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, ascorbic acid promotes beneficial effects on neurodegeneration by direct neuroprotection against OS.
“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]
Vitamin C (ascorbic acid) is a powerful antioxidant that can have beneficial effects on delaying the aging process and age-related diseases through its action on redox oxidative and mitochondrial pathways, immune system, inflamm-aging, endothelial integrity, and lipoprotein metabolism.
“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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Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358 · cited 1× · see citing works
“Inflamm-aging may be considered a biological background for both the aging process and the pathophysiological process of frailty in humans [7].”
BackgroundMetals, Toxicity and Oxidative Stress
Valko, M., Morris, H., & Cronin, M. (2005) · Current Medicinal Chemistry · doi:10.2174/0929867053764635 · Cited by 5,018 · cited 1× · see citing works
“Interestingly, some in vitro studies investigated the pro-oxidant properties of ascorbate [109], which were mainly attributed to the release of metal ions from damaged cells.”
BackgroundChronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
Franceschi, C., & Campisi, J. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu057 · Cited by 3,891 · cited 1× · see citing works
“The free radical theory of aging allows an explanation of the molecular mechanisms underlying the aging process, at least partially, and the pathogenesis of age-related diseases, such as atherosclerosis, cardiovascular diseases, dementia, diabetes, and osteoporosis [3,4].”
BackgroundBloom (2014) · doi:10.1001/jamaneurol.2013.5847 · Cited by 2,194 · cited 1× · see citing works
“Extracellular amyloid plaques are also responsible for the hyperphosphorylation of the cytoskeletal Tau protein [67].”
BackgroundVitamin C as an Antioxidant: Evaluation of Its Role in Disease Prevention
Padayatty, S. J., Katz, A., Wang, Y., Eck, P., Kwon, O., Lee, J.-H., Chen, S., Corpe, C., Dutta, A., Dutta, S. K., et al. (2003) · Journal of the American College of Nutrition · doi:10.1080/07315724.2003.10719272 · Cited by 1,949 · cited 2× · see citing works
“The increasing burden of this life-threatening condition [60] and the lack of disease-modifying drugs have guided the research towards preventive strategies, targeting AD modifiable risk factors [12].”
BackgroundOxidative Stress, Prooxidants, and Antioxidants: The Interplay
Rahal, A., Kumar, A., Singh, V., Yadav, B., Tiwari, R., Chakraborty, S., & Dhama, K. (2014) · BioMed Research International · doi:10.1155/2014/761264 · Cited by 1,730 · cited 1× · see citing works
“A pro-oxidant or antioxidant effect of AA mainly relies on the concentration gradient and redox state of a cell [106].”
BackgroundProinflammatory Cytokines, Aging, and Age-Related Diseases
Michaud, M., Balardy, L., Moulis, G., Gaudin, C., Peyrot, C., Vellas, B., Cesari, M., & Nourhashemi, F. (2013) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2013.05.009 · Cited by 1,094 · cited 2× · see citing works
“mechanisms are responsible for altered T cell expression and the altered phenotype of immunological subpopulations [6].”
BackgroundDietary Intake of Antioxidants and Risk of Alzheimer Disease
Engelhart, M. J. (2002) · JAMA · doi:10.1001/jama.287.24.3223 · Cited by 1,080 · cited 1× · see citing works
“The Rotterdam study showed the most consistent association between higher AA intake and reduced relative risk for AD in the largest population study [140] with the higher magnitude of association in people most depleted of AA (e.”
BackgroundMetals, oxidative stress and neurodegenerative disorders
Jomová, K., Vondráková, D., Lawson, M. K., & Valko, M. (2010) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-010-0563-x · Cited by 1,053 · cited 4× · see citing works
“AA repressed telomere shortening, decreased the production of pro-inflammatory cytokines, such as IL-6 and IL-8, downregulated the expression of markers of aging, such as cyclin-dependent kinase inhibitor 2A, multiple tumor suppressor 1 p16Ink4a and zinc finger transcriptional GATA4, and repressed the SASP (elevated s…”
BackgroundInfluentialIschiropoulos, H. (1998) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1998.0755 · Cited by 1,024 · cited 1× · see citing works
“The conjugated aromatic ring of tyrosine residues is also a target for free-radical attack, and accumulation of dityrosine and 3-nitrotyrosine has also been reported in the AD brain [77].”
BackgroundDoes vitamin C act as a pro‐oxidant under physiological conditions?
Carr, A. C., & Frei, B. B. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.9.1007 · Cited by 883 · cited 1× · see citing works
“A previous study undermined the protective role of AA in dementia, indicating that the interaction of AA with ‘free’ catalytically-active metal ions could contribute to oxidative damage through the production of hydroxyl and alkoxyl radicals [108].”
BackgroundVitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells
Blaschke, K., Ebata, K. T., Karimi, M. M., Zepeda-Martínez, J. A., Goyal, P., Mahapatra, S., Tam, A., Laird, D. J., Hirst, M., Rao, A., et al. (2013) · Nature · doi:10.1038/nature12362 · Cited by 865 · cited 1× · see citing works
“Finally, the field of epigenetics has recently answered the question as to why AA is disproportionally concentrated in CSF and brain parenchyma compared to plasma [28].”
BackgroundAscorbate regulation and its neuroprotective role in the brain
Rice, M. E. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01543-x · Cited by 835 · cited 1× · see citing works
“AA, at millimolar concentrations, was able to scavenge the superoxide anion, recycling the α-tocopherol within the lipid layers of the cellular membrane [54].”
BackgroundVitamin C in Human Health and Disease Is Still a Mystery? An Overview
Naidu, K. A. (2003) · Nutrition Journal · doi:10.1186/1475-2891-2-7 · Cited by 810 · see citing works
Vitamin C function in the brain: Vital role of the ascorbate transporter SVCT2
Harrison, F. E., & May, J. M. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.12.018 · Cited by 661 · cited 2× · see citing works
“Cerebrospinal fluid (CSF) ascorbic acid concentrations (200–400 mM) are higher compared to those in cerebral parenchyma and in plasma (30–60 nM) [43].”
BackgroundA Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans
Yang, W., & Hekimi, S. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000556 · Cited by 630 · cited 1× · see citing works
“These notions have recently been challenged by findings in model organisms that show beneficial effects on lifespan of increased ROS generation produced by mutations or pro-oxidant treatments [46,47].”
Yin, R., Mao, S.-Q., Zhao, B., Chong, Z., Yang, Y., Zhao, C., Zhang, D., Huang, H., Gao, J., Li, Z., et al. (2013) · Journal of the American Chemical Society · doi:10.1021/ja4028346 · Cited by 609 · cited 2× · see citing works
“Namely, the oxidation of 5-mc (5-methylcytosine) to 5-hmc (5-hydroxymethylcytosine), as part of dynamic DNA demethylation, is catalyzed by TET (ten-eleven translocation) dioxygenase enzymes, for which AA is a critical co-factor [23,145].”
BackgroundButterfield, D. A., Reed, T., Newman, S. F., & Sultana, R. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.05.037 · Cited by 564 · see citing works
Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease
Rinaldi, P., Polidori, M. C., Metastasio, A., Mariani, E., Mattioli, P., Cherubini, A., Catani, M., Cecchetti, R., Senin, U., & Mecocci, P. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(03)00031-9 · Cited by 562 · cited 1× · see citing works
“However, plasma levels of AA were found to be lower both in patients with mild cognitive impairment and AD, compared to controls [136].”
Vitamin C in Disease Prevention and Cure: An Overview
Chambial, S., Dwivedi, S., Shukla, K. K., John, P. J., & Sharma, P. (2013) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-013-0375-3 · Cited by 551 · cited 1× · see citing works
“It is well known that at higher concentrations, AA acts as a pro-oxidant, either by generating reactive oxygen species or by inhibiting the antioxidant systems in the presence of iron, which, in turn, induces lipid peroxidation [105].”
BackgroundDeane, R., Bell, R. D., Sagare, A. P., & Zloković, B. V. (2009) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152709787601867 · Cited by 549 · see citing works
RAGE, LRP-1, and amyloid-beta protein in Alzheimer’s disease
Donahue, J. E., Flaherty, S. L., Johanson, C. E., Duncan, J. A., Silverberg, G. D., Miller, M. C., Tavares, R., Yang, W., Wu, Q., Sabo, E., et al. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0115-3 · Cited by 519 · cited 1× · see citing works
“In patients with AD, brain endothelial LRP-1 expression throughout the BBB is reduced [125].”
BackgroundInflammatory networks in ageing, age-related diseases and longevity
Vasto, S., Candore, G., Balistreri, C. R., Caruso, M., Colonna‐Romano, G., Grimaldi, M. P., Listı̀, F., Nuzzo, D., Lio, D., & Caruso, C. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.015 · Cited by 481 · cited 1× · see citing works
“The free radical theory of aging allows an explanation of the molecular mechanisms underlying the aging process, at least partially, and the pathogenesis of age-related diseases, such as atherosclerosis, cardiovascular diseases, dementia, diabetes, and osteoporosis [3,4].”
BackgroundAssociation Between Nutritional Status and Cognitive Functioning in a Healthy Elderly Population
Goodwin, J. S. (1983) · JAMA · doi:10.1001/jama.1983.03330450047024 · Cited by 481 · see citing works
The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy
McGeer, P. L., & McGeer, E. G. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1177-7 · Cited by 467 · cited 1× · see citing works
“The amyloid cascade hypothesis is considered the primary event of AD pathogenesis [63].”
