Nootropic Ingredients Guide 2026

A 2009 double-blind, placebo-controlled trial (Mori et al., n=30) found higher cognitive function scores in adults with mild cognitive impairment after 16 weeks of 3g/day; scores fell again within 4 weeks of stopping. Its lead author works for Hokuto Corporation, a mushroom producer. A 2019 multicentre RCT improved MMSE scores but not the two other memory tests. In healthy adults, two small 2023 pilot RCTs found acute gains on Stroop, N-Back and reaction-time tasks at 1–1.8g, and only a non-significant trend toward lower stress after 28 days. The evidence is small-sample and short-term.

A meta-analysis of 9 RCTs (Kongkeaw et al., 2014, n=518) found Bacopa shortened Trail Making B and choice reaction times versus placebo, and two 12-week RCTs in healthy older adults (Calabrese 2008; Morgan & Stevens 2010) improved delayed word recall at 300mg/day. The newest 12-week RCT (Lopresti 2025, n=101, 300mg/day) found no effect on verbal learning, attention or working memory, though it did reduce self-reported stress. A 2026 network meta-analysis of 29 RCTs found ≥600mg/day beat 300–450mg/day for working memory. Best evidence is for delayed recall rather than acute effects.

An RCT in healthy older adults (Spiers et al., 1996) found 1000mg/day improved delayed verbal recall in people with relatively inefficient memory, with 2000mg/day improving immediate and delayed recall. A 2023 meta-analysis found a positive effect on cognitive status in MCI and dementia, but rated study quality poor with a high risk of bias. The 2005 Cochrane review found benefit on memory and behaviour in older adults with chronic cerebral disorders but no evidence of benefit on attention. In acute ischemic stroke, a dose-response RCT (Clark 1997) found better functional outcomes, with 500mg the optimal dose.

A 2026 meta-analysis of 31 RCTs (n=1,168) found a single 200mg dose taken 30–60 minutes before testing improved choice reaction time; its acute stress effect was modest and driven by high-risk-of-bias studies, and anxiety effects were inconsistent. With caffeine, an 11-study meta-analysis (Camfield 2014) found moderate effects versus placebo on alertness and attention-switching accuracy; Kahathuduwa 2016 found additive effects with no interaction, and Foxe 2012 found no added benefit over either compound alone. The one alpha-wave (MEG) trial found higher alpha activity at 2 hours, and only in people with higher trait anxiety.

Small SHR-5 extract trials found less mental fatigue: a 2003 RCT in 161 military cadets after a single dose, a 2000 crossover trial in 56 physicians on night duty over two weeks (Darbinyan et al.), and a 2000 pilot in students during exams. The Swedish burnout RCT (Olsson et al., 2008, n=60, 576mg/day) ran 28 days — not 12 weeks — and improved burnout and attention scores versus placebo, while depression scores improved equally in both groups. A 2012 systematic review of 11 trials rated every included study at high or unclear risk of bias and called the evidence contradictory.

RCTs in older adults with memory complaints or mild cognitive impairment report memory benefits, though often only in subgroups: soy PS at 100–300mg/day for 6 months helped only participants with low baseline scores (Kato-Kataoka 2010), and marine PS-DHA at 300mg/day improved immediate verbal recall in an exploratory 15-week trial (Vakhapova 2010). A 2026 network meta-analysis in MCI/Alzheimer's found PS 100mg improved MMSE but not the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog). In healthy children, a 12-week RCT of 100mg sunflower PS found no effect on primary or secondary outcomes (Friling 2025; authors include staff of IFF, the product's manufacturer). A positive 2024 MCI trial (Duan 2024; BYHEALTH co-authors) gave only 31.5mg PS inside a multi-ingredient formula. The FDA allows two qualified claims, that it may reduce the risk of dementia and that it may reduce the risk of cognitive dysfunction in the elderly, each with the disclaimer that 'FDA concludes that there is little scientific evidence supporting this claim' (FDA letter, 13 May 2003).

