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Vitamin C, Aging and Alzheimer’s Disease
Open accessAbstract
Accumulating evidence in mice models of accelerated senescence indicates a rescuing role of ascorbic acid in premature aging. Supplementation of ascorbic acid appeared to halt cell growth, oxidative stress, telomere attrition, disorganization of chromatin, and excessive secretion of inflammatory factors, and extend lifespan. Interestingly, ascorbic acid (AA) was also found to positively modulate inflamm-aging and immunosenescence, two hallmarks of biological aging. Moreover, ascorbic acid has been shown to epigenetically regulate genome integrity and stability, indicating a key role of targeted nutrition in healthy aging. Growing in vivo evidence supports the role of ascorbic acid in ameliorating factors linked to Alzheimer’s disease (AD) pathogenesis, although evidence in humans yielded equivocal results. The neuroprotective role of ascorbic acid not only relies on the general free radical trapping, but also on the suppression of pro-inflammatory genes, mitigating neuroinflammation, on the chelation of iron, copper, and zinc, and on the suppression of amyloid-beta peptide (Aβ) fibrillogenesis. Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer's disease is rapidly increasing. Thus, dietary interventions, as a way to epigenetically modulate the human genome, may play a role in the prevention of AD. The present review is aimed at providing an up to date overview of the main biological mechanisms that are associated with ascorbic acid supplementation/bioavailability in the process of aging and Alzheimer’s disease. In addition, we will address new fields of research and future directions.
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“In the brain, AA has been increasingly found to promote several beneficial effects on neurodegeneration by direct neuroprotection against OS [116].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [116]
In the citing paper
“Vitamin C or ascorbic acid (AA) is a powerful antioxidant that can have beneficial effects on delaying the aging process and age-related diseases thorough its action on redox oxidative and mitochondrial pathways, on the immune system, on inflamm-aging, on endothelial integrity, and on lipoprotein metabolism [114,115,116,117,118,119,120,121].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [116]
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Cited by
Sorted by citations
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“Concerning vitamin C, MCI and AD patients present lower levels of ascorbic acid in plasma (138, 139).”
BackgroundMitochondrial mechanisms in Alzheimer’s disease: Quest for therapeutics
Kalani, K., Chaturvedi, P., Chaturvedi, P., Verma, V. K., Lal, N., Awasthi, S. K., & Kalani, A. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103547 · Cited by 28
Monnerat, J. A. D. S., de Souza, P. R., Cardoso, L. M. D. F., Mattos, J. D., Rocha, G. D. S., & Medeiros, R. F. (2020) · European Journal of Nutrition · doi:10.1007/s00394-020-02410-1 · Cited by 26
Optic Nerve Neuroprotection in Glaucoma: A Narrative Review
D’Angelo, A., Vitiello, L., Lixi, F., Abbinante, G., Coppola, A., Gagliardi, V., Pellegrino, A., & Giannaccare, G. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13082214 · Cited by 29
“Vitamin C is synthesized from glucose in the liver of many mammalian species; however, humans have evolutionarily lost this synthetic ability, making it necessary to obtain vitamin C through the diet [89], and fruits and vegetables are the main sources of vitamin C.”
BackgroundCsaba, G. (2018) · Acta Microbiologica et Immunologica Hungarica · doi:10.1556/030.65.2018.029 · Cited by 26
Ikeda, Y., Nagase, N., Tsuji, A., Kitagishi, Y., & Matsuda, S. (2021) · World Journal of Biological Chemistry · doi:10.4331/wjbc.v12.i6.104 · Cited by 25
Association between dietary vitamin C and telomere length: A cross-sectional study
Cai, Y., Zhong, Y.-D., Zhang, H., Lu, P.-L., Liang, Y., Hu, B., & Wu, H. M. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1025936 · Cited by 25
Differential roles of regulatory T cells in Alzheimer's disease
Jafarzadeh, A., Sheikhi, A., Jafarzadeh, Z., & Nemati, M. (2023) · Cellular Immunology · doi:10.1016/j.cellimm.2023.104778 · Cited by 26
The Antioxidant and Antiproliferative Activities of 1,2,3-Triazolyl-L-Ascorbic Acid Derivatives
Harej, A., Meščić, A., Stepanić, V., Klobučar, M., Pavelić, K., Pavelić, S. K., & Raić‐Malić, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194735 · Cited by 23
Nutrition: A non‐negligible factor in the pathogenesis and treatment of Alzheimer's disease
Wen, B., Han, X., Gong, J., Wang, P., Sun, W., Xu, C., Shan, A., Wang, X., Luan, H., Li, S., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14547 · Cited by 27
“127 Therefore,consideringtheundeniablerolesofvitaminsinantioxida-tion, anti-inflammation, and regulation of the gut microbiota, vitamins are a potential multi-target therapeutic approach for the prevention and treatment of AD.”