BackgroundHeller, R., Unbehaun, A., Schellenberg, B., Mayer, B., Werner‐Felmayer, G., & Werner, E. R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m004392200 · Cited by 421 · cited 2× · see citing works
“In addition, AA was found to play a role in the function of endothelial nitric oxide synthase (eNOS) by recycling the eNOS co-factor, tetrahydrobiopterin, which is relevant for arterial elasticity and blood pressure regulation [18].”
BackgroundMinor, E. A., Court, B. L., Young, J. I., & Wang, G. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.c113.464800 · Cited by 413 · cited 1× · see citing works
“Namely, the oxidation of 5-mc (5-methylcytosine) to 5-hmc (5-hydroxymethylcytosine), as part of dynamic DNA demethylation, is catalyzed by TET (ten-eleven translocation) dioxygenase enzymes, for which AA is a critical co-factor [23,145].”
BackgroundAntioxidant Therapies for Alzheimer's Disease
Feng, Y., & Wang, X. (2012) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2012/472932 · Cited by 382 · cited 1× · see citing works
“Over the years, L-ascorbic acid (AA) has been increasingly found to promote several beneficial effects on neurodegeneration, with particular regard to Alzheimer’s disease (AD) [59].”
BackgroundDuarte, T. L., & Lunec, J. (2005) · Free Radical Research · doi:10.1080/10715760500104025 · Cited by 374 · see citing works
Role of Vitamin C in the Function of the Vascular Endothelium
May, J. M., & Harrison, F. E. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5205 · Cited by 358 · see citing works
Expression of heme oxygenase‐1 in the senescent and alzheimer‐diseased brain
Schipper, H. M., Cissé, S., & Stopa, E. G. (1995) · Annals of Neurology · doi:10.1002/ana.410370609 · Cited by 353 · cited 1× · see citing works
“In AD hippocampal neurons and astrocytes, a redox imbalance has been observed with an overexpression of heme oxygenase-1 and increased levels of Cu/Zn superoxide dismutase [76].”
BackgroundSuperoxide dismutase is dispensable for normal animal lifespan
Raamsdonk, J. M. V., & Hekimi, S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116158109 · Cited by 334 · cited 1× · see citing works
“These notions have recently been challenged by findings in model organisms that show beneficial effects on lifespan of increased ROS generation produced by mutations or pro-oxidant treatments [46,47].”
BackgroundVitamin E and Vitamin C Supplement Use and Risk of Incident Alzheimer Disease
Morris, M. C., Beckett, L. A., Scherr, P. A., Hebert, L. E., Bennett, D. A., Field, T. S., & Evans, D. A. (1998) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199809000-00001 · Cited by 332 · cited 1× · see citing works
“According to the CHAP study [137], none of the elderly dementia-free participants longitudinally developed dementia, due to AA supplementation.”
MethodBloom, D. E. (2011) · Science · doi:10.1126/science.1209290 · Cited by 327 · see citing works
Regulation of the epigenome by vitamin C
Young, J. I., Züchner, S., & Wang, G. (2015) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071714-034228 · Cited by 319 · cited 1× · see citing works
“Namely, AA induced a significant demethylation of 5-methylcytosine (5mC) to 5-hydroxymethyl cytosine (5hmC) [22,23].”
BackgroundCevenini, E., Monti, D., & Franceschi, C. (2013) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0b013e32835ada13 · Cited by 317 · see citing works
Oxidative stress, inflamm-aging and immunosenescence
Cannizzo, E. S., Clement, C. C., Sahu, R. K., Follo, C., & Santambrogio, L. (2011) · Journal of Proteomics · doi:10.1016/j.jprot.2011.06.005 · Cited by 303 · cited 2× · see citing works
“Prolonged exposure to antigens throughout life produces a progressive modification of the individual homeostasis [2].”
BackgroundBlood–brain barrier impairment in Alzheimer disease
Bowman, G. L., Kaye, J. A., Moore, M., Waichunas, D., Carlson, N. E., & Quinn, J. F. (2007) · Neurology · doi:10.1212/01.wnl.0000262031.18018.1a · Cited by 294 · see citing works
Effects of Vitamin C on health: a review of evidence
Bei, R. (2013) · Frontiers in bioscience · doi:10.2741/4160 · Cited by 259 · cited 5× · see citing works
“In addition, in the CNS, AA participated in several hydroxylation reactions that include the redox activity of Fe3+ and Cu2+ at dioxigenase sites.”
BackgroundInfluentialOxidative stress and frailty: A systematic review and synthesis of the best evidence
Soysal, P., Isik, A. T., Carvalho, A. F., Fernandes, B. S., Solmi, M., Schofield, P., Veronese, N., & Stubbs, B. (2017) · Maturitas · doi:10.1016/j.maturitas.2017.01.006 · Cited by 252 · cited 1× · see citing works
“Recently, it has been shown that elderly people with lower peripheral antioxidant parameters, including AA and a decreased antioxidant capacity, are more prone to clinical vulnerability, disability, frailty and higher mortality over a 5-year follow up [50].”
