At NeuroVesa we value science and evidence. That's why we we went through and summarized a collection of the studies on the ingredients in eudopa™.

CDP-Choline (Citicoline)

Study: Nakazaki E, Mah E, Sanoshy K, Citrolo D, Watanabe F.C (2021) Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial - PubMed. J Nutr  Aug 7;151(8):2153-2160.

  • Findings: 12 weeks of 500 mg/day supplementation of citicoline improved overall memory performance, especially episodic memory, in healthy older males and females with age related memory impairment. 

Study: McGlade E, Agoston AM, DiMuzio J, Kizaki M, Nakazaki E, Kamiya T, Yurgelun-Todd D (2019). The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males - PubMed  J Atten Disord. Jan;23(2):121-134. doi: 10.1177/1087054715593633. Epub 2015 Jul 15. PMID: 26179181.

  • Findings: 75 adolescent males receiving 250 mg or 500 mg of citicoline for four weeks showed enhanced attention, impulse control, and motor speed vs placebo in healthy adolescent males, with the higher dose (500 mg) being most effective. 

Study: Al-Kuraishy HM, Al-Gareeb AI (2020) Citicoline Improves Human Vigilance and Visual Working Memory: The Role of Neuronal Activation and Oxidative Stress. Basic and clinical neuroscience.

  • Findings: 2 weeks of 500mg/day citicoline improved human psychomotor vigilance, arousal, and visual working memory with significant amelioration of oxidative stress compared with placebo.

Study: Świątkiewicz M, Grieb P (2023)  Citicoline for Supporting Memory in Aging Humans - PMC.  Aging Dis PMID: 37196134

  • Findings (Authors conclusion): “These observations provide further confirmation that citicoline shall be seriously considered as an agent providing support for failing memory in middle-aged and elderly persons”

Study: Spiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ (1996). Citicoline Improves Verbal Memory in Aging | JAMA Neurology Arch Neurol. 

  • Findings: Subjects aged 50-85 were given 1000 mg/day citicoline for 3 months. Improvements in delayed recall on logical memory were seen with subjects with relatively inefficient memories. Subjects taking 2000 mg/day citicoline for 2 months also saw improvements in immediate and delayed logical memory vs placebo.

Study: Silveri MM, Dikan J, Ross AJ, Jensen JE, Kamiya T, Kawada Y, Renshaw PF, Yurgelun-Todd DA (2008) Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy - PubMed NMR Biomed PMID:18816480

  • Findings: 16 healthy subjects taking 500 mg/day or 2000 mg/day Cognizin citicoline for 6 weeks showed improvements in frontal lobe activation and altered phospholipid membrane turnover. Citicoline supplementation may therefore help mitigate cognitive decline associated with aging, as well as increase the amount of essential phospholipid membrane components needed to maintain healthy cell membranes.

Study: Alvarez XA, Laredo M, Corzo D, Fernández-Novoa L, Mouzo R, Perea JE, Daniele D, Cacabelos R (1997) Citicoline improves memory performance in elderly subjects - PubMed  Methods Find Exp Clin Pharmacol. PMID: 9203170.

  • Findings: 24 subjects with age related memory impairments given 500 mg/day and 1000 mg/day citicoline for 4 weeks showed improvements in memory performance during free recall tasks. Citicoline might work to improve memory by acting on mechanisms of brain neurotropism (stimulating nerve maturation) and cerebrovascular regulation (improving blood pressure/blood flow).

Studies: 

1. Gudi V, Grieb P, Linker RA, Skripuletz T (2023) . CDP-choline to promote remyelination in multiple sclerosis: the need for a clinical trial Neural Regen Res. PMID: 37449595

2. Skripuletz T, et al. (2015). Pivotal role of choline metabolites in remyelination - PubMed  Brain.. PMID: 25524711. 

3. Gudi V, Schäfer N, Gingele S, Stangel M, Skripuletz T (2021) Regenerative Effects of CDP-Choline: A Dose-Dependent Study in the Toxic Cuprizone Model of De- and Remyelination - PMC : Pharmaceuticals (Basel).

