Dietary supplements in neurological diseases and brain aging


Neurological diseases
Neurodegenerative diseases
Dietary supplements
Mediterranean diet
Ayurvedic herbs


A healthy diet shapes a healthy mind. Diet quality has a strong association with brain health. Diet influences the onset and consequences of neurological diseases, and dietary factors may influence mental health at individual and population level. The link between unhealthy diet, impaired cognitive function and neurodegenerative diseases indicates that adopting a healthy diet would ultimately afford prevention and management of neurological diseases and brain aging. Neurodegenerative diseases are of multifactorial origin and result in progressive loss of neuronal function in the brain, leading to cognitive impairment and motoneuron disorders. The so-called Mediterranean diet (MedDiet) with its healthy ingredients rich in antioxidant, anti-inflammatory, immune, neuroprotective, antidepressant, antistress and senolytic activity plays an essential role in the prevention and management of neurological diseases and inhibits cognitive decline in neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases. The MedDiet also modulates the gut-brain axis by promoting a diversity of gut microbiota. In view of the importance of diet in neurological diseases management, this review focuses on the dietary components, natural compounds and medicinal plants that have proven beneficial in neurological diseases and for brain health. Among them, polyphenols, omega-3 fatty acids, B vitamins and several ayurvedic herbs have promising beneficial effects.


[1] Bianchi VE, Herrera PF, Laura R. Effect of nutrition on neurodegenerative diseases. A systematic review. Nutr Neurosci 2021;24:810-34. 5X.2019.1681088
[2] Caplliure-Llopis J, Peralta-Chamba T, Carrera-Juliá S, Cuerda-Ballester M, Drehmer-Rieger E, López-Rodriguez MM, de la Rubia Ortí JE. Therapeutic alternative of the ketogenic Mediterranean diet to improve mitochondrial activity in Amyotrophic Lateral Sclerosis (ALS): A Comprehensive Review. Food Sci Nutr 2019;8:23-35.
[3] Esposito E, Rotilio D, Di Matteo V, Di Giulio C, Cacchio M, Algeri S. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging 2002;23:719-35.
[4] Lardenoije R, van den Hove DLA, Havermans M, van Casteren A, Le KX, Palmour R, Lemere CA, Rutten BPF. Age-related epigenetic changes in hippocampal subregions of four animal models of Alzheimer’s disease. Mol Cell Neurosci 2018;86:1-15.
[5] Chiurazzi P, Kiani AK, Miertus J, Paolacci S, Barati S, Manara E, Stuppia L, Gurrieri F, Bertelli M. Genetic analysis of intellectual disability and autism. Acta Biomed 2020;91:e2020003.
[6] Allison J, Kaliszewska A, Uceda S, Reiriz M, Arias N. Targeting DNA Methylation in the Adult Brain through Diet. Nutrients 2021;13:3979.
[7] Berti V, Walters M, Sterling J, Quinn CG, Logue M, Andrews R, Matthews DC, Osorio RS, Pupi A, Vallabhajosula S, Isaacson RS, de Leon MJ, Mosconi L. Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults. Neurology 2018;90:e1789-e1798.
[8] Scarmeas N, Stern Y, Mayeux R, Manly JJ, Schupf N, Luchsinger JA. Mediterranean diet and mild cognitive impairment. Arch Neurol 2009;66:216-25.
[9] Anastasiou CA, Yannakoulia M, Kosmidis MH, Dardiotis E, Hadjigeorgiou GM, Sakka P, Arampatzi X, Bougea A, Labropoulos I, Scarmeas N. Mediterranean diet and cognitive health: Initial results from the Hellenic Longitudinal Investigation of Ageing and Diet. PLoS One 2017;12:e0182048.
[10] Mosconi L, Murray J, Tsui WH, Li Y, Davies M, Williams S, Pirraglia E, Spector N, Osorio RS, Glodzik L, McHugh P, de Leon MJ. Mediterranean Diet and Magnetic Resonance Imaging-Assessed Brain Atrophy in Cognitively Normal Individuals at Risk for Alzheimer’s Disease. J Prev Alzheimers Dis 2014;1:23-32.
