Herbs and Supplements for Memory: What the Trials Show

Herbs Supplements Methylene blue Heavy metals Sleep Movement FAQ

Memory changes with age, and a long list of herbs and supplements are sold for it. This article covers the ones with human trials behind them, what each trial measured, who paid for it, and where the evidence stops. It also covers the two habits with the strongest data of all, sleep and daily movement, and how to lower everyday exposure to the metals that accumulate in brain tissue.

Key takeaways

• Bacopa and huperzine A carry the most human trial data. Both show measurable effects on specific tests, and both sets of trials have quality problems.
• The largest ginkgo trial ever run, with 3,069 adults over six years, found no reduction in dementia.
• Gotu kola did not differ from placebo on any memory measure in the only meta-analysis. It did raise alertness scores.
• Several supplement trials were run or funded by the company selling the product. Those are marked in the text.
• Sleep and regular movement have larger and more consistent effects on memory than any supplement on this list.

This article is educational and does not provide medical advice. Memory changes have many causes, and a practitioner should evaluate a change that is new, rapid, or affects daily life, since several items below interact with prescription medications and nothing here replaces that conversation.

How to read this list

Evidence: editorial note

Each entry names the strongest human study available, states what it measured, and states its size. A test score is not the same as day-to-day memory, and a study of people with diagnosed cognitive impairment does not tell you what happens in a healthy adult. Where a manufacturer funded or authored a trial, that is stated in the same sentence as the result.

Herbs studied for memory

Evidence: meta-analyses and randomized trials, quality varies by herb

Huperzine A (Huperzia serrata)

Huperzine A is an alkaloid from Chinese club moss. It inhibits acetylcholinesterase, the enzyme that breaks down acetylcholine, which is the same mechanism as the prescription drug donepezil. A 2013 meta-analysis pooled 20 randomized trials with 1,823 participants, all in people with Alzheimer's disease, and found higher scores on the Mini-Mental State Examination at 8, 12, and 16 weeks compared with placebo. The authors rated most of the trials as high risk of bias and said the findings should be read with caution.¹ No trials in healthy adults were included. My teacher KP Khalsa describes it for short-term recall lapses, the misplaced keys kind, which is a clinical observation rather than a trial result. Because it acts on acetylcholine, it should not be combined with cholinesterase inhibitor drugs without a prescriber's input.

Bacopa (Bacopa monnieri)

Bacopa has the longest record in Ayurveda and the cleanest trial data on this list. A 2014 meta-analysis of nine randomized trials with 437 participants found faster performance on the Trail Making Test B and shorter choice reaction time compared with placebo. The authors described the effect as improved speed of attention and called for a head-to-head trial against an existing medication before drawing conclusions about memory itself.² The trials used standardized extracts taken for 12 weeks, and effects appeared late rather than early. Stomach upset is the common complaint in the trial reports.

Gotu kola (Centella asiatica)

Gotu kola is eaten as a leafy green across South and Southeast Asia and has a reputation as a brain tonic. A 2017 systematic review found five randomized trials of gotu kola alone and six of products containing it. Pooled, there was no significant difference from placebo in any cognitive domain. Alertness scores were higher one hour after a dose, and anger scores were lower.³ The authors noted that doses, preparations, and standardization varied widely between trials. Its water-soluble triterpenes make an infusion a sensible preparation, and it appears in my article on herbal support after brain injury for that reason.

Ginkgo (Ginkgo biloba)

Ginkgo is the most-studied herb for memory, and the largest trial answered the main question. The Ginkgo Evaluation of Memory study enrolled 3,069 adults aged 75 and older, gave half of them 120 mg of the EGb 761 extract twice daily, and followed them for a median of 6.1 years. Dementia developed at the same rate in both groups.⁴ The extract was supplied by its manufacturer, Schwabe, and the trial was funded by the National Institutes of Health. Smaller and shorter trials have reported changes on attention tests, which is why ginkgo still appears in supplement blends. Ginkgo affects platelet function and is on the list of botanicals to stop before surgery.

Lion's mane (Hericium erinaceus)

Lion's mane contains hericenones and erinacines, compounds that raise nerve growth factor in cell and animal studies. The human evidence is one small trial. Thirty Japanese adults aged 50 to 80 with mild cognitive impairment took 3 grams of dried mushroom powder daily for 16 weeks. Scores on the Hasegawa Dementia Scale rose in the mushroom group and fell back toward baseline four weeks after they stopped.⁵ The lead author was employed at Hokuto Corporation, a commercial mushroom producer, and a 30-person trial with an industry author needs replication before it carries much weight.