4. Grieb P, Świątkiewicz M, Kamińska A, Jünemann A, Rejdak R, Rejdak K (2021). Citicoline: A Candidate for Adjunct Treatment of Multiple Sclerosis - PMC  Pharmaceuticals (Basel). PMID: 33918331

  • Findings:  Remyelination relies heavily on choline metabolism, especially phospholipids required for myelin synthesis. Supplementing with CDP-choline (citicoline) increases choline metabolites and can increase the number of and boost OPC (oligodendrocyte precursor cell) activity and accelerate remyelination in animal models. These mechanisms have potential to help with MS related symptoms in humans.

Study: Abushukur Y, Knackstedt R. The Cureus. (2022) The Impact of Supplements on Recovery After Peripheral Nerve Injury: A Review of the Literature - PMC. The Cureus.

  • Findings: a review of studies utilizing CDP-choline administration in rat subjects resulted in decreased scar formation and nerve adherence to surrounding tissue. Citicoline also improved sciatic nerve functional recovery, increased amplitude of the muscle action potential, axonal organization, axonal counts, axonal density, and axonal myelination.

Study: Bruce SE, Werner KB, Preston BF, Baker LM (2014). Improvements in Concentration, Working Memory, and Sustained Attention Following Consumption of a Natural Citicoline-Caffeine Beverage - PMC: Int J Food Sci Nutr 

  • Findings: 60 healthy adults taking 250 mg of citicoline with caffeine resulted in significant improvements in measures of sustained attention and working memory. Participants also underwent EEG brain scans, and those receiving citicoline and caffeine showed higher activity in pre-frontal and frontal cortex areas, which have been associated with working memory and sustained attention.

Study: McGlade E, Locatelli A, Hardy J et al. (2012) Improved Attentional Performance Following Citicoline Administration in Healthy Adult Women. Food and Nutrition Sciences 3, 769-773. 

  • Findings: 28 days of 250 mg/day or 500 mg/day citicoline supplementation lead to increased measures of attention, with 500 mg/day showing significantly better ability to produce correct responses on the CPT-II (Continuous Performance Test) compared to placebo.

Study: Almeria M, Alvarez I, Molina-Seguin J et al. (2023) Citicoline May Prevent Cognitive Decline in Patients with Cerebrovascular Disease. Clinical interventions in aging 18.

  • Findings: 1 gram/day citicoline for 12 months showed improvements in global language domain, naming, attention, visuospatial abilities, delayed memory, global cognition and cognitive flexibility in 81 patients with mild cognitive impairment and subjective cognitive complaints.

Study (Systematic Review): Jasielski P, Piędel F, Piwek M, Rocka A, Petit V, Rejdak K (2020). Application of Citicoline in Neurological Disorders: A Systematic Review - PMC. Nutrients. PMID: 33053828; 

  • Findings: Citicoline has been shown to be useful in inhibiting disease progression of dementia, and according to the results of some studies, reversing adverse changes associated with dementia.

Study: Alvarez XA, Mouzo R, Pichel V et al. (1999) Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. Methods and findings in experimental and clinical pharmacology.

  • Findings: 30 patients with mild to moderate Alzheimer's disease taking 1000 mg/day citicoline for 12 weeks showed improved cognitive performance and increased cerebral blood flow velocities in comparison with placebo. 

Study: Winslow W, Judd JM, Tallino S, Serrano GE, Beach TG, Roust LR, De Filippis E, Brown B, Katsanos C, Velazquez R. (2025) Reduced Blood Choline in Obesity Is Associated with Metabolic and Alzheimer's Biomarkers - PubMed  Aging Dis. PMID: 41296930.

  • Findings: Low levels of choline were linked to increased inflammation and Alzheimer's biomarkers in young adults with obesity.

Study: Caamaño J, Gómez MJ, Franco A et al. (1994) Effects of CDP-choline on cognition and cerebral hemodynamics in patients with Alzheimer's disease. Methods and findings in experimental and clinical pharmacology.

  • Findings:  20 patients with Alzheimer's given 1000 mg/day citicoline for 4 weeks showed significant improvements on cognitive tests and increased cerebral blood flow vs placebo.

Study: Cacabelos R, Caamaño J, Gómez MJ et al. (1996) Therapeutic effects of CDP-choline in Alzheimer's disease. Cognition, brain mapping, cerebrovascular hemodynamics, and immune factors. Annals of the New York Academy of Sciences.