[11] Marder K, Gu Y, Eberly S, Tanner CM, Scarmeas N, Oakes D, Shoulson I; Huntington Study Group PHAROS Investigators. Relationship of Mediterranean diet and caloric intake to phenoconversion in Huntington disease. JAMA Neurol 2013;70:1382-8.
[12] Maraki MI, Yannakoulia M, Stamelou M, Stefanis L, Xiromerisiou G, Kosmidis MH, Dardiotis E, Hadjigeorgiou GM, Sakka P, Anastasiou CA, Simopoulou E, Scarmeas N. Mediterranean diet adherence is related to reduced probability of prodromal Parkinson’s disease. Mov Disord 2019;34:48-57.
[13] Nieves JW, Gennings C, Factor-Litvak P, Hupf J, Singleton J, Sharf V, Oskarsson B, Fernandes Filho JA, Sorenson EJ, D’Amico E, Goetz R, Mitsumoto H; Amyotrophic Lateral Sclerosis Multicenter Cohort Study of Oxidative Stress (ALS COSMOS) Study Group. Association Between Dietary Intake and Function in Amyotrophic Lateral Sclerosis. JAMA Neurol 2016;73:1425-32.
[14] Zhang WT, Zhang GX, Zhao RZ, Gao SS, G. Zhao, Izquierdo G. Eating habits of patients with multiple sclerosis in three different countries: China, Spain and Cuba. Neurology Perspectives 2021;1:170-7.
[15] Kouka P, Priftis A, Stagos D, Angelis A, Stathopoulos P, Xinos N, Skaltsounis AL, Mamoulakis C, Tsatsakis AM, Spandidos DA, Kouretas D. Assessment of the antioxidant activity of an olive oil total polyphenolic fraction and hydroxytyrosol from a Greek Olea europea variety in endothelial cells and myoblasts. Int J Mol Med 2017;40:703-12.
[16] Kiani AK, Miggiano G, Aquilanti B, Velluti V, Matera G, Gagliardi L, Bertelli M. Food supplements based on palmitoylethanolamide plus hydroxytyrosol from olive tree or Bacopa monnieri extracts for neurological diseases. Acta Biomed 2020;91:2020007. v91i13-S.10582
[17] Kalaiselvan I, Samuthirapandi M, Govindaraju A, Sheeja Malar D, Kasi PD. Olive oil and its phenolic compounds (hydroxytyrosol and tyrosol) ameliorated TCDD-induced heptotoxicity in rats via inhibition of oxidative stress and apoptosis. Pharm Biol 2016;54:338-46. 13880209.2015.1042980
[18] Grossi C, Rigacci S, Ambrosini S, Ed Dami T, Luccarini I, Traini C, Failli P, Berti A, Casamenti F, Stefani M. The polyphenol oleuropein aglycone protects TgCRND8 mice against Aß plaque pathology. PLoS One 2013;8:e71702.
[19] Zoccolella S, Beghi E, Palagano G, Fraddosio A, Guerra V, Samarelli V, Lepore V, Simone IL, Lamberti P, Serlenga L, Logroscino G. Analysis of survival and prognostic factors in amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry 2008;79:33-7.
[20] Mancuso C, Santangelo R. Ferulic acid: pharmacological and toxicological aspects. Food Chem Toxicol 2014;65:185-95.
[21] Debbabi M, Zarrouk A, Bezine M, Meddeb W, Nury T, Badreddine A, Karym EM, Sghaier R, Bretillon L, Guyot S, Samadi M, Cherkaoui-Malki M, Nasser B, Mejri M, Ben-Hammou S, Hammami M, Lizard G. Comparison of the effects of major fatty acids present in the Mediterranean diet (oleic acid, docosahexaenoic acid) and in hydrogenated oils (elaidic acid) on 7-ketocholesterol-induced oxiapoptophagy in microglial BV-2 cells. Chem Phys Lipids 2017;207:151-70.
[22] Rogers PJ. A healthy body, a healthy mind: long-term impact of diet on mood and cognitive function. Proc Nutr Soc 2001;60:135-43.
[23] Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, Marangell LB. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry 1999;56:407-12.
[24] Hakkarainen R, Partonen T, Haukka J, Virtamo J, Albanes D, Lönnqvist J. Food and nutrient intake in relation to mental wellbeing. Nutr J 2004;3:14.
