Nootropics: which 5 substances have been best researched?
Short answer: Nootropics are substances studied for their effects on attention, memory, or reaction time. Among well-known nootropics, caffeine is the best studied: in studies, low to moderate doses of about 40 to 300 mg were associated with better alertness and reaction time (McLellan et al., 2016). For guarana, creatine, omega-3, and L-carnitine, the effects found are smaller or inconsistent. EFSA considers up to 400 mg of caffeine per day safe for healthy adults.
Last updated: October 26, 2026 · Written by Florian Fermin
Nootropics sounds like something from a tech podcast. When you compare the studies, the list is shorter than the marketing suggests. That's why I've listed five well-known substances here, along with what's been studied in people and what's still uncertain.
What exactly are nootropics?
Nootropics are substances or supplements studied for their effects on brain functions such as attention, memory, reaction time, or mental fatigue. The word says nothing about how well something works. Nootropics include familiar substances such as caffeine and creatine, as well as herbs and substances that have been little studied.
Whether a substance has an effect also depends on your starting point. Sleep, diet, stress, and how sensitive you are to caffeine all play a part. So you can't simply apply the results of a study to yourself.
Which nootropics have been best studied in healthy people?
In healthy adults, caffeine is the best studied, followed by creatine and guarana. For omega-3, most research focuses on older adults, and for L-carnitine, mainly on people with memory problems. The table shows what has been studied for each substance, in whom, and how strong the evidence is.
| Substance | What was studied | Amount in studies | For whom | How strong |
|---|---|---|---|---|
| Caffeine | Alertness, attention, reaction time | Approximately 40-300 mg | Healthy adults | Many studies, consistent |
| Creatine | Short-term memory, reasoning | 5 g per day in the best-known study | Healthy adults, mainly vegetarians | 6 studies, 281 participants, varies by area |
| Guarana | Reaction time and accuracy | 37.5-500 mg guarana (4.3-100 mg caffeine) | Healthy adults | 8 studies, 328 participants, small effect on reaction time |
| Omega-3 (DHA and EPA) | General cognition, memory | Varies by study | Mainly older adults | No effect on general cognition, slight effect on memory |
| L-carnitine (acetyl-L-carnitine) | Memory with memory problems | 1.5-3 g per day | Older adults with memory problems | Role still under discussion |
What does caffeine do for your alertness, and how much caffeine is safe per day?
Caffeine blocks adenosine receptors in your brain, making you feel less sleepy. In studies, doses of around 40 to 300 mg were associated with better alertness, attention, and reaction time. According to EFSA, up to 400 mg per day is safe for healthy adults, with a maximum of 200 mg at a time.
Effects on memory and more complex tasks, such as decision-making, were less consistent (McLellan et al., 2016). So more is not better. A high intake can cause restlessness or disrupt your sleep.
For pregnant women, EFSA recommends a maximum of 200 mg per day from all sources combined (EFSA, 2015). So add up coffee, tea, energy drinks, and caffeine from supplements.
L-theanine, an amino acid from tea, has been tested together with caffeine in several studies; which amounts were used is explained in L-theanine dosage.
Is guarana different from caffeine, or does it amount to the same thing?
Guarana is a plant whose seeds naturally contain caffeine. In a meta-analysis of 8 studies with 328 participants, people responded slightly faster with guarana than with placebo, with no difference in accuracy. Whether this was due to caffeine or other substances is unknown.
The amounts used ranged from 37.5 to 500 mg of guarana, with 4.3 to 100 mg of caffeine (Hack et al., 2023). An older study with 129 young adults tested guarana together with vitamins and minerals. As a result, it is not possible to say which part made the difference (Kennedy et al., 2008).
Read more about the plant and the caffeine it contains in what is guarana.
Why is creatine, known from the gym, also being studied as a nootropic?
Creatine plays a role in cells’ energy supply, including in the brain. In a systematic review of 6 studies with 281 healthy people, creatine appeared to improve short-term memory and reasoning. Results for other areas, such as attention and reaction time, were mixed.
Vegetarians performed better than meat eaters on memory tasks in that review (Avgerinos et al., 2018). In the best-known study, 45 vegetarians took 5 grams of creatine per day for six weeks. Their scores on working memory and an intelligence test increased compared with placebo (Rae et al., 2003).
Scores remained unchanged in young people in the review. Read 5 facts and myths about creatine for general facts and myths about creatine.
What does research say about omega-3 and memory?
Omega-3 fatty acids such as DHA and EPA are found mainly in oily fish and algal oil. In a meta-analysis of 25 studies, omega-3 had no effect on general cognition in adults without dementia, and a slight effect on memory. Most research concerns older adults, not young people looking to improve their focus.
That meta-analysis found an effect size of virtually zero for general cognition (Alex et al., 2020). In another review, 7 of the 15 studies in healthy people over 55 found a beneficial result, while 8 did not (Welty, 2023).
Omega-3 is not a quick pick-me-up like caffeine. If you eat little oily fish, it's mainly a dietary issue.