  • Findings: Alzheimer's patients taking 1000 mg/day of citicoline for 1 month showed improvements in immune factors, and increased plasma TNF (tumor necrosis factor), a protein that helps fight inflammation and cancer. 

Study: Gareri P, Castagna A, Cotroneo AM et al. (2017) The Citicholinage Study: Citicoline Plus Cholinesterase Inhibitors in Aged Patients Affected with Alzheimer's Disease Study. Journal of Alzheimer's disease.

  • Findings: 251 patients with Alzheimer’s disease being treated with 1000 mg/day citicoline plus an AChEI (Acetylcholinesterase inhibitor, a type of drug given to Alzheimer's patients) for 9 months produced better outcomes on some cognitive and functional measures than cholinesterase inhibitors alone, suggesting that taking citicoline with standard Alzheimer's treatment drugs may have an additive or synergistic benefit. 

Study (Systematic Review): Fioravanti M, Yanagi M (2004). Cytidinediphosphocholine (CDP choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. The Cochrane database of systematic reviews.

  • Findings:  13 studies were reviewed with authors concluding that there is evidence that CDP-Choline has a positive effect on memory and behavior, at least in the short/medium term, in those suffering with chronic cerebral disorders.

Study: Dávalos A, Castillo J, Alvarez-Sabín J, Secades JJ, Mercadal J, López S, Cobo E, Warach S, Sherman D, Clark WM, Lozano R. Stroke. (2002) Oral Citicoline in Acute Ischemic Stroke: An Individual Patient Data Pooling Analysis of Clinical Trials PMID: 12468781

  • Findings: Meta-analysis of studies, showing 12 weeks of citicoline supplementation given within 24 hours of moderate to severe stroke led to significantly increased probability to recover activities of daily living by 29% and the probability to recover functional capacity by 42%. Global recovery was seen with 25.2% of people given citicoline compared with 20.2% of patients who received placebo

Study: Saver JL (2008) Citicoline: update on a promising and widely available agent for neuroprotection and neurorepair - PubMed. Rev Neurol Dis. Fall, PMID: 19122569. 

  • Findings: Meta-analysis of 10 clinical trials with 2279 patients suggests patients receiving citicoline had substantially reduced frequencies of death and disability following a stroke.

Study: Killgore WD, Ross AJ, Kamiya T, Kawada Y, Renshaw PF, Yurgelun-Todd DA (2010) Citicoline Affects Appetite and Cortico-Limbic Responses to Images of High Calorie Foods - PMC  Int J Eat Disord. PMID: 19260039; 

  • Findings: 2000 mg of citicoline per day for 6 weeks led to a significant reduction in appetite ratings. Participants also underwent fMRI brain scans while viewing high calorie food items. Increased activity within the amygdala, insula, and lateral orbitofrontal cortex was seen, which correlated with declines in appetite ratings.

Studies: (Systematic Reviews):

1. Que DS, Jamora RDG (2021) Citicoline as Adjuvant Therapy in Parkinson's Disease: A Systematic Review. Clin Ther. 2021 Jan;43(1):e19-e31. doi: 10.1016/j.clinthera.2020.11.009. Epub 2020 Dec 3. PMID: 33279231.

2. Secades JJ, Lorenzo JL (2006) Citicoline: pharmacological and clinical review, 2006 update - PubMed Methods Find Exp Clin Pharmacol. PMID: 17171187.

3. Eberhardt R, Birbamer G, Gerstenbrand F, Rainer E, Traegner H. (1990) Citicoline in the treatment of Parkinson's disease - PubMed. Clin Ther. 1990 Nov-Dec;12(6):489-95. PMID: 2289218

  • Findings: Multiple studies were reviewed (2 crossover, 3 randomized controlled, and 2 open prospective studies). Patients with Parkinson's Disease who were taking citicoline daily had significant improvement in rigidity, akinesia (loss of ability to use muscles voluntarily), tremor, handwriting, walking and speech. Taking citicoline also allowed people to take up to 50% less levodopa (current drug used for Parkinson’s) and reach the same benefit. Significant improvement in cognitive status evaluation was also noted with citicoline adjunctive therapy.

