Possiamo prevenire l’invecchiamento del nostro cervello?

•   Tutti noi vorremmo conservare il più a lungo possibile la memoria, le capacità di apprendimento, di ragionamento e di linguaggio. In altre parole, evitare il declino cognitivo.

•   Praticare regolarmente attività fisica, adottare stili di vita salubri, mantenere in esercizio la mente e stabilire proficue relazioni sociali ecc., sono tutte insostituibili azioni preventive contro il declino cognitivo.

•   Negli ultimi anni la scienza ha identificato i vantaggi di determinate molecole, presenti in alcuni alimenti e negli integratori, per preservare la salute del cervello e diminuire il rischio di contrarre malattie croniche dovute all’invecchiamento.

Le vitamine B e C

Nelle persone con declino cognitivo (Nota 1) e malattie neurodegenerative, come l’Alzheimer, le ricerche cliniche hanno rilevato insufficienti livelli ematici di vitamine del gruppo B e di vitamina C (1, 2, 3).

Uno studio pubblicato dalla rivista Nature - scientific report  mette in evidenza queste carenze vitaminiche e la coesistenza con alte concentrazioni ematiche di omocisteina (3).

La cosiddetta iperomocisteinemia è infatti un fattore di rischio per il declino cognitivo, le malattie neurodegenerative, cardiovascolari, renali ecc. (3, 4). 

Questi fenomeni fisiopatologici vengono aggravati dalle alterazioni delle funzioni mitocondriali (Nota 2) (3, 4-15) e dall’ossido-infiammazione (Nota 2) (16-33), che sono strettamente interconnessi all’iperomocisteinemia (3, 11, 15, 34-36).

Nel loro insieme questi meccanismi alimentano un circolo vizioso con la senescenza cellulare (16, 37-43), ed altri processi dell’invecchiamento che vanno a destabilizzare le strutture nervose e vascolari del cervello (16, 37, 44, 45, 46).

Per questo, gli studi clinici sottolineano l’importanza di mantenere adeguati livelli ematici di folati, vitamina B6 e B12, che regolarizzano il metabolismo dell’omocisteina e contribuiscono a ridurre il rischio delle malattie neurodegenerative e cardiovascolari  (47, 48, 49, 50-62).

A queste attività neuroprotettive di vitamina B12 (54, 55), folati / acido folico (54, 56), e vitamina C (16, 37, 63, 64), si aggiungono importanti benefici sulla composizione del microbiota intestinale, che risulta importante anche per le funzioni del cervello e di altri organi (65-72).

Ricordiamo che l’acido folico è la forma più adatta per somministrare i folati attraverso l’integrazione orale (54, 56). I folati sono presenti in verdure a foglia verde, legumi, frattaglie, uova ecc., ma il processo di cottura può distruggere molto la quantità disponibile in questi alimenti (54, 56).

Da questo deriva l’alto rischio di insufficiente apporto / carenza di folati (54, 56). 

Oltre tutto queste vitamine idrosolubili  (65, 67, 73, 74) dimostrano una serie di benefici metabolici (74, 75, 76), cerebrovascolari e cardiovascolari (34), che contribuiscono ulteriormente ad abbassare il rischio di declino cognitivo e delle altre malattie neurodegenerative (54, 55, 56, 73, 78, 79, 80).

Inoltre hanno la capacità di rallentare l’invecchiamento biologico del nostro organismo (81-91).    

Per la loro importanza, viene raccomandato il monitoraggio dei livelli ematici di B12 e di folati nei soggetti a rischio di carenza, es.: vegani, vegetariani, atleti, anziani ecc. (54, 55, 56, 66, 67, 79, 80).

Ulteriori molecole con funzioni neuroprotettive

Con l’obiettivo di combattere l’ossido-infiammazione e la disfunzione mitocondriale contro il declino cognitivo e migliorare la performance mentale, risultano attive ulteriori molecole (11, 73, 92).

Vitamine liposolubili

Oltre alle già citate vitamine B e C, sono di particolare importanza le vitamine E e D, ed i carotenoidi precursori di vitamina A (4, 11, 48, 92-95).

Queste vitamine liposolubili contribuiscono a mantenere, ed aumentare le difese antiossidanti dell’organismo, e svolgere altre funzioni indispensabili per le strutture cerebrali e dell’intero organismo (4, 11, 48, 92-95).

Negli studi clinici queste vitamine hanno dimostrato di ridurre l’insorgenza e la progressione dei disturbi neurocognitivi (30, 73, 92, 96, 97, 98), migliorare la composizione del microbiota intestinale e rallentare l’invecchiamento biologico (86, 92, 99-114).

Inoltre, vitamina A, C, D, E, con altri antiossidanti glutatione, coenzima Q10, polifenoli, svolgono significativi benefici anche per conservare la salute orale, di estrema importanza per la prevenzione delle malattie neurodegenerative (120-126).

Polifenoli

I polifenoli come  curcumina, quercetina, resveratrolo ecc. (11, 13, 92, 95, 127-131) sono una classe di molecole vegetali molto vasta, ed attiva contro vari meccanismi dell’invecchiamento dell’organismo (11, 92, 99, 132-139).

