement companies never ask, because the honest answer complicates the pitch. We'd rather complicate the pitch than overstate what a capsule can do. So this article walks through what the exercise literature actually shows, how it was measured, how it stacks up next to the creatine and omega-3 evidence we rely on for our own products, and what happens in the one trial that tested combining exercise with a supplement directly.
What exercise actually does, measured properly
A 2026 systematic review and three-level meta-analysis pooled 50 randomized controlled trials in 4,826 cognitively healthy older adults, comparing aerobic exercise, resistance training and multimodal programs against controls.1 The overall effect on executive function was real but modest (g=0.155), with working memory showing the strongest signal (g=0.208). The best-performing protocols — moderate intensity, at least 3 sessions a week, 60 minutes or less, run for up to 26 weeks — reached a considerably larger effect (g=0.254). Both aerobic and resistance training worked; more wasn't automatically better, and moderate intensity outperformed going harder.
That last detail matters more than it might seem. A lot of fitness advice assumes harder and longer is always better for the brain as well as the body, but this dataset says otherwise: the sub-group of trials using moderate-intensity, time-capped protocols consistently outperformed the ones pushing higher intensity or longer sessions. For someone deciding how to spend a limited number of weekly hours, that's a useful, specific finding — and a very different kind of claim than "take more of this ingredient," which is usually where supplement dosing advice ends up.
The clearest evidence: exercise changes brain structure, not just test scores
Meta-analytic effect sizes are useful, but one older trial makes the mechanism concrete. In a year-long randomized controlled trial, 120 sedentary older adults were assigned to either a walking program (40 minutes, three days a week) or a stretching-and-toning control group.2 The walking group's hippocampus — the brain region most associated with memory and most vulnerable to age-related shrinkage — grew by 2.12% on the left side and 1.97% on the right over the year. The stretching group's hippocampus shrank by roughly 1.4% over the same period, which is the typical rate of age-related decline. The volume gains tracked with increases in serum brain-derived neurotrophic factor (BDNF), a protein involved in forming new neural connections.
That's a genuinely different kind of evidence than anything a supplement trial has produced for cognition: a structural brain change, in a controlled comparison, tied to a plausible biological mechanism. It's also why exercise anchors every serious clinical recommendation for healthy brain aging, while supplements sit further down the list as adjuncts.
It's worth being precise about what this trial does and doesn't establish. It's one study, in 120 people, using MRI-measured hippocampal volume as a proxy for brain health rather than a hard clinical outcome like a dementia diagnosis. Effect sizes on the actual memory tests in that trial were modest, and not every subsequent exercise-and-brain-imaging study has replicated the volume finding at the same magnitude. But the direction — aerobic exercise associated with less age-related shrinkage, or outright growth, in a region tightly linked to memory — has shown up across multiple imaging studies and reviews since, which is exactly the kind of convergent, mechanistically-grounded evidence that's largely absent from the supplement literature on cognition.
How that compares to the evidence behind our own products
Our creatine and cognition guide covers a 2024 meta-analysis of 16 RCTs (492 participants) finding real, if moderate-certainty, effects on memory, attention and processing speed.3 Our omega-3 and cognition guide covers a 2025 dose-response meta-analysis of 58 trials finding modest, non-linear effects on several cognitive domains.4 Read side by side with the exercise data, the honest pattern is: exercise's effect size sits in a similar small-to-moderate range as the best-evidenced supplements — it isn't obviously larger on a cognitive test score — but it's supported by a bigger, more consistent evidence base, it has direct structural evidence behind it, and it comes with cardiovascular and metabolic benefits no supplement replicates.
| Intervention | Evidence base | What it shows |
|---|---|---|
| Aerobic/resistance exercise | 50 RCTs, 4,826 people | Small-moderate cognitive gains (g=0.155–0.254); structural hippocampal growth in a dedicated RCT |
| Creatine (discontinued from the Proco range) | 16 RCTs, 492 people | Moderate-certainty gains in memory, attention, processing speed |
| Omega-3 (EPA/DHA) | 58 trials, dose-response | Modest, non-linear effects across several cognitive domains |
Does adding a supplement on top of exercise help?