[25] Parletta N, Zarnowiecki D, Cho J, Wilson A, Bogomolova S, Villani A, Itsiopoulos C, Niyonsenga T, Blunden S, Meyer B, Segal L, Baune BT, O’Dea K. A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED). Nutr Neurosci 2019;22:474-87.
[26] Jacka FN, O’Neil A, Opie R, Itsiopoulos C, Cotton S, Mohebbi M, Castle D, Dash S, Mihalopoulos C, Chatterton ML, Brazionis L, Dean OM, Hodge AM, Berk M. A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Med 2017;15:23.
[27] Bayes J, Schloss J, Sibbritt D. Effects of Polyphenols in a Mediterranean Diet on Symptoms of Depression: A Systematic Literature Review. Adv Nutr 2020;11:602-15.
[28] García-Toro M, Vicens-Pons E, Gili M, Roca M, Serrano-Ripoll MJ, Vives M, Leiva A, Yáñez AM, Bennasar-Veny M, Oliván-Blázquez B. Obesity, metabolic syndrome and Mediterranean diet: Impact on depression outcome. J Affect Disord 2016;194:105-8.
[29] Vicinanza R, Bersani FS, D’Ottavio E, Murphy M, Bernardini S, Crisciotti F, Frizza A, Mazza V, Biondi M, Troisi G, Cacciafesta M. Adherence to Mediterranean diet moderates the association between multimorbidity and depressive symptoms in older adults. Arch Gerontol Geriatr 2020;88:104022.
[30] Sánchez-Villegas A, Cabrera-Suárez B, Molero P, González-Pinto A, Chiclana-Actis C, Cabrera C, Lahortiga-Ramos F, Florido-Rodríguez M, Vega-Pérez P, Vega-Pérez R, Pla J, Calviño-Cabada MJ, Ortuño F, Navarro S, Almeida Y, Hernández-Fleta JL. Preventing the recurrence of depression with a Mediterranean diet supplemented with extra-virgin olive oil. The PREDI-DEP trial: study protocol. BMC Psychiatry 2019;19:63.
[31] Jacka FN, Pasco JA, Mykletun A, Williams LJ, Nicholson GC, Kotowicz MA, Berk M. Diet quality in bipolar disorder in a population-based sample of women. J Affect Disord 2011;129:332-7.
[32] Gesch CB, Hammond SM, Hampson SE, Eves A, Crowder MJ. Influence of supplementary vitamins, minerals and essential fatty acids on the antisocial behaviour of young adult prisoners. Randomised, placebo-controlled trial. Br J Psychiatry 2002;181:22-8.
[33] Neumeister A, Turner EH, Matthews JR, Postolache TT, Barnett RL, Rauh M, Vetticad RG, Kasper S, Rosenthal NE. Effects of tryptophan depletion vs catecholamine depletion in patients with seasonal affective disorder in remission with light therapy. Arch Gen Psychiatry 1998;55:524-30.
[34] Reynolds EH. Folic acid, ageing, depression, and dementia. BMJ 2002;324:1512-5.
[35] Botez MI, Fontaine F, Botez T, Bachevalier J. Folate-responsive neurological and mental disorders: report of 16 cases. Neuropsychological correlates of computerized transaxial tomography and radionuclide cisternography in folic acid deficiencies. Eur Neurol 1977;16:230-46.
[36] Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy elderly population. JAMA 1983;249:2917-21.
[37] Dekhuijzen PN. Antioxidant properties of N-acetylcysteine: their relevance in relation to chronic obstructive pulmonary disease. Eur Respir J 2004;23:629-36. 09031936.04.00016804
[38] Bavarsad Shahripour R, Harrigan MR, Alexandrov AV. N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities. Brain Behav 2014;4:108-22.
[39] Arakawa M, Ito Y. N-acetylcysteine and neurodegenerative diseases: basic and clinical pharmacology. Cerebellum 2007;6:308-14.
[40] Stanislaus R, Gilg AG, Singh AK, Singh I. N-acetyl-L-cysteine ameliorates the inflammatory disease process in experimental autoimmune encephalomyelitis in Lewis rats. J Autoimmune Dis 2005;2:4.
[41] Louwerse ES, Weverling GJ, Bossuyt PM, Meyjes FE, de Jong JM. Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis. Arch Neurol 1995;52:559-64.