BackgroundDringen, R., Kußmaul, L., Gutterer, J. M., Hirrlinger, J., & Hamprecht, B. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0722523.x · Cited by 243 · cited 1× · see citing works
“The astrocyte-neuron interaction was found to function as an essential mechanism for AA recycling, participating in the anti- oxidative defense of the brain [97].”
BackgroundOxidative Stress, Inflammaging, and Immunosenescence
Bauer, M. E., & la Fuente, M. D. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-397803-5.00004-6 · Cited by 229 · see citing works
The epigenetic role of vitamin C in health and disease
Camarena, V., & Wang, G. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2145-x · Cited by 223 · cited 1× · see citing works
“In the last decades, the understanding of AA properties has undergone a major revolution, ranging from a simple antioxidant to a micronutrient, capable of epigenetic regulation [20,21].”
BackgroundAntioxidant Activity of Vitamin C in Iron-overloaded Human Plasma
Berger, T. M., Polidori, M. C., Dabbagh, A. J., Evans, P., Halliwell, B. B., Morrow, J. D., Roberts, L. J., & Frei, B. B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.25.15656 · Cited by 208 · cited 1× · see citing works
“However, to complicate the issue, AA was observed to reduce in vivo oxidative damage in the presence of iron, despite its well-known in vitro pro-oxidant properties in buffer systems containing iron [83].”
BackgroundVitamin C and genomic stability
Halliwell, B. B. (2001) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(01)00072-0 · Cited by 201 · cited 1× · see citing works
“In the last decades, the understanding of AA properties has undergone a major revolution, ranging from a simple antioxidant to a micronutrient, capable of epigenetic regulation [20,21].”
BackgroundHippocampal RAGE immunoreactivity in early and advanced Alzheimer’s disease
Miller, M. C., Tavares, R., Johanson, C. E., Hovanesian, V., Donahue, J. E., Gonzalez, L., Silverberg, G. D., & Stopa, E. G. (2008) · Brain Research · doi:10.1016/j.brainres.2008.06.124 · Cited by 194 · see citing works
vel Szic, K. S., Declerck, K., Vidaković, M., & Vanden Berghe, W. (2015) · Clinical Epigenetics · doi:10.1186/s13148-015-0068-2 · Cited by 192 · cited 1× · see citing works
“The endogenous antioxidant enzymatic defense system superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH) counteracts oxidative exogenous agents from diet and may undergo substantial decrease related to the aging process [8].”
BackgroundHarrison, F. E. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111853 · Cited by 191 · cited 1× · see citing works
“[143], the classification of groups according to AA status differs greatly among studies.”
BackgroundShearer, J., & Szalai, V. A. (2008) · Journal of the American Chemical Society · doi:10.1021/ja805940m · Cited by 189 · cited 1× · see citing works
“It has been reported that neurotoxic forms of amyloid β, Aβ (1–42), Aβ (1–40), and also Aβ (25–35) induced copper-mediated oxidation of ascorbate, whereas non-toxic Aβ (40–1) did not [110,111].”
BackgroundVitamin C transport and its role in the central nervous system
May, J. M. (2012) · Subcellular Biochemistry · doi:10.1007/978-94-007-2199-9_6 · Cited by 186 · cited 1× · see citing works
“In turn, the direct contact of activated glial cells with neurons may generate immune mediators (nitric oxide, ROS, pro-inflammatory cytokines, and chemokines) that are neurotoxins, spreading inflammation in the central nervous system [78,79].”
BackgroundScuteri, A., Tesauro, M., Appolloni, S., Preziosi, F., Brancati, A. M., & Volpe, M. (2007) · Journal of Hypertension · doi:10.1097/hjh.0b013e3280895b55 · Cited by 181 · cited 2× · see citing works
“The risk of either AD or vascular dementia is higher in patients with elevated blood pressure, which suggests how arterial stiffness and atherosclerosis play important pathogenetic roles [123].”
BackgroundApelt, J., Bigl, M., Wunderlich, P., & Schliebs, R. (2004) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2004.07.006 · Cited by 175 · cited 1× · see citing works
“Brain accumulation of Aβ1-42 oligomers results in increased neuronal vulnerability to oxidative stress [64,65] neuroinflammation with impairment of synaptic plasticity [66], and neuronal death.”
BackgroundNeufcourt, L., Assmann, K. E., Fezeu, L., Touvier, M., Graffouillère, L., Shivappa, N., Hébert, J. R., Wirth, M. D., Herçberg, S., Galan, P., et al. (2015) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2015.09.002 · Cited by 157 · see citing works
Alzheimer's Disease: A Lesson from Mitochondrial Dysfunction
Moreira, P. I., Santos, M. S., & Oliveira, C. R. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1703 · Cited by 150 · cited 1× · see citing works
“In addition, Aβ oligomers interfere with mitochondrial dynamics [68,69].”