Nei numerosi studi dedicati, il resveratrolo ha dimostrato significative attività neuroprotettive e promettenti risultati clinici per prevenire e rallentare il declino cognitivo (11, 13, 14, 15, 92, 95, 129, 140-151).

Per il resveratrolo sono documentati vari benefici:

- rallenta l’invecchiamento biologico (133, 150, 151, 152);

- migliora le attività metaboliche e cardiovascolari (34, 153-158);

- attenua i disturbi collegati al declino degli estrogeni dopo la menopausa, inclusi i problemi cognitivi (43, 150, 151, 153, 159, 160);

- previene la disbiosi intestinale (34, 66,  76, 77, 153, 154, 159, 161-164);

- contribuisce a equilibrare il ritmo sonno-veglia, di estrema importanza per la cognitività (165).

Coenzima Q10

Bassi livelli di questo potente antiossidante/antinfiammatorio sono associati in modo significativo al declino delle funzioni cognitive (166).

L’integrazione mirata di coenzima Q10 incrementa in modo significativo le difese antiossidanti endogene del nostro organismo, che tendono a diminuire progressivamente dopo i 30 anni d’età (11, 167).

Il coenzima Q10 dimostra promettenti effetti su vari disturbi neurologici e della cognitività (13, 14, 15, 95, 166-172), oltre alle numerose prove cliniche sulle problematiche spesso coesistenti, come depressione, stanchezza cronica (173), fibromialgia (166, 169, 174, 175), ed i disturbi metabolici e cardiovascolari (11, 34, 73-77, 176, 177, 178).

Nell’uomo, il coenzima Q10 protegge e normalizza significativamente la sintesi del testosterone nelle cellule Leydig (179).

Un’effetto svolto anche dai polifenoli, tramite il miglioramento di vari parametri metabolici che possono abbassare i livelli di testosterone, come  avviene in caso di sovrappeso/obesità, diabete ecc.. (76, 77, 180).

I ridotti livelli di testosterone, infatti, possono compromettere anche la prestazione cognitiva, come la memoria e le funzioni esecutive, oltre a generare vari disturbi generali (181-185).

Altre sostanze ad azione neuroprotettiva  

Gli Acidi grassi omega 3 all’azione antiossidante / antinfiammatoria associano importanti benefici per il microbiota intestinale (109, 186), e per rallentare l’invecchiamento biologico dell’organismo (48, 73, 92, 104, 129, 187-191).

Recenti studi confermano il significativo contributo degli acidi grassi omega 3 per ridurre il rischio di declino cognitivo (192, 193, 194) e per la relativa gestione clinica (195, 196-201). 

La Creatina (73, 202, 203, 204) e la carnitina (73, 205) hanno interessanti effetti sulla performance cognitiva (73, 202, 203, 204). Sono entrambe molecole a rischio di insufficiente apporto per le persone che non consumano o limitano gli alimenti di origine animale (73, 202-205). 

Recenti studi documentano il contributo del magnesio (73, 206, 207, 208) e della melatonina (73, 209), per citare solo alcune delle principali molecole con effetti neuroprotettivi.

Ricerca e innovazione Mitochon srl

Da alcuni anni la ricerca dell’azienda italiana Mitochon srl https://www.mitochon.it/ ha creato una intera linea di prodotti per l’antiaging cutaneo e sistemico, efficaci e sicuri.

L’integratore orosolubile Mitofast bit.ly/3VUlGkS permette di (210, 211):

•   incrementare in modo significativo le difese antiossidanti dell’organismo es.: coenzima Q10 (+184%), glutatione totale (+53%) e vitamina E (+ 11%);

•   ridurre i livelli plasmatici di omocisteina (-13%);

•   ottenere concreti risultati antiaging e migliorare il benessere generale percepito, dopo almeno 4 settimane di assunzione;

•   contribuire a prevenire ed attenuare i vari disturbi clinici dipendenti dall’età;

•   essere associato all’integratore liquido Mitofast B12  bit.ly/4d5ll4P , per un’azione sinergica con la vitamina B12 (54, 55, 56)

Una bustina monodose di Mitofast® bit.ly/3VUlGkS contiene:

- Resveratrolo (40 mg);

- Coenzima Q10 (100 mg);

- Acido folico (400 mcg);

- Vitamina C (20 mg); 

- N-acetilglucosamina (150 mg) per promuovere la sintesi di acido ialuronico, indispensabile per il trofismo cutaneo (212, 213);

- N-acetilcisteina (150 mg) per incrementare le concentrazioni di glutatione, il principale antiossidante del corpo umano (210, 211, 214, 215).

La N-acetilcisteina (214, 215) svolge anche attività neuroprotettive, oltre a migliorare i parametri metabolici, vascolari, ed delle funzioni cognitive (34, 37, 95, 216, 217, 218, 219). 

Conclusioni

•   Gli effetti trasversali di specifici antiossidanti / antinfiammatorie, derivanti dall’alimentazione e da specifici integratori, possono contribuire a conservare la performance cognitiva e rallentare l’invecchiamento biologico.