Supplements studied for memory

Evidence: single randomized trials, several manufacturer-funded

Phosphatidylserine

Phosphatidylserine is a phospholipid concentrated in nerve cell membranes. Early trials in the 1990s used a bovine brain extract that is no longer sold; current products are made from soy or sunflower lecithin. The main soy trial randomized 78 Japanese adults aged 50 to 69 with memory complaints to 100 mg, 300 mg, or placebo daily for six months and reported better delayed verbal recall in the supplement groups.⁶ The authors were employees of Yakult, which manufactures the ingredient.

Alpha-GPC

Alpha-glycerylphosphorylcholine supplies choline, the raw material for acetylcholine. The largest trial gave 400 mg three times daily to 261 people with mild to moderate Alzheimer's disease for 180 days and reported higher cognitive test scores than placebo.⁷ The trial was sponsored by Italfarmaco, which sells alpha-GPC as a prescription drug in Italy, and trials in healthy adults are small and short.

Acetyl-L-carnitine

Acetyl-L-carnitine moves fatty acids into mitochondria and donates acetyl groups for acetylcholine synthesis. A Cochrane review of the dementia trials found no benefit on cognition, severity, or daily function, and said the one positive signal on a clinical impression scale may have been chance.⁸ Several of the included trials were unpublished reports held on file by Sigma-Tau, the manufacturer. There are no trials in people without a diagnosis.

DHA from fish

DHA is the main omega-3 fat in brain tissue. The MIDAS trial gave 900 mg of algal DHA daily to 485 adults over 55 with age-related memory complaints for 24 weeks and reported fewer errors on a paired-associate learning test.⁹ Martek, the DHA manufacturer, funded the trial and employed most of its authors. Fish such as sardines and mackerel supply DHA with less oxidation than a capsule that has sat on a shelf, which is the position taken across the bioenergetic food guidance on this site.

L-theanine

L-theanine is the amino acid in green tea and matcha that softens the stimulant effect of caffeine. Electroencephalography studies show increased alpha-wave activity within an hour of a 50 mg dose, a pattern associated with relaxed attention.¹⁰ That study came from Unilever's research institute. Trials of theanine alone on memory are few, and most of the published work pairs it with caffeine and was funded by tea or ingredient companies. The defensible claim is a change in the quality of alertness, since recall has not been tested at dietary doses.

CoQ10

Coenzyme Q10 carries electrons in the mitochondrial respiratory chain, and blood levels fall with age and with statin use. I could not find a controlled human trial of CoQ10 on memory in healthy adults. It is included here so readers know that the mechanistic story has not been tested for this purpose.

Methylene blue: experimental, with drug interactions

Evidence: one 26-person imaging trial, prescribing information

Methylene blue is a synthetic dye used as a prescription drug for methemoglobinemia. At low doses it acts as an alternative electron carrier in mitochondria. A randomized trial at the University of Texas gave 26 healthy adults a single low oral dose or placebo and scanned them during memory tasks. The methylene blue group showed increased activity in prefrontal and parietal regions and answered 7 percent more retrieval questions correctly.¹¹ That is one dose in 26 people, with no data on repeated use.

Two safety points are on the prescribing label. Methylene blue is a monoamine oxidase inhibitor and has caused serotonin syndrome, some cases fatal, in people taking SSRIs, SNRIs, and related drugs. It is also contraindicated in G6PD deficiency, where it can trigger hemolysis.¹² Anyone taking a psychiatric medication should treat it as a prescriber-only decision.

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Lowering everyday heavy metal exposure

Evidence: independent consumer testing, exposure reduction rather than detox

Lead, aluminum, and mercury accumulate in tissue, and lead in particular is well documented to affect memory at blood levels once considered safe. The useful step is cutting the daily sources. Chelation therapy mobilizes stored metals, is a clinical procedure with its own risks, and has caused deaths when done outside medical supervision, so it is not covered here.

• Cookware and dishes. Lead Safe Mama, an independent tester using X-ray fluorescence, has published results on thousands of consumer items. Vintage Pyrex and other milk-glass bakeware test at hundreds to tens of thousands of parts per million of lead in the exterior paint and the glass itself.¹³ Plain stainless steel and bare cast iron test clean in her database.
• Tap water. Homes built before 1986 may have lead solder or lead service lines. A certified lab test costs about $30 and settles the question for your address.
• Aluminum. Antiperspirants, many baking powders, and uncoated aluminum cookware used with acidic food are the common daily sources, and each has an easy substitute.
• Large fish. Mercury concentrates up the food chain. Sardines and mackerel supply the same DHA as tuna and swordfish at a fraction of the mercury.