Ascorbate deficiency decreases dopamine release in gulo–/– and APP/PSEN1 mice
Consoli, D. C., Brady, L. J., Bowman, A. B., Calipari, E. S., & Harrison, F. E. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15151 · Cited by 23
Varshavi, D., Scott, F. H., Varshavi, D., Veeravalli, S., Phillips, I. R., Veselkov, K., Strittmatter, N., Takáts, Z., Shephard, E. A., & Everett, J. R. (2018) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2018.00028 · Cited by 23
“Ascorbate is known to be helpful in preventing or delaying the progression of ageing and age-related disease (Monacelli et al., 2017).”
BackgroundUna mirada actual de la vitamina C en salud y enfermedad
Villagrán, M., Muñoz-Roa, M., Díaz, F., Troncoso-Pantoja, C., Celis-Morales, C. A., & Mardones, L. (2019) · Revista chilena de nutrición · doi:10.4067/s0717-75182019000600800 · Cited by 22
Denniss, R. J., & Barker, L. A. (2023) · Behavioral Sciences · doi:10.3390/bs13050388 · Cited by 25
“Research has shown that increased vitamin C intake reduced oxidative stress and neuroinflammation in a mouse model of Alzheimer’s disease, slowing progression of the condition [90], and demonstrating its powerful antioxidant effects [89].”
BackgroundMaiuolo, J., Bosco, F., Guarnieri, L., Nucera, S., Ruga, S., Oppedisano, F., Tucci, L., Muscoli, C., Palma, E., Giuffrè, A. M., et al. (2023) · Plants · doi:10.3390/plants12112126 · Cited by 22
Role of functional food components in COVID-19 pandemic: A review
Hamid, H., Thakur, A., & Thakur, N. S. (2021) · Annals of Phytomedicine An International Journal · doi:10.21276/ap.covid19.2021.10.1.22 · Cited by 20
Targeted Mitochondrial Epigenetics: A New Direction in Alzheimer’s Disease Treatment
Song, Y., Zhu, X., Zhang, X.-M., & Xiong, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179703 · Cited by 21
“Traditional antioxidants such as vitamin C [98,99] and vitamin E (vit E) [100] have been used to study whether they have therapeutic effects on AD, but the results are not satisfactory.”
BackgroundShen, Y.-J., Huang, Y.-C., & Cheng, Y. (2024) · Antioxidants · doi:10.3390/antiox14010017 · Cited by 24
“Beyond its antioxidative properties, vitamin C has demonstrated neuroprotective and immunomodulatory effects in neurodegenerative diseases, further supporting its therapeutic potential [65–67].”
Zhang, Y., Peng, Y., Deng, W., Xiang, Q., Zhang, W., & Liu, M. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1371873 · Cited by 21
“Whereas, polyphenols and antioxidant vitamins were identified as associated with decreased oxidative stress and neuroinflammation (Monacelli et al., 2017).”
BackgroundDiet Associated with Inflammation and Alzheimer’s Disease
Vasefi, M., Hudson, M., & Ghaboolian-Zare, E. (2019) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-190152 · Cited by 21
“Vitamin C, or ascorbic acid, is theorized to hamper AD pathology and neurodegeneration by two main mechanisms: the modulation of oxidative stress and neuroinflammation [26, 30].”
BackgroundShiwakoti, S., Adhikari, D., Lee, J. P., Kang, K., Lee, I., Kim, H. J., & Oak, M. (2020) · Antioxidants · doi:10.3390/antiox9121243 · Cited by 20
“Various antioxidants, such as ascorbic acid and N-acetylcysteine, have shown a significant role in delaying age-related endothelial dysfunction [51,52].”