BackgroundMa, T., Hoeffer, C. A., Wong, H., Massaad, C. A., Zhou, P., Iadecola, C., Murphy, M. P., Pautler, R. G., & Klann, E. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6566-10.2011 · Cited by 146 · cited 1× · see citing works
“Brain accumulation of Aβ1-42 oligomers results in increased neuronal vulnerability to oxidative stress [64,65] neuroinflammation with impairment of synaptic plasticity [66], and neuronal death.”
BackgroundRosales‐Corral, S., Tan, D. X., Reiter, R. J., Valdivia‐Velázquez, M., Martínez‐Barboza, G., Acosta‐Martínez, J. P., & Ortíz, G. G. (2003) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2003.00057.x · Cited by 143 · cited 1× · see citing works
“In rat hippocampal brains, oral administration of AA reduced oxidative stress and neuroinflammation mediated by Aβ fibrils [100].”
BackgroundDede, D. S., Yavuz, B., Yavuz, B. B., Cankurtaran, M., Halil, M., Ulger, Z., Cankurtaran, E. S., Aytemir, K., Kabakci, G., & Ariogul, S. (2007) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01378.x · Cited by 142 · cited 1× · see citing works
“AA was reported to reverse the generation and metabolism of NO [94], and to prevent endothelial dysfunction by inhibiting LDL oxidation.”
BackgroundOld Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders
Covarrubias‐Pinto, A., Acuña, A. I., Beltrán, F. A., Torres-Díaz, L., & Castro, M. A. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161226095 · Cited by 140 · cited 2× · see citing works
“Imbalance of AA homeostasis has been extensively demonstrated in neurodegeneration [58].”
BackgroundPolidori, M. C., & Mecocci, P. (2002) · Journal of Alzheimer s Disease · doi:10.3233/jad-2002-4608 · Cited by 137 · cited 1× · see citing works
“With respect to lipid peroxidation products, oxidized proteins, and DNA damage, peroxynitrites have been increasingly detected in the AD temporal cortex, as well as oxidation of mitochondrial DNA and nuclear DNA in the parietal cortex [75].”
BackgroundDixit, S., Bernardo, A., Walker, J. M., Kennard, J. A., Kim, G. Y., Kessler, E. S., & Harrison, F. E. (2015) · ACS Chemical Neuroscience · doi:10.1021/cn500308h · Cited by 135 · cited 2× · see citing works
“APP/PSEN 1 mice lacking the SVCT2 transporter and having AA mild deficiency showed accelerated amyloid pathogenesis, linked to oxidative stress pathways, compared to control mice with normal brain ascorbic acid [81].”
BackgroundQiu, S., Li, L., Weeber, E. J., & May, J. M. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21204 · Cited by 133 · cited 2× · see citing works
“Using SVTC knockout mice as an in vivo model showed that AA, at lower doses, was able to mediate dendrite formation, increasing post-synaptic electrical potential [56].”
BackgroundMethodScorza, G., Pietraforte, D., & Minetti, M. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00378-4 · Cited by 132 · cited 1× · see citing works
“AA also favored the restoration of NO metabolism from S-nitrosothiols in plasma [127], reducing nitrite (NO2) to NO, which may preserve NO in tissues or plasma.”
BackgroundSantoro, A., Pini, E., Scurti, M., Palmas, M. G., Berendsen, A. A. M., Brzozowska, A., Pietruszka, B., Szczecińska, A., Cano, N., Meunier, N., et al. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.12.001 · Cited by 129 · see citing works
Copper, β-amyloid, and Alzheimer's disease: Tapping a sensitive connection
Bush, A. I., Masters, C. L., & Tanzi, R. E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2135061100 · Cited by 128 · see citing works
Kook, S.-Y., Lee, K.-M., Kim, Y., Cha, M.-Y., Kang, S., Baik, S., Lee, H., Park, R., & Mook‐Jung, I. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.26 · Cited by 127 · cited 1× · see citing works
“The higher supplementation of AA in KO-Tg mice resulted in the amelioration of BBB disruption and mitochondrial alteration, with substantial reduction of amyloid plaque burden [114].”
BackgroundNadal, R. C., Rigby, S. E. J., & Viles, J. H. (2008) · Biochemistry · doi:10.1021/bi8011093 · Cited by 118 · cited 1× · see citing works
“of Fenton-Haber Weiss reactions of ascorbate and Cu2+, rapidly quenching harmful radicals [112].”
BackgroundVitamin C restores healthy aging in a mouse model for Werner syndrome
Massip, L., Garand, C., Paquet, É. R., Cogger, V. C., O'Reilly, J. N., Tworek, L., Hatherell, A., Taylor, C. G., Thorin, É., Zahradka, P. C., et al. (2009) · The FASEB Journal · doi:10.1096/fj.09-137133 · Cited by 114 · cited 1× · see citing works
“It is noteworthy that in healthy mice, the beneficial effects of AA on health and lifespan were not significant and the supplementation significantly reduced the oxidative damage only in Wrn∆hel/∆hel mouse liver [30,34].”