This is the question we actually care about: if you're already exercising, does layering a supplement on top move the needle further? A 24-week randomized, placebo-controlled trial tested exactly that.5 Older adults were assigned to no exercise plus placebo, exercise (150 minutes/week) plus placebo, or the same exercise program plus a long-chain omega-3 supplement (420 mg/day combined DHA, EPA and arachidonic acid). Across the full sample, adding omega-3 to the exercise program produced no significant additional improvement in cognitive test scores over exercise alone. The one exception was a subgroup of participants with low skeletal muscle mass, where the combined group showed measurably better selective attention and working memory scores than controls — a plausible signal, but a subgroup finding, not the headline result.
We think that result deserves more attention than it usually gets, because it's the closest thing to a direct head-to-head test of the claim this whole article is built around. It isn't a case for skipping omega-3 — sarcopenia risk is common enough in older adults that the subgroup effect is clinically relevant, and the supplement's other benefits (triglycerides, cardiovascular markers) aren't in question here. But for the specific claim "a cognitive supplement will meaningfully add to what exercise already does," this trial is the most direct evidence we could find, and it's a fairly muted result outside of that one subgroup.
Bottom line
If you only have the budget or willpower for one intervention, the evidence says start with training, not a bottle.
None of this is an argument against creatine or omega-3 — the trial evidence for both is real, which is why we carried creatine for as long as we did and why omega-3 remains in the range today. It's an argument against treating either as a substitute for the thing with the strongest, most consistent evidence in this entire category: a structured exercise routine that, in at least one controlled trial, physically grew the brain region most tied to memory. Exercise is the intervention with a dose-response relationship, a plausible mechanism (BDNF and structural growth), and a much larger combined trial base than any single supplement can claim. Supplements are the reasonable next layer on top — not the substitute underneath.
If we're being consistent with how we evaluate every ingredient we sell, we have to apply the same scrutiny to the intervention that isn't a product. Exercise doesn't have a company behind it funding awareness campaigns, so it rarely gets framed as "the highest-evidence option" the way a new supplement launch does — but on the numbers, it is. Our practical recommendation hasn't changed from what the evidence has said for years: get the training in first, at a moderate, sustainable intensity, several times a week. Layer omega-3 on top if the specific evidence for your situation — sarcopenia risk, low dietary intake, a documented gap — makes that a reasonable next step, not as a way to skip the harder part. (Creatine played that same role for a time, before being discontinued from the Proco range.)
This article is for informational purposes only and has not been evaluated by the FDA. It is not intended to diagnose, treat, cure, or prevent any disease. Speak with a healthcare provider before starting any new supplement, especially if you take medication or have an existing health condition.
References
- Effects of exercise on executive function in cognitively healthy older adults: a systematic review and three-level meta-analysis. BMC Public Health, 2026. link.springer.com
- Erickson KI, et al. Exercise training increases size of hippocampus and improves memory. PNAS, 2011. pmc.ncbi.nlm.nih.gov
- Effects of creatine supplementation on cognitive function in adults: systematic review and meta-analysis. 2024. ncbi.nlm.nih.gov
- A systematic review and dose-response meta-analysis of omega-3 supplementation on cognitive function. Scientific Reports, 2025. nature.com
- Effects of combining exercise with long-chain polyunsaturated fatty acid supplementation on cognitive function in the elderly: a randomised controlled trial. Scientific Reports, 2020. nature.com
Related reading: Modifiable Dementia Risk: What the Research Actually Shows
Proco Omega-3 is dosed to the studied range and third-party tested every batch — a reasonable layer on top of training, not a replacement for it. (Proco Creatine Monohydrate was too, before being discontinued from the range.) Shop Omega-3 →