•   I benefici di queste molecole devono essere associati agli insostituibili vantaggi dell’attività fisica e degli stili di vita (223), riconosciuti come  fondamentali per preservare la memoria, le altre funzioni cognitive e la salute generale.

•   Mitofast bit.ly/3VUlGkS permette di assumere facilmente (210, 220, 221) appropriate quantità di ingredienti attivi di provata efficacia contro l’invecchiamento, ed i disturbi collegati (210), inclusi quelli della cognitività (224).

Nota 1 (1, 2)

Il declino cognitivo lieve si manifesta con uno o più dei seguenti sintomi:

perdita di memoria, alterazioni delle funzioni esecutive, difficoltà ad intraprendere azioni o compiti, rallentamento del pensiero, cambiamenti di umore e di personalità, deficit del linguaggio.

Nel declino cognitivo lieve i sintomi non sono tali da ridurre le capacità di svolgere i compiti quotidiani e mantenere l’indipendenza personale, che sono invece compromessi nelle forme più gravi di demenza.

Il declino cognitivo lieve espone ad un maggior rischio di sviluppare forme più gravi di perdita della cognitività.

Oltre all’invecchiamento dell’organismo, i principali fattori di rischio comprendono: predisposizione genetica; malattie croniche, es.: cardiometaboliche, respiratorie, osteoarticolari; disturbi del sonno e dell’umore; malattie neurologiche; carenze vitaminiche; trattamento polifarmacologici; abitudini di vita, es.: sedentarietà, eccessivo consumo di alcol ecc..  

Nota 2 (3, 4-33)

Metabolismo cerebrale - disfunzione mitocondriale - stress ossidativo - infiammazione cronica

Il cervello rappresenta solo il 2% del peso corporeo totale e consuma il 20% del consumo totale di ossigeno, il 25% del consumo totale di glucosio corporeo.

Queste grandi quantità di ossigeno e glucosio consumate dal cervello sono necessarie per produrre l'energia necessaria ai neuroni per ripristinare i loro gradienti elettrochimici, che vengono dissipati durante la neurotrasmissione.

I neuroni assorbono il 70% dell’energia consumata dal cervello, ed il restante quantitativo viene ripartito tra astrociti, microglia ecc..

Di conseguenza il deterioramento multicausale delle funzioni mitocondriale costituisce un fattore di rischio che predispone all’insorgenza, ed alla progressione dei disturbi neurodegenerativi.

La disfunzione mitocondriale risulta infatti presente in modo precoce nel declino cognitivo, ancora prima dell’instaurarsi dell’accumulo di amiloide e dei grovigli microfibrillari nei neuroni.

Lo stress ossidativo e le alterazioni ossidative di proteiche e lipidiche sono facilitate anche dall’abbassamento delle difese antiossidanti endogene che, nel loro insieme, innescano la progressione dell’infiammazione cronica (inflammaging) ed altre alterazioni riconducibili agli hallmarks of aging.

Oltre ai neuroni, questi eventi danneggiano gli astrociti e le cellule dei vasi sanguigni cerebrali, in primo luogo per il ridotto apporto energetico causato dai danni mitocondriali e l’aumenta produzione di specie reattive dell’ossigeno.

Anche per i disturbi neurodegenerativi si consolidano le strategie che mirano a proteggere e rigenerare le funzioni mitocondriali a fini preventivi e terapeutici.

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136. Saliev, T.; Singh, P.B. Targeting Senescence: A Review of Senolytics and Senomorphics in Anti-Aging Interventions. Biomolecules 2025, 15, 860. https://doi.org/10.3390/biom15060860

137. Yaskolka Meir A, Keller M, Hoffmann A, Rinott E, Tsaban G, Kaplan A, Zelicha H, Hagemann T, Ceglarek U, Isermann B, Shelef I, Blüher M, Stumvoll M, Li J, Haange SB, Engelmann B, Rolle-Kampczyk U, von Bergen M, Hu FB, Stampfer MJ, Kovacs P, Liang L, Shai I. The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial. BMC Med. 2023 Sep 25;21(1):364. doi: 10.1186/s12916-023-03067-3.

138. Pereira, Q.C.; dos Santos, T.W.; Fortunato, I.M.; Ribeiro, M.L. The Molecular Mechanism of Polyphenols in the Regulation of Ageing Hallmarks. Int. J. Mol. Sci. 2023, 24, 5508. https://doi.org/10.3390/ijms24065508

139. Pereira QC, Fortunato IM, Oliveira FS, Alvarez MC, Santos TWD, Ribeiro ML. Polyphenolic Compounds: Orchestrating Intestinal Microbiota Harmony during Aging. Nutrients. 2024 Apr 5;16(7):1066. doi: 10.3390/nu16071066. 

140. Buglio DS, Marton LT, Laurindo LF, Guiguer EL, Araújo AC, Buchaim RL, Goulart RA, Rubira CJ, Barbalho SM. The Role of Resveratrol in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review. J Med Food. 2022 Aug;25(8):797-806. doi: 10.1089/jmf.2021.0084.