Study: Martí Massó JF, Urtasun M (1991) Citicoline in the treatment of Parkinson's disease - PubMed Clin Ther. Mar-Apr;13(2):239-42. PMID: 1863939.

  • Findings: 20 patients received 1,000 mg of citicoline intramuscularly daily for 15 days, and then 500 mg daily for 15 days. After 30 days of treatment, patients saw improvements on a scale that tested depression/suicidality, as well as improvements in rigidity, 10 meter walk times, turn over times, and handwriting test scores. No side effects were reported.




Phosphatidylserine

Study: Hellhammer J, Vogt D, Franz N, Freitas U, Rutenberg D.(2014) A soy-based phosphatidylserine/ phosphatidic acid complex (PAS) normalizes the stress reactivity of hypothalamus-pituitary-adrenal-axis in chronically stressed male subjects: a randomized, placebo-controlled study - PMC. Lipids Health Dis. 25081826

  • Findings: 75 healthy male stratified by chronic stress level, were given placebo, 200mg or 400mg of phosphatidylserine/phosphatidic acid for 6 weeks.  Compared to placebo, supplementation with a daily dose of 400 mg PAS was effective in normalizing the ACTH (hormone that stimulates the adrenal glands to produce cortisol), salivary and serum cortisol responses to an acute stress test in chronically high stressed subjects.

Study: Benton, D., Donohoe, R. T., Sillance, B., & Nabb, S. (2001).The Influence of Phosphatidylserine Supplementation on Mood and Heart Rate when Faced with an Acute Stressor  Nutritional Neuroscience.

  • Findings: 300 mg/day phosphatidylserine supplementation for 4 weeks was associated with improvements in mood and reductions in stress in young healthy adults.

Study: Monteleone P, et al. (1992) Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men.European Journal of Clinical Pharmacology

  • Findings: 9 men given Phosphatidylserine 800 mg/d for 10 days had significantly blunted levels of ACTH and cortisol responses (stress hormones) to physical exercise without affecting the rise in plasma growth hormone and prolactin. This suggests that oral administration of phosphatidylserine may counteract stress-induced activation of the HPAA (hypothalamic-pituitary-adrenal axis).

Study: Starks MA, Starks SL, Kingsley M, Purpura M, Jäger R. (2008)  The effects of phosphatidylserine on endocrine response to moderate intensity exercise - PubMed. J Int Soc Sports Nutr. PMID: 18662395.

  • Findings: 10 healthy male subjects were given 600 mg/day phosphatidylserine or placebo for 10 days. Blood samples were taken at rest, after a 15 minute moderate intensity exercise protocol. Subjects taking PS showed reductions in cortisol levels and an increase in testosterone to cortisol ratio when compared to placebo. The findings suggest that PS is an effective supplement for combating exercise-induced stress and preventing the physiological deterioration that can accompany too much exercise. 

Study: Vakhapova V, Cohen T, Richter Y, Herzog Y, Korczyn AD. (2010) Phosphatidylserine containing omega-3 fatty acids may improve memory abilities in non-demented elderly with memory complaints: a double-blind placebo-controlled trial - PubMed. Dement Geriatr Cogn Disord. PMID: 20523044.

  • Findings: 131 participants with memory complaints were given phosphatidylserine + DHA (Omega 3 fatty acids) or placebo for 15 weeks. Significant improvements in verbal immediate recall seen in the PS-DHA group compared to the placebo group. Follow up analysis showed that a subset of participants with relatively good cognitive performance at baseline who had taken PS+DHA had significant improvements in immediate and delayed verbal recall, learning abilities, and time taken to copy a complex figure. 

Study: Crook TH, Tinklenberg J, Yesavage J, Petrie W, Nunzi MG, Massari DC. (1991). Effects of phosphatidylserine in age-associated memory impairment - PubMed PMID: 2027477.