A multicenter RCT in mild-to-moderate Alzheimer's dementia (De Jesus Moreno, 2003, n=261) found 1200mg/day improved ADAS-Cog, MMSE and global scores versus placebo at 90 and 180 days, and a 2023 meta-analysis supports benefit in cerebrovascular cognitive impairment. In healthy men, a single 315–630mg dose improved Stroop performance but not N-Back or Flanker (Kerksick 2024). Sports trials are inconsistent: a lower-body force gain after 6 days at 600mg (Bellar 2015), no strength effect at 250–500mg for 7 days, and no power-output effect after a single 630mg dose.

A 2012 RCT in chronically stressed adults (Chandrasekhar et al., KSM-66 600mg/day, 60 days; extract supplied by its maker Ixoreal Biomed) found serum cortisol fell 27.9% versus 7.9% on placebo and perceived stress fell 44%. A 2024 meta-analysis of 9 RCTs confirmed significant reductions in perceived stress, anxiety and cortisol, though a 2019 crossover trial of a low-dose extract in older overweight men found no cortisol effect. A 2017 RCT (Choudhary et al., 300mg twice daily, 8 weeks) improved memory and executive function — in adults with mild cognitive impairment, not healthy adults. Liver-injury case reports exist, and Denmark banned ashwagandha supplements in 2023.

Chinese RCTs show Huperzine A improved memory and learning in Alzheimer's patients (Xu et al., 1995: 58% vs 36% improved at 200mcg/day over 8 weeks) and in adolescent students (Sun et al., 1999: 100mcg/day for 4 weeks). A 2013 meta-analysis of 20 RCTs found significant benefits in Alzheimer's disease, but rated most trials at high risk of bias; the 2008 Cochrane review concluded the evidence is inadequate to recommend it, and a 2012 Cochrane review found no eligible trials in mild cognitive impairment. A 2019 RCT after traumatic brain injury found no memory benefit over placebo.

Military and stress trials found tyrosine reduced performance decline during one night of sleep loss (Neri et al., 1995, 150mg/kg), noise stress (Deijen & Orlebeke, 1994, 100mg/kg) and a combat training course (Deijen et al., 1999, 2g/day) — but neither Deijen trial found any effect on mood. Other trials were null or negative: tyrosine did not protect cognition or performance under exercise heat stress (Coull 2016, 150mg/kg), and 2g worsened cognitive flexibility under high cognitive load (Robson 2019). A 2015 narrative review (Jongkees et al.) concluded benefits are conditional on short-term stress that depletes dopamine and norepinephrine.

A 2016 review (McLellan, Caldwell & Lieberman — a narrative review, not a meta-analysis) found low-to-moderate doses (~40–300mg) consistently improve alertness, vigilance, attention and reaction time, with less consistent effects on memory and executive function. A 2010 Cochrane review of shift workers and a 2026 meta-analysis of 7 military sleep-loss RCTs confirmed gains in attention, vigilance and complex task performance. Side effects rise with dose, and the European Food Safety Authority (EFSA, 2015) sets 200mg per single dose and 400mg/day as safe for healthy adults — 200mg/day for pregnant women.

The NIH-funded GEM trial (DeKosky 2008, n=3,069, 240mg/day, median 6.1 years) found no reduction in dementia or Alzheimer's incidence in people aged 75+. For existing cognitive impairment and dementia, a meta-analysis of 9 RCTs (Tan et al., 2015, 22–26 weeks, mainly 240mg/day EGb 761) found benefits on cognition and daily living, concentrated in patients with neuropsychiatric symptoms. The 2026 Cochrane review of 82 RCTs found small-to-moderate benefits in dementia (low-certainty evidence) but little or no effect in mild cognitive impairment. A 2013 review rated the dementia evidence low quality, noting most trials were pharmaceutical-industry sponsored. Ginkgo raises bleeding risk with warfarin.