141. Morkovin, E.; Litvinov, R.; Koushner, A.; Babkov, D. Resveratrol and Extra Virgin Olive Oil: Protective Agents Against Age-Related Disease. Nutrients 2024, 16, 4258. https://doi.org/10.3390/nu16244258

142. Islam F, Nafady MH, Islam MR, Saha S, Rashid S, Akter A, Or-Rashid MH, Akhtar MF, Perveen A, Md Ashraf G, Rahman MH, Hussein Sweilam S. Resveratrol and neuroprotection: an insight into prospective therapeutic approaches against Alzheimer's disease from bench to bedside. Mol Neurobiol. 2022 Jul;59(7):4384-4404. doi: 10.1007/s12035-022-02859-7.

143. Subhan I, Siddique YH. Resveratrol: Protective Agent Against Alzheimer's Disease. Cent Nerv Syst Agents Med Chem. 2024;24(3):249-263. doi: 10.2174/0118715249287167240222081517.

144. Wang Q, Yu Q, Wu M. Antioxidant and neuroprotective actions of resveratrol in cerebrovascular diseases. Front Pharmacol. 2022 Sep 5;13:948889. doi: 10.3389/fphar.2022.948889. 

145. Wei H, Fang G, Song W, Cao H, Dong R, Huang Y. Resveratrol's bibliometric and visual analysis from 2014 to 2023. Front Plant Sci. 2024 Oct 8;15:1423323. doi: 10.3389/fpls.2024.1423323. 

146. Yadegar S, Mohammadi F, Yadegar A, Mohammadi Naeini A, Ayati A, Milan N, Tayebi A, Seyedi SA, Nabipoorashrafi SA, Rabizadeh S, Esteghamati A, Nakhjavani M. Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review. Phytother Res. 2024 May;38(5):2448-2461. doi: 10.1002/ptr.8171. 

147. Menegas S, Keller GS, Possamai-Della T, Aguiar-Geraldo JM, Quevedo J, Valvassori SS. Potential mechanisms of action of resveratrol in prevention and therapy for mental disorders. J Nutr Biochem. 2023 Nov;121:109435. doi: 10.1016/j.jnutbio.2023.109435. 

148. Naik RA, Rajpoot R, Koiri RK, Bhardwaj R, Aldairi AF, Johargy AK, Faidah H, Babalghith AO, Hjazi A, Alsanie WF, Alamri AS, Alhomrani M, Alsharif A, Shkodina A, Singh SK. Dietary supplementation and the role of phytochemicals against the Alzheimer's disease: Focus on polyphenolic compounds. J Prev Alzheimers Dis. 2025 Jan;12(1):100004. doi: 10.1016/j.tjpad.2024.100004.

149. de Lima EP, Laurindo LF, Catharin VCS, Direito R, Tanaka M, Jasmin Santos German I, Lamas CB, Guiguer EL, Araújo AC, Fiorini AMR, Barbalho SM. Polyphenols, Alkaloids, and Terpenoids Against Neurodegeneration: Evaluating the Neuroprotective Effects of Phytocompounds Through a Comprehensive Review of the Current Evidence. Metabolites. 2025 Feb 13;15(2):124. doi: 10.3390/metabo15020124.

150. Mini-Review Resveratrolo Peri- Post-Menopausa https://www.mitochon.it/peri-e-post-menopausa-novita-sui-vantaggi-dellintegrazionealimentare-mirata/

151. Mini-Review Resveratrolo effetti neuroprotettivi https://www.mitochon.it/cervello-e-cognitivita-effetti-neuroprotettivi-del-resveratrolo/

152. Zhang S, Kiarasi F. Therapeutic effects of resveratrol on epigenetic mechanisms in age-related diseases: A comprehensive review. Phytother Res. 2024 May;38(5):2347-2360. doi: 10.1002/ptr.8176.

153. Mini-Review Sovrappenso / Obesità - Resveratrolo - Antiossidanti 2025 https://www.mitochon.it/sovrappeso-obesita-quale-contributo-dal-resveratrolo-ed-altri-antiossidanti/?v=0d149b90e739

154. Mini-Review Stress psicofisico - Antiossidanti / Neuroprotettori 2025 https://www.mitochon.it/stress-psicofisico-attualita-sulluso-appropriato-di-antiossidanti-neuroprotettivi/?v=0d149b90e739

155. Koushki M, Farahani M, Yekta RF, Frazizadeh N, Bahari P, Parsamanesh N, Chiti H, Chahkandi S, Fridoni M, Amiri-Dashatan N. Potential role of resveratrol in prevention and therapy of diabetic complications: a critical review. Food Nutr Res. 2024 Apr 30;68. doi: 10.29219/fnr.v68.9731.

156. Wang J, Zhang J, Yu ZL, Chung SK, Xu B. The roles of dietary polyphenols at crosstalk between type 2 diabetes and Alzheimer's disease in ameliorating oxidative stress and mitochondrial dysfunction via PI3K/Akt signaling pathways. Ageing Res Rev. 2024 Aug;99:102416. doi: 10.1016/j.arr.2024.102416.