[42] Schapira AH, Mann VM, Cooper JM, Dexter D, Daniel SE, Jenner P, Clark JB, Marsden CD. Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson’s disease. J Neurochem 1990;55:2142-5.
[43] Tchantchou F, Graves M, Rogers E, Ortiz D, Shea TB. N-acteyl cysteine alleviates oxidative damage to central nervous system of ApoE-deficient mice following folate and vitamin E-deficiency. J Alzheimers Dis 2005;7:135-8.
[44] Dawson TM, Dawson VL. Protection of the brain from ischemia. Cerebrovasc Dis 1997;7:349-52.
[45] Khrameeva E, Kurochkin I, Bozek K, Giavalisco P, Khaitovich P. Lipidome Evolution in Mammalian Tissues. Mol Biol Evol 2018;35:1947-57.
[46] Choi J, Yin T, Shinozaki K, Lampe JW, Stevens JF, Becker LB, Kim J. Comprehensive analysis of phospholipids in the brain, heart, kidney, and liver: brain phospholipids are least enriched with polyunsaturated fatty acids. Mol Cell Biochem 2018;442:187-201.
[47] Oliveira TG, Chan RB, Bravo FV, Miranda A, Silva RR, Zhou B, Marques F, Pinto V, Cerqueira JJ, Di Paolo G, Sousa N. The impact of chronic stress on the rat brain lipidome. Mol Psychiatry 2016;21:80-8.
[48] Schverer M, O’Mahony SM, O’Riordan KJ, Donoso F, Roy BL, Stanton C, Dinan TG, Schellekens H, Cryan JF. Dietary phospholipids: Role in cognitive processes across the lifespan. Neurosci Biobehav Rev 2020;111:183-93.
[49] Liu H, Radlowski EC, Conrad MS, Li Y, Dilger RN, Johnson RW. Early supplementation of phospholipids and gangliosides affects brain and cognitive development in neonatal piglets. J Nutr 2014;144:1903-9.
[50] Hanin I, Ansell GB. Lecithin. Technological, biological, and therapeutic aspects. Boston: Spinger 1987.
[51] Mark A, McDaniel Steven F, Maier Gilles O. Einstein. “Brain-specific” nutrients: a memory cure? Nutrition 2003;19:957-75.
[52] Crook TH, Tinklenberg J, Yesavage J, Petrie W, Nunzi MG, Massari DC. Effects of phosphatidylserine in age-associated memory impairment. Neurology 1991;41:644-9.
[53] Hellhammer J, Vogt D, Franz N, Freitas U, Rutenberg D. 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. Lipids Health Dis 2014;13:121.
[54] Manor I, Magen A, Keidar D, Rosen S, Tasker H, Cohen T, Richter Y, Zaaroor-Regev D, Manor Y, Weizman A. 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. Eur Psychiatry 2012;27:335-42.
[55] Murray J, Cuccia L, Ianoul A, Cheetham JJ, Johnston LJ. Imaging the selective binding of synapsin to anionic membrane domains. Chembiochem 2004;5:1489-94.
[56] Faria R, Santana MM, Aveleira CA, Simões C, Maciel E, Melo T, Santinha D, Oliveira MM, Peixoto F, Domingues P, Cavadas C, Domingues MR. Alterations in phospholipidomic profile in the brain of mouse model of depression induced by chronic unpredictable stress. Neuroscience 2014;273:1-11.
[57] Söderberg M, Edlund C, Kristensson K, Dallner G. Lipid compositions of different regions of the human brain during aging. J Neurochem 1990;54:415-23.
[58] Moré MI, Freitas U, Rutenberg D. 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. Adv Ther 2014;31:1247-62.
[59] Hirayama S, Terasawa K, Rabeler R, Hirayama T, Inoue T, Tatsumi Y, Purpura M, Jäger R. 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 2014;27:284-91.
[60] Vakhapova V, Cohen T, Richter Y, Herzog Y, Kam Y, Korczyn AD. Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study. Dement Geriatr Cogn Disord 2014;38:39-45.