BackgroundDementia and Alzheimer's Disease in Community-Dwelling Elders Taking Vitamin C and/or Vitamin E
Fillenbaum, G. G., Kuchibhatla, M. N., Hanlon, J. T., Artz, M. B., Pieper, C. F., Schmader, K. E., Dysken, M. W., & Gray, S. L. (2005) · Annals of Pharmacotherapy · doi:10.1345/aph.1g280 · Cited by 113 · cited 1× · see citing works
“In a population study of North Carolina, 616 elders aged over 75 years and long-term supplement users of AA did not show any neuroprotection against developing AD [142].”
BackgroundChan, S., Kantham, S., Rao, V. M., Palanivelu, M. K., Pham, H. L., Shaw, P. N., McGeary, R. P., & Ross, B. P. (2015) · Food Chemistry · doi:10.1016/j.foodchem.2015.11.118 · Cited by 113 · cited 1× · see citing works
“In addition, a recent report evaluated the in vitro effects of different food constituents on brain metal chelation, oxidative stress, and fibrillogenesis [89].”
BackgroundSultana, R., Mecocci, P., Mangialasche, F., Cecchetti, R., Baglioni, M., & Butterfield, D. A. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-101425 · Cited by 111 · cited 1× · see citing works
“Oxidative stress interacts with multiple features associated with AD pathogenesis, such as APP processing, mitochondrial dysfunction, and metal accumulation [80].”
BackgroundDikalov, S., Vitek, M. P., & Mason, R. P. (2003) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2003.11.004 · Cited by 109 · see citing works
Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain
Emir, U. E., Raatz, S. K., McPherson, S. E., Hodges, J. S., Torkelson, C. J., Tawfik, P. N., White, T. J. H., & Terpstra, M. (2011) · NMR in Biomedicine · doi:10.1002/nbm.1646 · Cited by 109 · cited 2× · see citing works
“With testing by neuroimaging, recent research has demonstrated that it is possible to detect brain levels of AA by using a MEGA-PRESS mediated spectra (MEGA-PRESS, MEGA-point-resolved spectroscopy) [144].”
BackgroundMethodMurakami, K., Murata, N., Ozawa, Y., Kinoshita, N., Irie, K., Shirasawa, T., & Shimizu, T. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101971 · Cited by 108 · cited 1× · see citing works
“[91], in APP transgenic mice, showed that AA administration attenuated oligomerization, but not the total amyloid plaque volume.”
BackgroundAllen, C., & Bayraktutan, U. (2009) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2008.00987.x · Cited by 105 · cited 1× · see citing works
“Moreover, an in vitro study provided evidence that AA reversed hyperglycemia-mediated BBB disruption [130].”
BackgroundHarrison, F. E., Hosseini, A. H., McDonald, M. P., & May, J. M. (2009) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2009.06.006 · Cited by 103 · cited 1× · see citing works
“A previous study in APP/PSEN 1 transgenic mice showed that parenteral administration of AA possessed nootropic properties, without altering the AD-like features of plaque deposition, oxidative stress and acetylcholinesterase activity [85].”
Background“Inflamm‐aging” influences immune cell survival factors in human bone marrow
Pangrazzi, L., Meryk, A., Naismith, E., Kozieł, R., Lair, J., Krismer, M., Trieb, K., & Grubeck‐Loebenstein, B. (2016) · European Journal of Immunology · doi:10.1002/eji.201646570 · Cited by 100 · cited 1× · see citing works
“This study is of key relevance in assessing the protective role for AA in immunosenescence [35].”
Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline
Harrison, F. E., Bowman, G. L., & Polidori, M. C. (2014) · Nutrients · doi:10.3390/nu6041752 · Cited by 99 · cited 6× · see citing works
“The lack of accuracy in study designs and methodologies may also affect the reliability of the findings [57].”
BackgroundInfluentialDesjardins, D., Cacho‐Valadez, B., Liu, J., Wang, Y., Yee, C. S., Bernard, K., Khaki, A., Breton, L., & Hekimi, S. (2016) · Aging Cell · doi:10.1111/acel.12528 · Cited by 94 · cited 1× · see citing works
“In particular, in a Caenorhabdilis elegans model, [48] AA displayed an inverted U-shaped dose–response relationship between ROS levels and lifespan; both high and low levels of ROS were detrimental for longevity.”