157. Yavari, M.; Kalupahana, N.S.; Harris, B.N.; Ramalingam, L.; Zu, Y.; Kahathuduwa, C.N.; Moustaid-Moussa, N. Mechanisms Linking Obesity, Insulin Resistance, and Alzheimer’s Disease: Effects of Polyphenols and Omega-3 Polyunsaturated Fatty Acids. Nutrients 2025, 17, 1203. https://doi.org/10.3390/nu17071203

158. Hattori Y, Kakino Y, Hattori Y, Iwashita M, Uchiyama H, Noda K, Yoshimoto T, Iida H, Ihara M. Long-Term Resveratrol Intake for Cognitive and Cerebral Blood Flow Impairment in Carotid Artery Stenosis/Occlusion. J Stroke. 2024 Jan;26(1):64-74. doi: 10.5853/jos.2023.02733.

159. Mini-Review Osteoporosi - Resveratrolo 2025 https://www.mitochon.it/osteoporosi-nel-post-menopausa-attualita-sul-ruolo-del-resveratrolo-altri-antiossidanti-e-vitamine/?v=0d149b90e739

160. Thaung Zaw JJ, Howe PR, Wong RH. Long-term effects of resveratrol on cognition, cerebrovascular function and cardio-metabolic markers in postmenopausal women: A 24-month randomised, double-blind, placebo-controlled, crossover study. Clin Nutr. 2021 Mar;40(3):820-829. doi: 10.1016/j.clnu.2020.08.025.

161. Nemzer, B.V.; Al-Taher, F.; Kalita, D.; Yashin, A.Y.; Yashin, Y.I. Health-Improving Effects of Polyphenols on the Human Intestinal Microbiota: A Review. Int. J. Mol. Sci. 2025, 26, 1335. https://doi.org/10.3390/ijms26031335

162. Meyer C, Brockmueller A, Ruiz de Porras V, Shakibaei M. Microbiota and Resveratrol: How Are They Linked to Osteoporosis? Cells. 2024 Jul 3;13(13):1145. doi: 10.3390/cells13131145.

163. Nakadate, K.; Ito, N.; Kawakami, K.; Yamazaki, N. Anti-Inflammatory Actions of Plant-Derived Compounds and Prevention of Chronic Diseases: From Molecular Mechanisms to Applications. Int. J. Mol. Sci. 2025, 26, 5206. https://doi.org/10.3390/ijms26115206

164. Chen X, Zhang J, Yin N, Wele P, Li F, Dave S, Lin J, Xiao H, Wu X. Resveratrol in disease prevention and health promotion: A role of the gut microbiome. Crit Rev Food Sci Nutr. 2024;64(17):5878-5895. doi: 10.1080/10408398.2022.2159921. 

165. Zhu W, Gong A, Zhang B, Cheng H, Huang L, Wu X, Zhang D, Dai W, Li S, Xu H. The Chronobiological and Neuroprotective Mechanisms of Resveratrol in Improving Sleep. Mediators Inflamm. 2025 Mar 19;2025:4954030. doi: 10.1155/mi/4954030. 

166. Fernández-Portero C, Amián JG, Bella R, López-Lluch G, Alarcón D. Coenzyme Q10 Levels Associated With Cognitive Functioning and Executive Function in Older Adults. J Gerontol A Biol Sci Med Sci. 2023 Jan 26;78(1):1-8. doi: 10.1093/gerona/glac152.

167. Sood B, Patel P, Keenaghan M. Coenzyme Q10. [Updated 2024 Jan 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK531491/ 

168. Sharma H, Binte Ibrahim S, Al Noman A, Zohora UFT, Shifa FA, Siddika S, Tasneem S, Al Azad M, Pathak R. The Potential of Coenzyme Q10 in Alzheimer's Disease: Reducing IL-17 Induced Inflammation and Oxidative Stress for Neuroprotection. Curr Drug Res Rev. 2025 Apr 24. doi: 10.2174/0125899775373406250411104442.

169. Jiang, X.; Guo, Y.; Cui, L.; Huang, L.; Guo, Q.; Huang, G. Study of Diet Habits and Cognitive Function in the Chinese Middle-Aged and Elderly Population: The Association between Folic Acid, B Vitamins, Vitamin D, Coenzyme Q10 Supplementation and Cognitive Ability. Nutrients 2023, 15, 1243. https://doi.org/10.3390/nu15051243

170. Ebrahimi A, Kamyab A, Hosseini S, Ebrahimi S, Ashkani-Esfahani S. Involvement of Coenzyme Q10 in Various Neurodegenerative and Psychiatric Diseases. Biochem Res Int. 2023 Nov 1;2023:5510874. doi: 10.1155/2023/5510874.