DHA is essential for brain development and maintenance, but RCT results are mixed. A 2012 Cochrane review (n=4,080) found no cognitive benefit of omega-3 supplements in cognitively healthy older adults, and a 2025 meta-analysis found no meaningful ADAS-Cog benefit once Alzheimer's has developed. Two 6-month RCTs were positive: 900mg DHA/day improved learning and recognition memory in age-related cognitive decline (Yurko-Mauro et al., 2010 — sponsored by the algal-DHA maker Martek, with a Martek employee as lead author), and 1.16g/day improved memory and working-memory reaction times in healthy adults aged 18–45 with low DHA intake (Stonehouse 2013). A 2021 NIH-funded meta-analysis (n=81,210) found omega-3 supplements raise atrial fibrillation risk, more so above 1g/day.

A 2014 Pycnogenol study (Belcaro et al.) in healthy professionals aged 35–55 reported small but significant cognitive improvements and a 30.4% drop in plasma free radicals after 12 weeks at 150mg/day — but it was a non-randomized product-evaluation registry study, not an RCT. A 2011 controlled (non-randomized) study in students (Luzzi et al.) reported better attention, memory and exam scores over 8 weeks. Both come from the same Irvine3 Labs / Chieti-Pescara author group, which has published numerous Pycnogenol studies; Pycnogenol is a Horphag Research trademark, and these trials are widely reported as industry-supported, though no sponsor is disclosed in the abstracts. The independent 2020 Cochrane review rated the evidence for every pine bark outcome it assessed as very low certainty. A 2025 network meta-analysis ranked Pycnogenol highly for mild cognitive impairment but cautioned about heterogeneity.

A 2003 meta-analysis of double-blind RCTs (Montgomery et al.) found a modest but significant advantage for ALCAR over placebo in mild cognitive impairment and mild Alzheimer's disease at 1.5–3g/day, apparent by 3 months and growing over time. A 2018 meta-analysis of 12 RCTs (Veronese et al., n=791) found a large reduction in depressive symptoms, comparable to antidepressants with fewer adverse effects, most clearly in older adults. A 2022 RCT in pre-frail older adults (3g/day) improved MMSE and walking distance. A 2020 critical review still calls its role in dementia "under debate". No healthy-young-adult trial was found.

Of the trials we reviewed, two name Lutemax 2020 as their material, both run or funded by its maker, OmniActive: a skin-tone trial and a screen-use trial (below); the cognitive evidence comes from lutein and zeaxanthin trials that do not name Lutemax 2020, one of which was funded and supplied by OmniActive (Stringham 2019). In healthy young adults, 12mg/day for 12 months raised MPOD and improved visual memory (Renzi-Hammond 2017 — co-authored by Abbott Nutrition staff, with material from DSM, a Lutemax competitor); 22mg/day for 12 months improved memory in adults with low macular pigment (Power 2018, funded by the European Research Council); and 13–27mg/day for 6 months improved memory, attention and processing speed (Stringham 2019, funded by OmniActive, which supplied the supplements). A 2023 meta-analysis found xanthophylls speed photostress (glare) recovery, and two OmniActive-funded trials also reported better glare and photostress recovery versus placebo: the screen-use trial below and a 12-month trial in 59 young adults (Stringham 2016). The maker's skin trial (Juturu 2016; two of three authors employed by OmniActive, which makes Lutemax) tested skin tone, not cognition. For screen-related eye symptoms the two trials disagree: in 48 students with 6+ hours of daily screen time, 24mg/day of the Lutemax 2020 formulation for 6 months reduced self-rated eye strain, eye fatigue and headache frequency and improved sleep quality versus placebo (Stringham 2017; funded by OmniActive, and the first author consults for it), though a separate report by OmniActive staff on a 48-person, 24mg/day, 6-month trial of the same design found the sleep difference significant at 3 months but not at 6 months (Culver 2018, not indexed in PubMed); in 70 heavy screen users a different lutein/zeaxanthin product (Lute-gen, 10mg lutein + 2mg zeaxanthin isomers; funded by its supplier, Bio-gen Extracts) improved tear production, tear-film stability and photo-stress recovery over 6 months, but self-rated eye strain, visual fatigue, sleep and attention did not differ from placebo (Lopresti & Smith 2025).