BackgroundYao, Y., Chinnici, C. M., Tang, H., Trojanowski, J. Q., Lee, V. M. ‐., & Praticò, D. (2004) · Journal of Neuroinflammation · doi:10.1186/1742-2094-1-21 · Cited by 90 · see citing works
Maillard Degradation Pathways of Vitamin C
Smuda, M., & Glomb, M. A. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201300399 · Cited by 87 · cited 1× · see citing works
“In addition, it has been recently documented that 75% of ascorbic acid degradation is due to Maillard degradation pathways (amide-AGEs) [146].”
BackgroundThe Haptoglobin 2-2 Phenotype Affects Serum Markers of Iron Status in Healthy Males
Langlois, M. R., Martin, M., Boelaert, J. R., Beaumont, C., Taes, Y., Buyzere, M. D., Bernard, D. R., Neels, H. M., & Delanghe, J. (2000) · Clinical Chemistry · doi:10.1093/clinchem/46.10.1619 · Cited by 85 · see citing works
Vitamin C Transporters, Recycling and the Bystander Effect in the Nervous System: SVCT2 versus Gluts
Nualart, F. (2014) · Journal of Stem Cell Research & Therapy · doi:10.4172/2157-7633.1000209 · Cited by 85 · cited 4× · see citing works
“This bystander effect is responsible for AA recycling activity between neurons and astrocytes and plays a role in the fine balance between pro-oxidative and anti-oxidative status [53].”
BackgroundInfluentialJiang, D., Li, X., Liu, L., Yagnik, G. B., & Zhou, F. (2010) · The Journal of Physical Chemistry B · doi:10.1021/jp9095375 · Cited by 83 · cited 2× · see citing works
“Moreover, reaction rates and mechanisms of AA oxidation resulted in greater biological relevance in the presence of Cu(II)-containing Aβ oligomers and fibrils, given the close proximity of ROS to cell membranes [104].”
BackgroundThe Association of Antioxidants and Cognition in the Nurses' Health Study
Devore, E. E., Kang, J. H., Stampfer, M. J., & Grodstein, F. (2012) · American Journal of Epidemiology · doi:10.1093/aje/kws202 · Cited by 83 · cited 1× · see citing works
“Another large population study has shown a protective role for AA in vascular dementia and cognitively-intact subjects, but no protective role of AA was shown for Alzheimer’s disease [139].”
BackgroundBerendsen, A., Santoro, A., Pini, E., Cevenini, E., Ostan, R., Pietruszka, B., Rolf, K., Cano, N., Caille, A., Lyon-Belgy, N., et al. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.10.002 · Cited by 82 · see citing works
The Possible Role of Antioxidant Vitamin C in Alzheimer’s Disease Treatment and Prevention
Heo, J., Lee, H., & Lee, K. (2013) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317512473193 · Cited by 79 · cited 2× · see citing works
“Therefore, several in vitro and in vivo studies underpin the therapeutic role of AA in AD, bolstering oxidative defense [99].”
BackgroundVitamin C alleviates aging defects in a stem cell model for Werner syndrome
Li, Y., Zhang, W., Chang, L., Han, Y., Sun, L., Gong, X., Tang, H., Liu, Z., Deng, H., Ye, Y., et al. (2016) · Protein & Cell · doi:10.1007/s13238-016-0278-1 · Cited by 78 · cited 1× · see citing works
“The positive effects of AA on premature cellular events was confirmed by treatment with AA on Werner’s syndrome protein (WRN-deficient) human mesenchymal stem cells (MSCs) [33].”
BackgroundAscorbic Acid and Rates of Cognitive Decline in Alzheimer's Disease
Bowman, G. L., Dodge, H. H., Frei, B. B., Calabrese, C., Oken, B., Kaye, J. A., & Quinn, J. F. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-0923 · Cited by 78 · see citing works
Cheng, R., Lin, B., Lee, K., & ORTWERTH, B. J. (2001) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(01)00051-5 · Cited by 78 · cited 1× · see citing works
“Evidence from a mouse model that selectively over-expressed the AA transporter SVCT2 in the eye [107] implicated AA in age-related damage to crystalline proteins in the lens.”
BackgroundA Review of the Major Vascular Risk Factors Related to Alzheimer's Disease
Polidori, M. C., Pientka, L., & Mecocci, P. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120871 · Cited by 77 · cited 1× · see citing works
“The efficacy of AA against BBB breakdown due to cortical compression was reported [90].”
BackgroundAscorbate‐induced differentiation of embryonic cortical precursors into neurons and astrocytes
Lee, J., Chang, M., Park, C., Kim, H., Kim, J., Son, H., Lee, Y., & Lee, S. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10647 · Cited by 77 · cited 1× · see citing works
“[55] further demonstrated that AA (at a 200 millimolar concentration) was effective in differentiating neuronal and astrocytes precursors, promoting synaptic maturation.”
BackgroundKuo, C., Hata, F., Yoshida, H., Yamatodani, A., & Wada, H. (1979) · Life Sciences · doi:10.1016/0024-3205(79)90341-2 · Cited by 77 · cited 1× · see citing works
“Further, AA was reported to decrease acetylcholinesterase activity in mice [101] and to positively restore presynaptic acetylcholine release [102].”