171. Mantle, D.; Hargreaves, I.P. Mitochondrial Dysfunction and Neurodegenerative Disorders: Role of Nutritional Supplementation. Int. J. Mol. Sci. 2022, 23, 12603. https://doi.org/10.3390/ijms232012603

172. Mantle, D.; Hargreaves, I. Coenzyme Q10 and the Blood–Brain Barrier: An Overview. J. Clin. Med. 2025, 14, 2748. https://doi.org/10.3390/jcm14082748

173. Castro-Marrero J, Segundo MJ, Lacasa M, Martinez-Martinez A, Sentañes RS, Alegre-Martin J. Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2021 Jul 30;13(8):2658. doi: 10.3390/nu13082658. 

174. Badaeva A, Danilov A, Kosareva A, Lepshina M, Novikov V, Vorobyeva Y, Danilov A. Neuronutritional Approach to Fibromyalgia Management: A Narrative Review. Pain Ther. 2024 Oct;13(5):1047-1061. doi: 10.1007/s40122-024-00641-2. 

175. Maggini S, Óvári V, Ferreres Giménez I, Pueyo Alamán MG. Benefits of micronutrient supplementation on nutritional status, energy metabolism, and subjective wellbeing. Nutr Hosp. 2021 Sep 30;38(Spec No2):3-8. English. doi: 10.20960/nh.03788. 

176. Mini-Review Coenzima Q10 2025 https://www.mitochon.it/il-coenzima-q10-novita-per-luso-mirato-nellantiaging-cutaneo-e-per-gli-effetti-sistemici/?v=0d149b90e739

177. Mini-Review Coenzima Q10 https://www.mitochon.it/coenzima-q10-anti-aging-mitocondriale-per-la-pelle/

178. Jiménez-Jiménez, F.J.; Alonso-Navarro, H.; García-Martín, E.; Agúndez, J.A.G. Coenzyme Q10 and Dementia: A Systematic Review. Antioxidants 2023, 12, 533. https://doi.org/10.3390/antiox12020533

179. Akhigbe TM, Fidelis FB, Adekunle AO, Ashonibare VJ, Akorede BA, Shuaibu MS, Hassan SA, Adegbola CA, Ashonibare PJ, Oladapo OM, Adeogun AE, Bamidele SG, Oyedokun PA, Mukolokota M, Kukoyi OS, Oladipo AA, Adelowo OE, Akangbe MD, Hughes JR, Ricken AM, Culty M, Avellar MCW, Akhigbe RE. Does coenzyme Q10 improve semen quality and circulating testosterone level? a systematic review and meta-analysis of randomized controlled trials. Front Pharmacol. 2025 Jan 3;15:1497930. doi: 10.3389/fphar.2024.1497930.

180. Martin, L.J.; Touaibia, M. Prevention of Male Late-Onset Hypogonadism by Natural Polyphenolic Antioxidants. Nutrients 2024, 16, 1815. https://doi.org/10.3390/nu16121815

181. Yeap BB, Flicker L. Testosterone, cognitive decline and dementia in ageing men. Rev Endocr Metab Disord. 2022 Dec;23(6):1243-1257. doi: 10.1007/s11154-022-09728-7. 

182. Zhou J, Dong Q. Testicular aging: mechanism, management and future therapy. Exp Cell Res. 2025 Jun 15;449(2):114603. doi: 10.1016/j.yexcr.2025.114603.

183. Indirli R, Lanzi V, Arosio M, Mantovani G, Ferrante E. The association of hypogonadism with depression and its treatments. Front Endocrinol (Lausanne). 2023 Aug 10;14:1198437. doi: 10.3389/fendo.2023.1198437.

184. Wu Y, Chen F, Zhang T, Miao M, Zhang M, Zhang J, Chang E. The causal association between circulating metabolites and Alzheimer's disease: a systematic review and meta-analysis of Mendelian randomization studies. Metabolomics. 2025 Apr 21;21(3):53. doi: 10.1007/s11306-025-02242-2.

185. Wang B, Liu X, Chen W, Liu L. Effects of androgen replacement therapy on cognitive function in patients with hypogonadism: A systematic review and meta‑analysis. Biomed Rep. 2025 Apr 25;22(6):105. doi: 10.3892/br.2025.1983. 

186. Zinkow A, Grodzicki W, Czerwińska M, Dziendzikowska K. Molecular Mechanisms Linking Omega-3 Fatty Acids and the Gut-Brain Axis. Molecules. 2024 Dec 28;30(1):71. doi: 10.3390/molecules30010071. 

187. Wu D, Jia Y, Liu Y and Shang M (2024) Dose–response relationship of dietary Omega-3 fatty acids on slowing phenotypic age acceleration: a cross-sectional study. Front. Nutr. 11:1424156. doi: 10.3389/fnut.2024.1424156

188. Wattanathorn J, Thukham-Mee W, Tong-Un T, Sangartit W, Somboonporn W, Paholpak P. A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 8-Week Pilot Study of Tuna-Byproduct-Derived Novel Supplements for Managing Cellular Senescence and Cognitive Decline in Perimenopausal and Postmenopausal Women. Antioxidants (Basel). 2025 Apr 27;14(5):520. doi: 10.3390/antiox14050520.