  • Findings: 149 patients meeting criteria for age-associated memory impairment (AAMI) were given 100 mg/day phosphatidylserine for 12 weeks.  Patients treated with PS improved relative to those treated with placebo on performance tests related to learning and memory tasks of daily life


Study: Richter Y, Herzog Y, Lifshitz Y, Hayun R, Zchut S (2013) The effect of soybean-derived phosphatidylserine on cognitive performance in elderly with subjective memory complaints: a pilot study. Clin Interv Aging doi: 10.2147

  • Findings: 30 elderly volunteers with memory complaints (age range 50–90 years)  were given 300 mg/day phosphatidylserine for 12 weeks.. Improvements were seen in memory recognition, memory recall, executive functions and mental flexibility. Total learning and immediate recall also improved significantly. Interestingly, phosphatidylserine supplementation also reduced blood pressure slightly.

Study: Hirayama S., Terasawa K., Rabeler R., Hirayama T., Inoue T., Tatsumi Y., et al. (2014) The effect of phosphatidylserine administration on memory and symptoms of attention‐deficit hyperactivity disorder: a randomised, double‐blind, placebo‐controlled clinical trial. J. Hum. Nutr. Diet

  • Findings: 36 children aged 4–14 years, who had not previously received any drug treatment related to ADHD, received placebo or 200 mg/day phosphatidylserine for 8 weeks. Phosphatidylserine supplementation resulted in significant improvements in ADHD symptoms as well as improvements in short-term auditory memory, inattention and impulsivity. PS was well-tolerated and showed no adverse effects.

Study: Ma X, Li X, Wang W, Zhang M, Yang B, Miao Z. (2022) Phosphatidylserine, inflammation, and central nervous system diseases - PMC  Front Aging Neuroscience.  PMID: 35992593

  • Findings: “Phosphatidylserine is an important component in the cell membrane, especially with high proportion in the brain and has critical multiple functions involving in cellular signal transduction, cell death and survival, and inflammation. Oral phosphatidylserine benefits patients with different CNS diseases including Parkinson's disease, Alzheimer's disease, major depressive disorder and ADHD. In addition, clinical studies also showed that PS had no side effects and was well tolerated”


Study (Systematic Review/Meta-analysis): Bruton A, Nauman J, Hanes D, Gard M, Senders A (2021) Phosphatidylserine for the Treatment of Pediatric Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis - PMC  J Altern Complement Med. PMID: 33539192;

  • Findings: Four studies analyzing 200-300 mg/day of phosphatidylserine supplementation showed significant improvements on symptoms of inattentions when compared to placebo. 

Study: Manor I, Magen A, Keidar D, Rosen S, Tasker H, Cohen T, Richter Y, Zaaroor-Regev D, Manor Y, Weizman A (2012)  The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension - PubMed  PMID: 21807480 

  • Findings: 200 children with ADHD were given a supplement containing phosphatidylserine and Omega-3 fatty acids for 15 weeks vs placebo, followed by a 15 week open-label extension (150 children continue to take the supplement). Supplementation with phosphatidylserine and Omega-3’s lead to a significant reduction of ADHD symptoms on 3 different scales.

Study: Komori T.(2015) The Effects of Phosphatidylserine and Omega-3 Fatty Acid-Containing Supplement on Late Life Depression - PMC . Ment Illn. PMID: 26266022 

  • Findings:  18 elderly subjects were given a supplement containing PS 100 mg, DHA 119 mg and EPA 70 mg , 3 times a day for 12 weeks The effects of the supplement were assessed using the 17-item Hamilton depression scale (HAM-D17) and the basal levels and circadian rhythm of salivary cortisol.  Significant improvements were seen on symptoms of depression as well as a regulation of cortisol (stress hormone) levels.

Study: Moré, M.I., Freitas, U. & Rutenberg, D (2104)  Positive Effects of Soy Lecithin-Derived Phosphatidylserine plus Phosphatidic Acid on Memory, Cognition, Daily Functioning, and Mood in Elderly Patients with Alzheimer’s Disease and Dementia | Advances in Therapy. Adv Ther

  • Findings:  Participants with and without Alzheimer's disease were given 300 mg/day of phosphatidylserine + 240 mg/day phosphatidic acid for 3 months. In the elderly, PS+PA significantly improved memory and prevented “winter blues” in a pre–post comparison. In the patients with Alzheimer's disease, taking PS+PA showed no changes in daily functionality, but there was a decline in daily function in the placebo group. Patients taking PS+PS showed a 49% improvement in general condition, compared to 26.3% under placebo. 