Four small RCTs, all with manufacturer involvement: a 2011 trial (Berry et al.) in elderly people with below-average cognition found a single 1600mg dose reduced Stroop errors, but 2400mg did no better than placebo; a 2012 trial by the same group found 1500mg/day for 12 weeks had no effect on any cognitive measure in healthy older adults (material supplied by Frutarom); a 2015 trial (Kennedy et al., two Frutarom employees as co-authors) found 800mg improved speed, delayed recall and executive function in adults 40–65 with memory complaints, concluding the optimal dose is at or below 800mg; and a 2020 trial (Kennedy et al., two Anklam Extrakt employees as co-authors) found 430–1290mg improved working memory and multitasking over 4 weeks, with no effect on mood.

The largest and most independent trial (Dodd et al., 2024, n=114, Northumbria University with a PepsiCo co-author) gave a single 300mg dose of mango leaf extract and found no cognitive benefit — participants made more subtraction errors than on placebo. An earlier pilot (López-Ríos et al., 2020, n=16, all four authors Nektium employees) used 500mg, not 300mg, and found only a marginal reaction-time signal. Two sprint trials (2018, 2019; lead authors affiliated with Nektium, the manufacturer) combined 140mg with quercetin or luteolin and improved sprint power output, but measured no cognitive outcome. Three of the four trials are manufacturer-authored.

Only three human RCTs have tested methylliberine. The only one measuring cognition with methylliberine alone (La Monica et al., 2023, n=25, 100mg/day) found better self-rated concentration, motivation, mood and energy, but a negligible effect on objective cognitive tests (Stroop, Trail Making B). A 4-week safety trial (VanDusseldorp et al., 2020, n=125, 100–150mg/day) found no clinically significant cardiovascular or blood changes; it did not test cognition. A third trial (Cintineo 2022) tested it only inside a caffeine + theacrine combination. Both methylliberine-specific trials were funded in whole or part by Compound Solutions, which sells Dynamine, and a La Monica co-author holds patents on methylliberine.

Four randomized, placebo-controlled trials have tested Longvida on cognition. Two from the same research group were positive at 400mg/day: in 60 healthy adults aged 60–85 (Cox et al., 2015), sustained attention and working memory improved 1 hour after a single dose, and working memory and mood after 4 weeks; in 80 adults aged 50–80 (Cox et al., 2020, funded by Longvida's maker Verdure Sciences), working memory was better at 12 weeks and fatigue lower at 4 and 12 weeks. Two trials funded by the US National Institutes of Health, with capsules supplied by Verdure Sciences, gave 2000mg/day and found no cognitive benefit: 12 weeks in 39 healthy adults aged 45–74 (Santos-Parker et al., 2018) and 12 months in 88 adults with chronic kidney disease (Gimblet et al., 2024). The positive results have not been repeated by an independent group.

Reviews rate the sleep evidence as low to very low certainty. A 2026 systematic review of 12 RCTs (Lopresti et al.) concluded that the evidence does not support magnesium as a routine treatment for insomnia, though it may modestly improve some subjective outcomes in some adults, and a 2021 meta-analysis of 3 trials in 151 older adults (Mah & Pitre) found sleep onset about 17 minutes faster than on placebo, with no significant change in total sleep time. Individual trials split: 250mg/day of elemental magnesium as bisglycinate lowered insomnia scores slightly more than placebo over 4 weeks in 155 adults with poor sleep (Schuster et al., 2025; effect size d=0.2), 500mg/day as magnesium oxide helped 46 older adults with insomnia (Abbasi et al., 2012), and 320mg/day as citrate did no better than placebo in 100 adults over 51 (Nielsen et al., 2010). The two L-threonate trials cited here were funded by companies that make or supply the ingredient. Our review graded the evidence for stress, mood and cognition as preliminary.