What about L-carnitine as a nootropic?
L-carnitine is a substance your body makes itself and plays a role in the energy metabolism of cells. Research on memory mainly concerns acetyl-L-carnitine in older adults with memory problems, and its role is still under debate. We found no strong research for healthy people looking to improve their focus.
A 2003 meta-analysis found a small difference compared with placebo at doses of 1.5 to 3 grams per day (Montgomery et al., 2003). A more recent review concludes that better studies are needed before any conclusions can be drawn (Pennisi et al., 2020).
What should you look for when buying nootropics in the Netherlands?
Check the amount per serving, your total daily caffeine intake, and whether the ingredients and claims on the label match what has been studied. A formula with ten ingredients in small amounts tells you little. Compare the dosage with the amounts used in studies, as shown in the table above.
- Adding up caffeine. Guarana, green tea, and energy drinks also contain caffeine. Keep your total below 400 mg per day.
- Dosages. If it only says "blend" without amounts for each substance, you don't know what you're getting.
- Claims. In the EU, health claims on labels are subject to strict regulations. Big promises about your brain are a reason to take a closer look. In our focus and concentration collection, you can see which claim is permitted for each product.
- Medications. If you take medication, are pregnant, or are breastfeeding, consult your doctor or pharmacist first.
If you're looking for information on vitamins and minerals for fatigue in addition to focus, read supplements and energy. Products for which an energy claim applies, such as biotin and yerba maté, are in our supplements for energy and vitality.
Summary in 3 points
- Caffeine is the best-studied nootropic: 40 to 300 mg was associated with better alertness and reaction time, and EFSA considers 400 mg per day safe.
- Creatine and guarana showed small or mixed effects in reviews involving 281 and 328 participants.
- For omega-3 and L-carnitine, most of the research concerns older adults. The evidence in healthy young people is limited.
Frequently asked questions
Which nootropic has been studied the most?
Caffeine. It has been studied extensively, and low to moderate doses were consistently associated with better alertness and reaction time. The results for memory and more complex tasks were less clear.
Are nootropics safe?
It varies by substance and dosage. For caffeine, EFSA recommends 400 mg per day for healthy adults and 200 mg for pregnant women. If you take medication, consult your doctor or pharmacist first.
Do nootropics work immediately?
Caffeine and guarana were tested in studies within a few hours of intake. Creatine was given for six weeks in the best-known study.
Is guarana stronger than coffee?
That depends on the amount of caffeine per serving. In studies, the caffeine from guarana ranged from 4.3 to 100 mg. Check the label to see how much caffeine it contains and add it to your coffee intake.
What is the difference between L-carnitine and acetyl-L-carnitine?
Acetyl-L-carnitine is a form of L-carnitine with an acetyl group. Research on memory mainly focuses on this form, and on older adults with memory problems.
Sources
- McLellan TM, Caldwell JA, Lieberman HR (2016). A review of caffeine's effects on cognitive, physical and occupational performance. Neuroscience and Biobehavioral Reviews, 71, 294-312. Europe PMC 27612937
- EFSA (2015). Caffeine. Topic page and scientific advice on the safety of caffeine, May 27, 2015. efsa.europa.eu, accessed October 26, 2026.
- Hack B, Penna EM, Talik T, Chandrashekhar R, Millard-Stafford M (2023). Effect of Guarana (Paullinia cupana) on Cognitive Performance: A Systematic Review and Meta-Analysis. Nutrients, 15(2), 434. Europe PMC 36678305
- Kennedy DO, Haskell CF, Robertson B, et al. (2008). Improved cognitive performance and mental fatigue following a multi-vitamin and mineral supplement with added guaraná (Paullinia cupana). Appetite, 50(2-3), 506-513. Europe PMC 18077056
- Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D (2018). Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Experimental Gerontology, 108, 166-173. Europe PMC 29704637
- Rae C, Digney AL, McEwan SR, Bates TC (2003). Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proceedings of the Royal Society B, 270(1529), 2147-2150. Europe PMC 14561278
- Alex A, Abbott KA, McEvoy M, Schofield PW, Garg ML (2020). Long-chain omega-3 polyunsaturated fatty acids and cognitive decline in non-demented adults: a systematic review and meta-analysis. Nutrition Reviews, 78(7), 563-578. Europe PMC 31841161
- Welty FK (2023). Omega-3 fatty acids and cognitive function. Current Opinion in Lipidology, 34(1), 12-21. Europe PMC 36637075
- Montgomery SA, Thal LJ, Amrein R (2003). Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. International Clinical Psychopharmacology, 18(2), 61-71. Europe PMC 12598816
- Pennisi M, Lanza G, Cantone M, et al. (2020). Acetyl-L-Carnitine in Dementia and Other Cognitive Disorders: A Critical Update. Nutrients, 12(5), 1389. Europe PMC 32408706
This article is for informational purposes and is not medical advice. Dietary supplements are not a substitute for a varied and balanced diet and a healthy lifestyle. If in doubt, during pregnancy, or when taking medication, consult your doctor or pharmacist.