Blueberry Anthocyanin Extract

Study: Barfoot KL, May G, Lamport DJ, Ricketts J, Riddell PM, Williams CM (2019). The effects of acute wild blueberry supplementation on the cognition of 7–10-year-old schoolchildren - PMC. Eur J Nutr. 

  • Findings: 54 healthy children consumed 200 ml of a wild blueberry drink (253 mg anthocyanins) or a placebo. Tests of  memory, attention and reading efficiency were done at baseline and 2 hours after consumption. Children who drank the wild blueberry beverage were found to have significantly improved memory and attentional aspects of executive function.

Study: McNamara RK, Kalt W, Shidler MD, McDonald J, Summer SS, Stein AL, Stover AN, Krikorian R. (2018) Cognitive Response to Fish Oil, Blueberry, and Combined Supplementation in Older Adults With Subjective Cognitive Impairment - PubMed. Neurobiol Aging. PMID: 29458842 

  • Findings: 94 people were given blueberry powder (269 mg anthocyanins), an Omega-3 fish oil supplement (1.6 g EPA and 0.8 g DHA), or both daily for 24 weeks. The group receiving both blueberry powder and fish oil reported fewer cognitive symptoms, and the BB powder group showed improved memory discrimination indicating that supplementation improved cognition. 

Study: Krikorian, R., Skelton, M. R., Summer, S. S., Shidler, M. D., & Sullivan, P. G. (2022).  Blueberry Supplementation in Midlife for Dementia Risk Reduction. Nutrients.

  • Findings: 33 total participants with insulin-resistance were given a placebo powder or the equivalent of 0.5 cups of whole-fruit equivalent blueberry extract powder daily for 12 weeks. Improvements were seen in mental recall and executive abilities. The findings suggest that supplementation has potential for protection against future neurocognitive decline in vulnerable individuals.

Study: Miller MG, Hamilton DA, Joseph JA, Shukitt-Hale B (2018)  Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial - PubMed. Eur J Nutr. PMID: 28283823. 

  • Findings:  13 men and 24 women, between the ages of 60 and 75 years, consumed either freeze-dried blueberry (24 g/day, equivalent to 1 cup of fresh blueberries) or a blueberry placebo for 90 days. Participants given the blueberry extract showed significantly fewer repetition errors in a verbal learning test, and reduced “switch cost” (time and mental effort lost) on a task-switching test across study visits, relative to placebo.

Study: Barfoot KL, Istas G, Feliciano RP, Lamport DJ, Riddell P, Rodriguez-Mateos A, Williams CM.(2021) Effects of daily consumption of wild blueberry on cognition and urinary metabolites in school-aged children: a pilot study - PMC  Eur J Nutr. 

  • Findings: 15 healthy children were given 13.3 grams of a wild blueberry beverage (equivalent to 253 mg anthocyanins) vs a placebo for 4 weeks . Significant improvements in cognition were observed in children consuming the wild blueberry beverage, specifically on trials requiring high cognitive demand, vs placebo.

Study: Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqvist-Tymchuk MR, Shukitt-Hale B, Joseph JA. (2010) Blueberry supplementation improves memory in older adults - PubMed J Agric Food Chem. PMID: 20047325 

  • Findings: 9 subjects with early memory complaints were  given a daily drink of wild blueberry juice for 12 weeks. Results showed improved paired associate learning and word list recall. In addition, there were trends suggesting reduced depressive symptoms and lower glucose levels 

Study (Systematic Review): Travica N, D'Cunha NM, Naumovski N, Kent K, Mellor DD, Firth J, Georgousopoulou EN, Dean OM, Loughman A, Jacka F, Marx W .(2020) The effect of blueberry interventions on cognitive performance and mood: A systematic review of randomized controlled trials - PubMed. Brain Behav Immun. PMID: 30999017.

  • Findings: 11 studies were reviewed looking at the evidence of blueberries and blueberry concentrates on cognitive performance and mood. 8 studies reported blueberry consumption or supplementation at various doses and time lengths improved measures of cognitive performance, particularly short- and long-term memory and spatial memory. 1 study reported significant improvements in mood from blueberry products. 