The evidence is small, short and mixed, and every positive single-ingredient sleep result used juice or concentrate. In two crossover pilots in older adults with insomnia, 240mL of juice twice daily for 2 weeks lowered insomnia severity and night-time waking but not time to fall asleep (Pigeon et al., 2010, n=15, funded in full by the juice maker CherryPharm), or added 84 minutes of total sleep time on polysomnography in 8 completers with no change in sleep onset or waking (Losso et al., 2018, funded by the Cherry Marketing Institute with NIH grants). In 20 healthy adults, concentrate increased time in bed, total sleep time and sleep efficiency over 7 days (Howatson et al., 2012), but a 30-day trial of juice and capsules in 44 healthy adults found no sleep difference (Hillman 2026). 500mg/day of tart cherry powder for 14 days had no effect on any sleep measure in 34 adults with poor sleep and overweight or obesity (Tucker 2024, funded by the Cherry Marketing Institute). No meta-analysis was found.

NR raises NAD+ in human blood: in an 8-week trial in 140 healthy overweight adults, whole-blood NAD+ rose 22%, 51% and 142% at 100, 300 and 1,000mg/day (Conze et al., 2019, funded by ChromaDex), and the rise has been reproduced by other groups, including Nestlé researchers. That is a biomarker, not a health outcome. No randomized cognition trial in healthy adults was found. Three placebo-controlled trials in mild cognitive impairment or subjective cognitive decline (1,000mg/day for 8–12 weeks) and a long-COVID trial (2,000mg/day) found no cognitive benefit, even though blood NAD+ rose 2- to 3-fold. In the largest trial, NOPARK (410 people with early Parkinson's disease, 1,000mg/day for 52 weeks, published in JAMA in 2026), symptom scores worsened more on NR than on placebo. A 2023 review of 25 human studies concluded that oral NR has shown few clinically relevant effects. Most NR trials are funded, supplied or co-authored by ChromaDex/Niagen Bioscience or Elysium Health.

The trials are small and short. A 2022 meta-analysis that could pool only 4 trials (Sutanto et al.) found shorter time awake after falling asleep, larger at 1g/day or more, and no effect on other sleep measures. In a 3-week trial in 57 adults with chronic insomnia, tryptophan taken with carbohydrate improved sleep while carbohydrate alone did not (Hudson et al., 2005; the dose is not in the abstract). For mood, a 2021 review found differences from placebo in 4 of 11 RCTs in healthy adults (Kikuchi et al.). No trial found a cognitive benefit in healthy adults, and a 2010 review found that tryptophan loading slows reaction time. Funding could not be checked for most trials. The 1989 eosinophilia-myalgia syndrome (EMS) epidemic was traced to tryptophan from a single manufacturer.

The best sleep evidence is for one branded extract. Two placebo-controlled trials of the phospholipid-carrier extract Relissa at 400mg/day found better sleep: in a 2-week crossover in 30 adults, insomnia scores were 2.9 points lower than on placebo (Di Pierro 2024, whose authors include the scientific director of and consultants to Pharmextracta, maker of the tested product), and in a 3-week trial in 100 adults with emotional distress or poor sleep, sleep quality improved, though the treated group started with worse sleep (Bano 2023). An open-label study without placebo found half the sleep-score change at 200mg/day as at 400mg/day (−15% vs −30%). A formula of L-theanine, lemon balm, valerian and saffron was no better than placebo over 6 weeks (Gutiérrez-Romero 2024). In single-dose tests in 20 healthy young adults, the lowest dose raised calmness early, but the highest dose lowered alertness and some doses worsened memory scores (Kennedy 2002), and the largest cognition trial (323 older adults, 96 weeks) found no effect on its primary endpoint (Noguchi-Shinohara 2023).