[61] Vakhapova V, Cohen T, Richter Y, Herzog Y, Korczyn AD. Phosphatidylserine containing omega-3 fatty acids may improve memory abilities in non-demented elderly with memory complaints: a double-blind placebo-controlled trial. Dement Geriatr Cogn Disord 2010;29:467-74.
[62] Kennedy DO, Haskell CF, Mauri PL, Scholey AB. Acute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserine. Hum Psychopharmacol 2007;22:199-210.
[63] Baumeister J, Barthel T, Geiss KR, Weiss M. Influence of phosphatidylserine on cognitive performance and cortical activity after induced stress. Nutr Neurosci 2008;11:103-10.
[64] Jorissen BL, Brouns F, Van Boxtel MP, Riedel WJ. Safety of soy-derived phosphatidylserine in elderly people. Nutr Neurosci 2002;5:337-43.
[65] Cenacchi T, Bertoldin T, Farina C, Fiori MG, Crepaldi G. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging (Milano) 1993;5:123-33.
[66] Olsen RW, DeLorey TM. GABA and Glycine. In: Siegel GJ, Agranoff BW, Albers RW, Fisher S K, Uhler MD, eds. Basic neurochemistry: molecular, cellular and medical aspects. Sixth edition. Philadelphia: Lippincott-Raven 1999.
[67] Nuss P. Anxiety disorders and GABA neurotransmission: a disturbance of modulation. Neuropsychiatr Dis Treat 2015;11:165-75.
[68] Byun JI, Shin YY, Chung SE, Shin WC. Safety and Efficacy of Gamma-Aminobutyric Acid from Fermented Rice Germ in Patients with Insomnia Symptoms: A Randomized, Double-Blind Trial. J Clin Neurol 2018;14:291-5.
[69] Ngo DH, Vo TS. An Updated Review on Pharmaceutical Properties of Gamma-Aminobutyric Acid MoleculesM2019;24:2678.
[70] Murari G, Liang DR, Ali A, Chan F, Mulder-Heijstra M, Verhoeff NPLG, Herrmann N, Chen JJ, Mah L. Prefrontal GABA Levels Correlate with Memory in Older Adults at High Risk for Alzheimer’s Disease. Cereb Cortex Commun 2020;1:tgaa022.
[71] Okada T, Sugishita T, Murakami T, Murai H, Saikusa T, Horino T, Onoda A, Kajimoto O, Takahashi R, Takahashi T. Effect of the Defatted Rice Germ Enriched with GABA for Sleeplessness, Depression, Autonomic Disorder by Oral Administration. Nippon Shokuhin Kagaku Kogaku Kaishi 2000;47:596-603.
[72] Chuang CY, Shi YC, You HP, Lo YH, Pan TM. Antidepressant effect of GABA-rich monascus-fermented product on forced swimming rat model. J Agric Food Chem 2011;59:3027-34.
[73] Yamatsu A, Yamashita Y, Pandharipande T, Maru I, Kim M. Effect of oral γ-aminobutyric acid (GABA) administration on sleep and its absorption in humans. Food Sci Biotechnol 2016;25:547-51.
[74] Kim S, Jo K, Hong KB, Han SH, Suh HJ. GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. Pharm Biol 2019;57:65-73. 2018.1557698
[75] Abdou AM, Higashiguchi S, Horie K, Kim M, Hatta H, Yokogoshi H. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors 2006;26:201-8.
[76] Seo YC, Choi WY, Kim JS, Lee CG, Ahn JH, Cho HY, Lee SH, Cho JS, Joo SJ, Lee HY. Enhancement of the Cognitive Effects of γ-Aminobutyric Acid from Monosodium Glutamate Fermentation by Lactobacillus sakei B2-16. Food Biotechnol 2012;26:29-44.
[77] Reid S, Ryu JK, Kim Y, Jeon BH. The Effects of Fermented Laminaria japonica on Short-Term Working Memory and Physical Fitness in the Elderly. Evidence-based complementary and alternative medicine. eCAM 2018.
[78] Danilov A, Kurganova J. Melatonin in Chronic Pain Syndromes. Pain Ther 2016;5:1-17.
[79] Cardinali DP, Srinivasan V, Brzezinski A, Brown GM. Melatonin and its analogs in insomnia and depression. J Pineal Res 2012;52:365-75.