BackgroundVenkataraman, A., Kordic, I., Li, J., Zhang, N. Y., Bharadwaj, N. S., Fang, Z., Das, S., & Coskun, A. F. (2024) · npj Aging · doi:10.1038/s41514-024-00178-w · Cited by 21
Future foods, dietary factors and healthspan
Li, K., Wang, C., Wang, Y., Fu, L., & Zhang, N. (2023) · Journal of Future Foods · doi:10.1016/j.jfutfo.2022.12.001 · Cited by 20
Marchi, F. D., Vignaroli, F., Mazzini, L., Comi, C., & Tondo, G. (2023) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527322666230608110201 · Cited by 19
Wang, Y., Huang, Y., Ma, A., You, J., Miao, J., & Li, J. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c01323 · Cited by 21
Mitochondrial Dysfunction as a Key Event during Aging: From Synaptic Failure to Memory Loss
Jara, C., Torres, A. K., Olesen, M. A., & Tapia‐Rojas, C. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.88445 · Cited by 20
Unraveling the Vicious Cycle: Oxidative Stress and Neurotoxicity in Neurodegenerative Diseases
Wang, X., Dong, B., Gan, Q., Li, J., Wu, P., Guan, Y., & Wang, J. (2025) · FASEB BioAdvances · doi:10.1096/fba.2025-00093 · Cited by 24
Portugal, C. C. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.12.040 · Cited by 18
Ferroptosis and Alzheimer’s: unveiling new avenues for the treatment and prevention
Sharma, V., Sharma, P., & Singh, T. G. (2025) · Metabolic Brain Disease · doi:10.1007/s11011-025-01587-w · Cited by 18
“In the 5X-FAD mouse model, treatment with high doses of ascorbic acid decreases the formation of Aβ plaque (Monacelli et al. 2017).”
Do natural antioxidants play a role in Alzheimer's disease?
Lange, K. W., Lange, K. M., Nakamura, Y., & Li, S. (2020) · Journal of Food Bioactives · doi:10.31665/jfb.2020.11233 · Cited by 17
Ganeshkumar, A., Suvaithenamudhan, S., & Rajaram, R. (2020) · Current Microbiology · doi:10.1007/s00284-020-02269-9 · Cited by 17
Han, Z., Zhang, Z., Guan, Y., Chen, B., Yu, M., Zhang, L., Fang, J., Gao, Y., & Guo, Z. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.01.120 · Cited by 18
Tolédano, A., Rodríguez‐Casado, A., Álvarez, M., & Toledano‐Díaz, A. (2024) · Brain Sciences · doi:10.3390/brainsci14111101 · Cited by 19
Abd-Allah, H., Nasr, M., Ahmed-Farid, O. A.-H., El‐Marasy, S. A., Bakeer, R. M., & Ahmed, R. F. (2021) · ACS Omega · doi:10.1021/acsomega.0c05096 · Cited by 16
Effect of antioxidant intake patterns on risks of dementia and cognitive decline
Zhou, F., Xie, X., Zhang, H., & Liu, T. (2022) · European Geriatric Medicine · doi:10.1007/s41999-022-00720-7 · Cited by 17
Molecular Pharmacology of Vitamin C and Relevance to Health and Obesity—A Narrative Review
Wilson, R. B., Liang, Y., Kaushal, D., & Carr, A. C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147523 · Cited by 16
“SVCT-1 and SVCT-2 expression decreases with age, which impairs the absorption and distribution of vitamin C in the body in older persons [47–49].”
Background
Metadata
- Authors
- Monacelli, F., Acquarone, E., Giannotti, C., Borghi, R., & Nencioni, A.
- Affiliations
- University of Genoa (IT)
- Corresponding author
- Monacelli, Fiammetta
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2017-06-27
- Volume
- 9
- Issue
- 7
- Pages
- 670
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC5537785
- OpenAlex
- W2724874603
- Cited by
- 243
- References
- 148
- Citations by year
- 2026: 9 · 2025: 29 · 2024: 37 · 2023: 31 · 2022: 38 · 2021: 34 · 2020: 27 · 2019: 22 · 2018: 14 · 2017: 2
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion, other-oa)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- vitamin C, aging, Alzheimer's disease, accelerated senescence, inflammaging, immunosenescence, telomere shortening, oxidative stress, epigenetic regulation, neuroinflammation, dietary supplementation, lifespan extension, healthy aging
- MeSH terms
- Aging, Alzheimer Disease, Animals, Ascorbic Acid, Brain, Disease Models, Animal, Humans, Vascular Diseases, Randomized Controlled Trials as Topic, Oxidative Stress, Nutrigenomics, Epigenomics, Plaque, Amyloid, Observational Studies as Topic
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