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190. Siopis G, Porter J. Contribution of Biological Age-Predictive Biomarkers to Nutrition Research: A Systematic Review of the Current Evidence and Implications for Future Research and Clinical Practice. Adv Nutr. 2022 Oct 2;13(5):1930-1946. doi: 10.1093/advances/nmac060.

191. Fabian P, Blander G, Deehan R, Torkamani A, Nogal B. Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers. Hum Genomics. 2025 May 24;19(1):61. doi: 10.1186/s40246-025-00756-3.  

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193. Maltais M, de Souto Barreto P, Bowman GL, Smith AD, Cantet C, Andrieu S, Rolland Y. Omega-3 Supplementation for the Prevention of Cognitive Decline in Older Adults: Does It Depend on Homocysteine Levels? J Nutr Health Aging. 2022;26(6):615-620. doi: 10.1007/s12603-022-1809-5.

194. Lin C, Lee SH, Huang CM, Wu YW, Chang YX, Liu HL, Ng SH, Cheng YC, Chiu CC, Wu SC. Cognitive protection and brain entropy changes from omega-3 polyunsaturated fatty acids supplement in late-life depression: A 52-week randomized controlled trial. J Affect Disord. 2024 Apr 15;351:15-23. doi: 10.1016/j.jad.2024.01.205. 

195. Deshmukh GV, Niaz H, Bai R, Kim DH, Kim JW, Asghar J, Ramzan T, Maqbool M, Abushalha NB, Arif S, Khan S. The Role of Omega-3 Fatty Acid Supplementation in Slowing Cognitive Decline Among Elderly Patients With Alzheimer's Disease: A Systematic Review of Randomized Controlled Trials. Cureus. 2024 Nov 10;16(11):e73390. doi: 10.7759/cureus.73390.

196. Naaman RK, Alashmali S, Bakhsh MA, Muqaibil AA, Ghunaim FM, Alattas AH. Association of omega-3 polyunsaturated fatty acids intake and cognitive function in middle-aged and older adults. Nutr Neurosci. 2025 Jun;28(6):649-658. doi: 10.1080/1028415X.2024.2404785.

197. Lin C, Lee SH, Huang CM, Wu YW, Chang YX, Liu HL, Ng SH, Cheng YC, Chiu CC, Wu SC. Cognitive protection and brain entropy changes from omega-3 polyunsaturated fatty acids supplement in late-life depression: A 52-week randomized controlled trial. J Affect Disord. 2024 Apr 15;351:15-23. doi: 10.1016/j.jad.2024.01.205. 

198. Power R, Nolan JM, Prado-Cabrero A, Roche W, Coen R, Power T, Mulcahy R. Omega-3 fatty acid, carotenoid and vitamin E supplementation improves working memory in older adults: A randomised clinical trial. Clin Nutr. 2022 Feb;41(2):405-414. doi: 10.1016/j.clnu.2021.12.004. 

199. Nolan JM, Power R, Howard AN, Bergin P, Roche W, Prado-Cabrero A, Pope G, Cooke J, Power T, Mulcahy R. Supplementation With Carotenoids, Omega-3 Fatty Acids, and Vitamin E Has a Positive Effect on the Symptoms and Progression of Alzheimer's Disease. J Alzheimers Dis. 2022;90(1):233-249. doi: 10.3233/JAD-220556. 

200. Fekete, M.; Lehoczki, A.; Tarantini, S.; Fazekas-Pongor, V.; Csípő, T.; Csizmadia, Z.; Varga, J.T. Improving Cognitive Function with Nutritional Supplements in Aging: A Comprehensive Narrative Review of Clinical Studies Investigating the Effects of Vitamins, Minerals, Antioxidants, and Other Dietary Supplements. Nutrients 2023, 15, 5116. https://doi.org/10.3390/nu15245116

201. Fairbairn P, Dyall SC, Tsofliou F. The effects of multi-nutrient formulas containing a combination of n-3 PUFA and B vitamins on cognition in the older adult: a systematic review and meta-analysis. Br J Nutr. 2023 Feb 14;129(3):428-441. doi: 10.1017/S0007114522001283.

202. Prokopidis K, Giannos P, Triantafyllidis KK, Kechagias KS, Forbes SC, Candow DG. Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2023 Mar 10;81(4):416-427. doi: 10.1093/nutrit/nuac064. 

203. Xu C, Bi S, Zhang W, Luo L. The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis. Front Nutr. 2024 Jul 12;11:1424972. doi: 10.3389/fnut.2024.1424972. Erratum in: Front Nutr. 2025 Feb 17;12:1570800. doi: 10.3389/fnut.2025.1570800. 

204. Sandkühler JF, Kersting X, Faust A, Königs EK, Altman G, Ettinger U, Lux S, Philipsen A, Müller H, Brauner J. The effects of creatine supplementation on cognitive performance-a randomised controlled study. BMC Med. 2023 Nov 15;21(1):440. doi: 10.1186/s12916-023-03146-5.