Sleep and memory

Evidence: physiological review, consistent across decades of research

Memory consolidation happens during sleep. Slow-wave sleep replays the day's hippocampal activity and transfers it to cortical storage, and a 2013 review in Physiological Reviews summarized several hundred human and animal studies showing that both a full night and a daytime nap improve retention of material learned beforehand, an effect no supplement on this list matches.¹⁴ A fixed bedtime, a dark room, and no screens in the last hour are the standard recommendations in that literature. Thyroid function is also one of the first things a practitioner checks when both sleep and memory change together, and the thyroid article on this site explains why.

Daily movement

Evidence: one-year randomized trial with brain imaging

A randomized trial at the University of Illinois assigned older adults to either walking three times a week or stretching for one year, with 120 participants completing all three brain scans. The walking group's anterior hippocampus grew by 2 percent, reversing 1 to 2 years of expected age-related shrinkage by the authors' estimate, and the change tracked with blood levels of brain-derived neurotrophic factor.¹⁵ The stretching group lost volume over the same period. The walking group did 40 minutes three days a week, with no gym involved.

Frequently asked questions

Evidence: summarized from the sections above

Which herb has the strongest evidence for memory?

Bacopa. A meta-analysis of nine randomized trials found faster attention and reaction time scores over 12 weeks. Huperzine A has more trials, but they are all in Alzheimer's patients and most were rated high risk of bias.

Does ginkgo biloba improve memory?

The largest trial, with 3,069 adults over six years, found no reduction in dementia and no difference in cognitive decline. Shorter trials report small changes on attention tests. Ginkgo also affects platelet function.

Is lion's mane proven to help memory?

Not yet, since the one 16-week trial in 30 adults with mild cognitive impairment showed higher test scores that faded after stopping, the lead author worked for a mushroom producer, and the result has not been replicated at scale.

Footnotes

1. Yang G, Wang Y, Tian J, Liu JP. Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One. 2013;8(9):e74916. doi:10.1371/journal.pone.0074916. ↩
2. Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, Limpeanchob N, Scholfield CN. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. J Ethnopharmacol. 2014;151(1):528-535. doi:10.1016/j.jep.2013.11.008. ↩
3. Puttarak P, Dilokthornsakul P, Saokaew S, et al. Effects of Centella asiatica (L.) Urb. on cognitive function and mood related outcomes: a systematic review and meta-analysis. Sci Rep. 2017;7:10646. doi:10.1038/s41598-017-09823-9. ↩
4. DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA. 2008;300(19):2253-2262. doi:10.1001/jama.2008.683. Extract supplied by Schwabe Pharmaceuticals; funded by NIH. ↩
5. Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytother Res. 2009;23(3):367-372. doi:10.1002/ptr.2634. Lead author affiliated with Hokuto Corporation. ↩
6. Kato-Kataoka A, Sakai M, Ebina R, Nonaka C, Asano T, Miyamori T. Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints. J Clin Biochem Nutr. 2010;47(3):246-255. doi:10.3164/jcbn.10-62. Authors employed by Yakult. ↩
7. De Jesus Moreno Moreno M. Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial. Clin Ther. 2003;25(1):178-193. doi:10.1016/S0149-2918(03)90023-3. Sponsored by Italfarmaco. ↩
8. Hudson S, Tabet N. Acetyl-L-carnitine for dementia. Cochrane Database Syst Rev. 2003;(2):CD003158. doi:10.1002/14651858.CD003158. Several included trials were unpublished Sigma-Tau reports. ↩
9. Yurko-Mauro K, McCarthy D, Rom D, et al. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement. 2010;6(6):456-464. doi:10.1016/j.jalz.2010.01.013. Funded by Martek Biosciences; most authors Martek employees. ↩
10. Nobre AC, Rao A, Owen GN. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr. 2008;17 Suppl 1:167-168. PMID 18296328. Unilever Food and Health Research Institute. ↩
11. Rodriguez P, Zhou W, Barrett DW, et al. Multimodal randomized functional MR imaging of the effects of methylene blue in the human brain. Radiology. 2016;281(2):516-526. doi:10.1148/radiol.2016152893. ↩
12. ProvayBlue (methylene blue injection) prescribing information, Contraindications and Warnings and Precautions 5.1 and 5.3. DailyMed. ↩
13. Rubin T. Please stop using vintage Pyrex glassware for cooking and serving food. Lead Safe Mama. tamararubin.com. Independent XRF testing. ↩
14. Rasch B, Born J. About sleep's role in memory. Physiol Rev. 2013;93(2):681-766. doi:10.1152/physrev.00032.2012. ↩
15. Erickson KI, Voss MW, Prakash RS, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci USA. 2011;108(7):3017-3022. doi:10.1073/pnas.1015950108. ↩