[80] Antón-Tay F, Díaz JL, Fernández-Guardiola A. On the effect of melatonin upon human brain. Its possible therapeutic implications. Life Sci I 1971;10:841-50.
[81] Jacob S, Poeggeler B, Weishaupt JH, Sirén AL, Hardeland R, Bähr M, Ehrenreich H. Melatonin as a candidate compound for neuroprotection in amyotrophic lateral sclerosis (ALS): high tolerability of daily oral melatonin administration in ALS patients. J Pineal Res 2002;33:186-7.
[82] Weishaupt JH, Bartels C, Pölking E, Dietrich J, Rohde G, Poeggeler B, Mertens N, Sperling S, Bohn M, Hüther G, Schneider A, Bach A, Sirén AL, Hardeland R, Bähr M, Nave KA, Ehrenreich H. Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J Pineal Res 2006;41:313-23.
[83] Chahbouni M, Escames G, López LC, Sevilla B, Doerrier C, Muñoz-Hoyos A, Molina-Carballo A, Acuña-Castroviejo D. Melatonin treatment counteracts the hyperoxidative status in erythrocytes of patients suffering from Duchenne muscular dystrophy. Clin Biochem 2011;44:853-8.
[84] López-González A, Álvarez-Sánchez N, Lardone PJ, Cruz-Chamorro I, Martínez-López A, Guerrero JM, Reiter RJ, Carrillo-Vico A. Melatonin treatment improves primary progressive multiple sclerosis: a case report. J Pineal Res 2015;58:173-7.
[85] Peres MF, Zukerman E, da Cunha Tanuri F, Moreira FR, Cipolla-Neto J. Melatonin, 3 mg, is effective for migraine prevention. Neurology 2004;63:757. wnl.0000134653.35587.24
[86] Kiecolt-Glaser JK, Belury MA, Andridge R, Malarkey WB, Glaser R. Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial. Brain Behav Immun 2011;25:1725-34. bbi.2011.07.229
[87] Mattson MP. Diet – Brain Connections. Impact on Memory, Mood, Aging and Disease, 1st Edition. New York: Springer 2022.
[88] Dangour AD, Allen E, Elbourne D, Fletcher A, Richards M, Uauy R. Fish consumption and cognitive function among older people in the UK: baseline data from the OPAL study. J Nutr Health Aging 2009;13:198-202.
[89] da Silva TM, Munhoz RP, Alvarez C, Naliwaiko K, Kiss A, Andreatini R, Ferraz AC. Depression in Parkinson’s disease: a double-blind, randomized, placebo-controlled pilot study of omega-3 fatty-acid supplementation. J Affect Disord 2008;111:351-9.
[90] Otsuka M, Yamaguchi K, Ueki A. Similarities and differences between Alzheimer’s disease and vascular dementia from the viewpoint of nutrition. Ann N Y Acad Sci 2002;977:155-6.
[91] Kennedy DO. B vitamins and the brain: mechanisms, dose and efficacy – a review. Nutrients 2016;8:68.
[92] Sechi G, Sechi E, Fois C, Kumar N. Advances in clinical determinants and neurological manifestations of B vitamin deficiency in adults. Nutr Rev 2016;74:281-300.
[93] Smith AD, Refsum H, Bottiglieri T, Fenech M, Hooshmand B, McCaddon A, Miller JW, Rosenberg IH, Obeid R. Homocysteine and dementia: an international consensus statement. Alzheimers Dis 2018;62:561-70.
[94] Bonke D, Nickel B. Improvement of fine motoric movement control by elevated dosages of vitamin B1, B6, and B12 in target shooting. Int J Vitam Nutr Res Suppl 1989;30:198-204.
[95] Calderón‐Ospina CA, Nava‐Mesa MO. B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. CNS Neurosci Ther 2020;26:5-13.
[96] Langan RC, Goodbred AJ. Vitamin B12 Deficiency: Recognition and Management. Am Fam Physician 2017;96:384-9.
[97] Martin PR. Molecular mechanisms of thiamine utilization. Curr Mol Med 2001;1:197-207.
[98] Zempleni J, Suttie JW, Gregory III JF, Stover PJ, eds. Handbook of vitamins. CRC Press 2013;29.
[99] Kumar N. Neurologic aspects of cobalamin (B12) deficiency. Handb Clin Neurol 2014;120:915-26.