Study: Whyte AR, Cheng N, Fromentin E, Williams CM.(2018) A Randomized, Double-Blinded, Placebo-Controlled Study to Compare the Safety and Efficacy of Low Dose Enhanced Wild Blueberry Powder and Wild Blueberry Extract (ThinkBlue™) in Maintenance of Episodic and Working Memory in Older Adults - PMC Nutrients. PMID: 29882843; 

  • Findings: 122 people aged 65-80 were given 100 mg/day of purified wild blueberry anthocyanin extract, 500 mg/1000 mg/day wild blueberry powder or placebo for 6 months. Those given 100mg/day wild blueberry anthocyanin extract showed better episodic memory performance and improved cardiovascular function (lower systolic blood pressure) vs placebo over 6 months.

Study: Whyte AR, Williams CM (2015) Effects of a single dose of a flavonoid-rich blueberry drink on memory in 8 to 10 y old children - PubMed . Nutrition.. PMID: 25701345.

  • Findings: 14 children aged 8-10 were given an anthocyanin rich blueberry drink or placebo, and performed a series of cognitive tests 2 hours after consumption. Improvements were seen on memory tests in those given the blueberry drink.

Study (Systematic Review): Ellis LR, Boesch C, Dye L. (2024).  Effects of Anthocyanins on Cognition and Vascular Function: A Systematic Review - PubMed . Mol Nutr Food Res. PMID: 38961529. 

  • Findings: Multiple studies have shown anthocyanins have positive effects on verbal and working memory,  supported by studies using functional magnetic resonance imaging to demonstrate increased blood flow in brain regions related to these cognitive domains.

Study: Bowtell JL, Aboo-Bakkar Z, Conway ME, Adlam AR, Fulford J. (2017)  Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation - PubMed Appl Physiol Nutr Metab. PMID: 28249119. 

  • Findings: 26 healthy people aged 65-77 were given a blueberry concentrate supplement (~387 mg anthocyanidins) or placebo, daily for 12 weeks. A series of cognitive tests were performed while undergoing fMRI brains, and blood biomarkers of inflammation and oxidative stress were also measured. People given the blueberry concentrate showed significant increases in brain activity in multiple areas, as well as improvements in working memory vs placebo.

Study: Panchal SK, Brown L. (2022) Potential Benefits of Anthocyanins in Chronic Disorders of the Central Nervous System - PMC. Molecules. PMID: 36615279 

  • Findings: Anthocyanins work to decrease oxidative stress and inflammation and influence changes in the gut microbiota. The mechanisms of action of anthocyanins infer that anthocyanins could be beneficial for symptoms of central nervous system disorders such as ADHD, Autism Spectrum Disorder, depression and Alzheimer’s disease.

Study: Ebenezer PJ, Wilson CB, Wilson LD, Nair AR, J F. (2016) .The Anti-Inflammatory Effects of Blueberries in an Animal Model of Post-Traumatic Stress Disorder (PTSD) - PubMed  PLoS One. PMID: 27603014.

  • Findings: Rats were fed either a blueberry enriched (2%) diet or a control diet. They were then exposed to cats to simulate traumatic conditions. The rats were also subjected to psychosocial stress by constant daily changes of their cage partners. Rats who received the blueberry enriched diet had lower levels of norepinephrine (fight or flight hormone) and higher levels of serotonin (low levels of serotonin have been linked to anxiety) when compared to the placebo diet. Decreased anxiety and lower levels of free radicals and inflammation markers were also seen in the blueberry diet group.

Study: Serra D, Henriques JF, Sousa FJ, Laranjo M, Resende R, Ferreira-Marques M, de Freitas V, Silva G, Peça J, Dinis TCP, Almeida LM. (2022) Attenuation of Autism-like Behaviors by an Anthocyanin-Rich Extract from Portuguese Blueberries via Microbiota-Gut-Brain Axis Modulation in a Valproic Acid Mouse Model - PubMed. Int J Mol Sci.

  • Findings: Anthocyanin rich blueberry extract alleviated autism-like behaviors in mice subjects, while also decreasing both neuroinflammation and gut inflammation, modulating the gut microbiota composition, increasing serotonin levels in the cerebral prefrontal cortex and gut, and reducing the synaptic dysfunction verified in autistic mice. 