205. Bigio B, Azam S, Mathé AA, Nasca C. The neuropsychopharmacology of acetyl-L-carnitine (LAC): basic, translational and therapeutic implications. Discov Ment Health. 2024 Jan 2;4(1):2. doi: 10.1007/s44192-023-00056-z. 

206. Kumar A, Mehan S, Tiwari A, Khan Z, Gupta GD, Narula AS, Samant R. Magnesium (Mg2+): Essential Mineral for Neuronal Health: From Cellular Biochemistry to Cognitive Health and Behavior Regulation. Curr Pharm Des. 2024;30(39):3074-3107. doi: 10.2174/0113816128321466240816075041.

207. Mazza, E.; Maurotti, S.; Ferro, Y.; Castagna, A.; Pujia, C.; Sciacqua, A.; Pujia, A.; Montalcini, T. Magnesium: Exploring Gender Differences in Its Health Impact and Dietary Intake. Nutrients 2025, 17, 2226. https://doi.org/10.3390/nu17132226

208. Varga, P.; Lehoczki, A.; Fekete, M.; Jarecsny, T.; Kryczyk-Poprawa, A.; Zábó, V.; Major, D.; Fazekas-Pongor, V.; Csípő, T.; Varga, J.T. The Role of Magnesium in Depression, Migraine, Alzheimer’s Disease, and Cognitive Health: A Comprehensive Review. Nutrients 2025, 17, 2216. https://doi.org/10.3390/nu17132216

209. Kołodziejska, R.; Woźniak, A.; Bilski, R.; Wesołowski, R.; Kupczyk, D.; Porzych, M.; Wróblewska, W.; Pawluk, H. Melatonin—A Powerful Oxidant in Neurodegenerative Diseases. Antioxidants 2025, 14, 819. https://doi.org/10.3390/antiox14070819

210. Mini-Review studio pilota Mitofast https://www.mitochon.it/mitofast-nuovi-ed-importanti-risultati-da-uno-studio-clinico-preliminare/

211. Mini-Review Motivi per l’Integrazione Mirata https://www.mitochon.it/4-motivi-1-per-utilizzare-lintegrazione-mirata-contro-linvecchiamento-cutaneo-e-sistemico/

212. Mini-Review N-acetilglusosamina https://www.mitochon.it/n-acetilglucosamina-nag-per-il-trofismo-cutaneo/

213. Mini-Review Cellule cutanee - senescenza https://www.mitochon.it/le-ultime-scoperte-sullattivita-dei-mitocondri-cellule-cutanee-bersagli-e-risultati-dellantiaging-mitocondriale/

214. Mini-Review Glutatione / NAC https://www.mitochon.it/glutatione-perche-proteggere-le-sue-concentrazioni-cellulari-nellantiaging/

215. Mini-Review N-acetilcisteina https://www.mitochon.it/n-acetilcisteina-nac-dalla-clinica-allanti-aging/

216. Chakraborty S, Shankaranarayana Rao BS, Tripathi SJ. The neuroprotective effects of N-acetylcysteine in psychiatric and neurodegenerative disorders: From modulation of glutamatergic transmission to restoration of synaptic plasticity. Neuropharmacology. 2025 May 23;278:110527. doi: 10.1016/j.neuropharm.2025.110527.

217. Kumar P, Liu C, Hsu JW, Chacko S, Minard C, Jahoor F, Sekhar RV. Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial. Clin Transl Med. 2021 Mar;11(3):e372. doi: 10.1002/ctm2.372.

218. Sekhar RV. GlyNAC Supplementation Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Aging Hallmarks, Metabolic Defects, Muscle Strength, Cognitive Decline, and Body Composition: Implications for Healthy Aging. J Nutr. 2021 Dec 3;151(12):3606-3616. doi: 10.1093/jn/nxab309.

219. Kumar P, Liu C, Suliburk J, Hsu JW, Muthupillai R, Jahoor F, Minard CG, Taffet GE, Sekhar RV. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci. 2023 Jan 26;78(1):75-89. doi: 10.1093/gerona/glac135.

220. Pawar Poonam P, Ghorpade Hemant S., Kokane Bhavana A. Sublingual route for systemic drug delivery. Journal of Drug Delivery & Therapeutics. 2018; 8(6-s):340-343

221. Ahmad A, Akhtar J, Ahmad M, Wasim R, Khan MI. Drug Delivery Approaches for Buccal and Sublingual Administration. Drug Res (Stuttg). 2025 Apr 22. doi: 10.1055/a-2560-9884.

222. Bellanti, F.; Coda, A.R.D.; Trecca, M.I.; Lo Buglio, A.; Serviddio, G.; Vendemiale, G. Redox Imbalance in Inflammation: The Interplay of Oxidative and Reductive Stress. Antioxidants 2025, 14, 656. https://doi.org/10.3390/antiox14060656

223. Charbit, J.; Vidal, J.-S.; Hanon, O. Effects of Dietary Interventions on Cognitive Outcomes. Nutrients 2025, 17, 1964. https://doi.org/10.3390/nu17121964

224. Mini-Review Antiaging cognitivo 2025 https://www.mitochon.it/antiaging-cognitivo/?v=0d149b90e739