[100] Momosaki K, Kido J, Matsumoto S, Taniguchi A, Akiyama T, Sawada T, Ozasa S, Nakamura K. The Effect of S-Adenosylmethionine Treatment on Neurobehavioral Phenotypes in Lesch-Nyhan Disease: A Case Report. Case Rep Neurol 2019;11:256-64.
[101] Silveri MM, Parow AM, Villafuerte RA, Damico KE, Goren J, Stoll AL, Cohen BM, Renshaw PF. S-adenosyl-L-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjects. Biol Psychiatry 2003;54:833-9.
[102] Williams AL, Girard C, Jui D, Sabina A, Katz DL. S-adenosylmethionine (SAMe) as treatment for depression: a systematic review. Clin Invest Med 2005;28:132-9.
[103] Sood A, Prasad K, Croghan IT, Schroeder DR, Ehlers SL, Ebbert JO. S-adenosyl-L-methionine (SAMe) for smoking abstinence: a randomized clinical trial. J Altern Complement Med 2012;18:854-9.
[104] Di Rocco A, Rogers JD, Brown R, Werner P, Bottiglieri T. S-Adenosyl-Methionine improves depression in patients with Parkinson’s disease in an open-label clinical trial. Mov Disord 2000;15:1225-9.<1225::aid-mds1025>;2-a
[105] Sarris J, Thomson R, Hargraves F, Eaton M, de Manincor M, Veronese N, Solmi M, Stubbs B, Yung AR, Firth J. Multiple lifestyle factors and depressed mood: a cross-sectional and longitudinal analysis of the UK Biobank (N = 84,860). BMC Med 2020;18:354.
[106] Buist R. The therapeutic predictability of tryptophan and tyrosine in the treatment of depression. Int J Clin Nutr Rev 1983;3:1-3.
[107] De Luca V, Viggiano E, Messina G, Viggiano A, Borlido C, Viggiano A, Monda M. Peripheral amino Acid levels in schizophrenia and antipsychotic treatment. Psychiatry Investig 2008;5:203-8.
[108] Green AR, Aronson JK, Cowen PJ. The pharmacokinetics of L-tryptophan following its intravenous and oral administration. Br J Clin Pharmacol 1985;20:317-21.
[109] Ozawa M, Ninomiya T, Ohara T, Hirakawa Y, Doi Y, Hata J, Uchida K, Shirota T, Kitazono T, Kiyohara Y. Self-reported dietary intake of potassium, calcium, and magnesium and risk of dementia in the Japanese: the Hisayama Study. J Am Geriatr Soc 2012;60:1515-20.
[110] Barbagallo M, Belvedere M, Di Bella G, Dominguez LJ. Altered ionized magnesium levels in mild-to-moderate Alzheimer’s disease. Magnes Res 2011;24:S115-21.
[111] Muir KW, Lees KR, Ford I, Davis S; Intravenous Magnesium Efficacy in Stroke (IMAGES) Study Investigators. Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial. Lancet 2004;363:439-45.
[112] Morris G, Gamage E, Travica N, Berk M, Jacka FN, O’Neil A, Puri BK, Carvalho AF, Bortolasci CC, Walder K, Marx W. Polyphenols as adjunctive treatments in psychiatric and neurodegenerative disorders: Efficacy, mechanisms of action, and factors influencing inter-individual response. Free Radic Biol Med 2021;172:101-22. freeradbiomed.2021.05.036
[113] Hemanth Kumar B, Arun Reddy R, Mahesh Kumar J, Dinesh Kumar B, Diwan PV. Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia. Can J Physiol Pharmacol 2017;95:32-42.
[114] de Oliveira NG, Teixeira IT, Theodoro H, Branco CS. Dietary total antioxidant capacity as a preventive factor against depression in climacteric women. Dement Neuropsychol 2019;13:305-11.
[115] Rohdewald P. A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther 2002;40:158-68.
[116] Verlaet AA, Ceulemans B, Verhelst H, Van West D, De Bruyne T, Pieters L, Savelkoul HF, Hermans N. Effect of Pycnogenol® on attention-deficit hyperactivity disorder (ADHD): study protocol for a randomised controlled trial. Trials 2017;18:145.