Study (Review): Tran PHL, Tran TTD.(2021) Blueberry Supplementation in Neuronal Health and Protective Technologies for Efficient Delivery of Blueberry Anthocyanins - PMC Biomolecules. PMID: 33466731

  • Findings: Blueberries and their constituent anthocyanins are beneficial in the treatment of age-related diseases, as they have been reported to alleviate behavioral deficits in ageing animals consuming a high-fat diet. Studies have found that the regular intake of polyphenol-rich fruit such as blueberries can delay the onset of brain ageing and neurodegenerative disorders due to their strong antioxidative and anti-inflammatory properties.

Study: Panchal, S. K., John, O. D., Mathai, M. L., & Brown, L. (2022).  Anthocyanins in Chronic Diseases: The Power of Purple  Nutrients, https://doi.org/10.3390/nu14102161

  • Findings: Anthocyanins mediate a range of pharmacological effects, including benefits to gut microbiota, decreasing oxidative stress, reducing inflammation and neuroinflammation, and increasing neuropeptide IGG-1 and cGP.

Study: Krishna, G., Ying, Z., & Gomez-Pinilla, F. (2019).Brain Plasticity and Behavior after Traumatic Brain Injury in Rats Molecular. Nutrition & Food Research  

  • Findings: Rats who recently had a traumatic brain injury (TBI) were maintained on a diet supplemented with blueberry extract for 2 weeks. BB supplementation mitigated a loss of spatial learning and memory performance after TBI, and reduced the effects of TBI on anxiety-like behavior. These effects may be achieved by the blueberry extract modulating important brain proteins, reducing oxidative stress, and increasing brain-derived neurotrophic factor (BDNF). 

Study: Rendeiro C, Vauzour D, Rattray M, Waffo-Téguo P, Mérillon JM, Butler LT, Williams CM, Spencer JP (2013). Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor - PubMed . PLoS One. PMID: 23723987

  • Findings: Supplementation with pure anthocyanins or pure flavanols for 6 weeks, at levels similar to that found in blueberries,  resulted in an enhancement of spatial memory in 18 month old rats. This was paralleled by increases in hippocampal brain-derived neurotrophic factor (BDNF), suggesting a direct mechanism for the enhancement of memory. 

Study: Fang Z, Luo Y, Ma C, Dong L, Chen F. (2022)  Blueberry Anthocyanins Extract Attenuates Acrylamide-Induced Oxidative Stress and Neuroinflammation in Rats - PubMed Oxid Med Cell Longev. PMID: 35651724.

  • Findings: Rats were given a blueberry anthocyanin extract for 7 days followed by the introduction of acrylamide, a neurotoxin that creates oxidative stress and neuroinflammation. Rats given blueberry anthocyanins had significant decreases in compounds related to oxidative stress and neuroinflammation, indicating a protective effect on neurons and synapses. Blueberry anthocyanins also relieved the accumulation of amyloid beta, a peptide strongly linked to Alzheimer's. 

Study: Çoban J, Doğan-Ekici I, Aydın AF, Betül-Kalaz E, Doğru-Abbasoğlu S, Uysal M. (2015)   Blueberry treatment decreased D-galactose-induced oxidative stress and brain damage in rats - PubMed. Metab Brain Dis 

  • Findings: Rats given an oxidative stress inducing sugar were also given a diet high in blueberries for 2 months. Those who received the blueberries saw reduced acetylcholinesterase (AChE) activity and elevated glutathione (an important antioxidant) levels. This suggests that blueberries and its constituent anthocyanins have benefits for reducing oxidative stress and may improve acetylcholine transmission.

Study: Williams CM, El Mohsen MA, Vauzour D, Rendeiro C, Butler LT, Ellis JA, Whiteman M, Spencer JP (2008). Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels - ScienceDirect Free Radic Biol Med. 

  • Findings: Animals given a diet high in blueberries for 12 weeks showed improvements in spatial memory tasks. Increases in both pro- and mature levels of brain-derived neurotrophic factor (BDNF) were also seen in the hippocampus.