[117] Lorenzo JM, Putnik P, Kovačević DB, Petrović M, Munekata PE, Gómez B, Marszałek K, Roohinejad S, Barba FJ. Silymarin compounds: Chemistry, innovative extraction techniques and synthesis. Stud Nat Prod Chem 2020;64:111-30.
[118] Haddadi R, Shahidi Z, Eyvari-Brooshghalan S. Silymarin and neurodegenerative diseases: Therapeutic potential and basic molecular mechanisms. Phytomedicine 2020;79:153320.
[119] Devi KP, Malar DS, Braidy N, Nabavi SM, Nabavi SF. A Mini Review on the Chemistry and Neuroprotective Effects of Silymarin. Current Drug Targets 2017;18:1529-36.
[120] Guo H, Cao H, Cui X, Zheng W, Wang S, Yu J, Chen Z. Silymarin’s inhibition and treatment effects for Alzheimer’s disease. Molecules 2019;24:1748.
[121] Lopresti AL. Curcumin for neuropsychiatric disorders: a review of in vitro, animal and human studies. J Psychopharmacol 2017;31:287-302.
[122] Fusar-Poli L, Vozza L, Gabbiadini A, Vanella A, Concas I, Tinacci S, Petralia A, Signorelli MS, Aguglia E. Curcumin for depression: a meta-analysis. Crit Rev Food Sci Nutr 2020;60:2643-53. 3260
[123] Zhu LN, Mei X, Zhang ZG, Xie YP, Lang F. Curcumin intervention for cognitive function in different types of people: A systematic review and meta‐analysis. Phytother Res 2019;33:524-33.
[124] Voulgaropoulou SD, Van Amelsvoort TA, Prickaerts J, Vingerhoets C. The effect of curcumin on cognition in Alzheimer’s disease and healthy aging: A systematic review of pre-clinical and clinical studies. Brain Res 2019;1725:146476.
[125] Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, Aisen PS, Turner RS. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J Neuroinflammation 2017;14:1-0.
[126] Komorowska J, Wątroba M, Szukiewicz D. Review of beneficial effects of resveratrol in neurodegenerative diseases such as Alzheimer’s disease. Adv Med Sci 2020;65:415-23.
[127] Mattioli R, Francioso A, Mosca L, Silva P. Anthocyanins: A comprehensive review of their chemical properties and health effects on cardiovascular and neurodegenerative diseases. Molecules 2020;25:3809.
[128] Zaplatic E, Bule M, Shah SZ, Uddin MS, Niaz K. Molecular mechanisms underlying protective role of quercetin in attenuating Alzheimer’s disease. Life Sci 2019;224:109-19.
[129] Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, Liu H, Yin Y. Quercetin, Inflammation and Immunity. Nutrients 2016;8:167.
[130] Banerjee S, Anand U, Ghosh S, Ray D, Ray P, Nandy S, Deshmukh GD, Tripathi V, Dey A. Bacosides from Bacopa monnieri extract: An overview of the effects on neurological disorders. Phytother Res 2021;35:5668-79.
[131] Dar NJ, MuzamilAhmad. Neurodegenerative diseases and Withania somnifera (L.): An update. J Ethnopharmacol 2020;256:112769.
[132] Sharma V, Sharma R, Gautam DS, Kuca K, Nepovimova E, Martins N. Role of Vacha (Acorus calamus Linn.) in Neurological and Metabolic Disorders: Evidence from Ethnopharmacology, Phytochemistry, Pharmacology and Clinical Study. J Clin Med 2020;9:1176.
[133] Simpson T, Pase M, Stough C. Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain. Evid Based Complement Alternat Med 2015;2015:615384.
[134] Mishra S, Srivastava S, Tripathi RD, Govindarajan R, Kuriakose SV, Prasad MN. Phytochelatin synthesis and response of antioxidants during cadmium stress in Bacopa monnieri L. Plant Physiol Biochem 2006;44:25-37. plaphy.2006.01.007
[135] Rasool M, Malik A, Qureshi MS, Manan A, Pushparaj PN, Asif M, Qazi MH, Qazi AM, Kamal MA, Gan SH, Sheikh IA. Recent updates in the treatment of neurodegenerative disorders using natural compounds. Evid Based Complement Alternat Med 2014;2014:979730.