BackgroundAge-related decline of sodium-dependent ascorbic acid transport in isolated rat hepatocytes
Michels, A. J., Joisher, N., & Hagen, T. M. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(02)00678-1 · Cited by 75 · cited 1× · see citing works
“AA enters the cells through the sodium-dependent vitamin C transporters SVCT1 and SVCT2, a process favored by the electrochemical sodium gradient: due to its high capacity and low affinity, SVCT1 assures the intestinal and renal absorption and reabsorption [14].”
BackgroundJeong, S., & Cho, G. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.03.136 · Cited by 75 · cited 1× · see citing works
“Moreover, differentiation into adipocytes and osteocytes was significantly increased [38].”
BackgroundDhingra, D., Parle, M., & Kulkarni, S. K. (2006) · Journal of Medicinal Food · doi:10.1089/jmf.2006.9.281 · Cited by 75 · cited 1× · see citing works
“Further, AA was reported to decrease acetylcholinesterase activity in mice [101] and to positively restore presynaptic acetylcholine release [102].”
BackgroundLowered plasma vitamin C, but not vitamin E, concentrations in dementia patients.
Charlton, K. E., Rabinowitz, T. L., Geffen, L., & Dhansay, M. A. (2004) · PubMed · Cited by 74 · see citing works
Kim, S.-M., Lim, S.-M., Yoo, J.-A., Woo, M.-J., & Cho, K.-H. (2015) · Food & Function · doi:10.1039/c5fo00738k · Cited by 69 · cited 2× · see citing works
“Therefore, the supplementation with AA could exert protective effects against atherosclerosis and related systemic inflammation by reducing the oxidized LDL and macrophage phagocytosis, with reduced conversion to foam cells [42].”
BackgroundSil, S., Ghosh, T., Gupta, P., Ghosh, R., Kabir, S. N., & Roy, A. (2016) · Journal of Molecular Neuroscience · doi:10.1007/s12031-016-0817-5 · Cited by 68 · cited 1× · see citing works
“In particular, a colchicine-induced oxidative stress/neuroinflammation AD rat model [84] showed that administration of AA was effective in preventive memory impairment, and reducing inflammatory markers (TNF alpha, IL 1 beta), ROS, and nitrite levels in the hippocampus of AD rats.”
BackgroundVitamin C Transporter Gene Polymorphisms, Dietary Vitamin C and Serum Ascorbic Acid
Cahill, L. E., & El‐Sohemy, A. (2009) · Lifestyle Genomics · doi:10.1159/000314597 · Cited by 66 · cited 1× · see citing works
“Moreover, both AA transporter genotypes modify the strength of the correlation between dietary AA and serum levels [24].”
BackgroundAscorbic acid protects SH-SY5Y neuroblastoma cells from apoptosis and death induced by β-amyloid
Huang, J., & May, J. M. (2006) · Brain Research · doi:10.1016/j.brainres.2006.04.047 · Cited by 66 · cited 2× · see citing works
“Additionally, AA was shown to protect SH-SY5Y neuroblastoma cells from apoptosis mediated by Aβ [86], decreasing the rate of endogenous amyloid generation.”
BackgroundAscorbic acid, cognitive function, and Alzheimer's disease: A current review and future direction
Bowman, G. L. (2012) · BioFactors · doi:10.1002/biof.1002 · Cited by 66 · see citing works
Ellingsen, I., Seljeflot, I., Arnesen, H., & Tonstad, S. (2008) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2008.01.006 · Cited by 66 · cited 1× · see citing works
“Endothelial dysfunction is associated with arterial stiffness which, in turn, is a strong predictor for cognitive decline [124].”
BackgroundBallaz, S., Moráles, I., Rodrı́guez, M., & Obeso, J. A. (2013) · Journal of Neuroscience Research · doi:10.1002/jnr.23276 · Cited by 62 · cited 1× · see citing works
“Interestingly, it is also presumed that AA moderates the oxidative stress mediated by glutamate, protecting from excitotoxicity in the brain [56,88].”
BackgroundTwenty years of metallo-neurobiology: where to now?
Bush, A. I., & Curtain, C. C. (2007) · European Biophysics Journal · doi:10.1007/s00249-007-0228-1 · Cited by 61 · cited 1× · see citing works
“Metals can affect the morphology of Aβ, accelerating fibrillation and cytotoxicity of Aβ [71].”
BackgroundLin, J.-L., Huang, Y., Shen, Y.-C., Huang, H.-C., & Liu, P.-H. (2010) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.277 · Cited by 60 · see citing works
Intra-arterial vitamin C prevents endothelial dysfunction caused by ischemia-reperfusion
Pleiner, J., Schaller, G., Mittermayer, F., Marsik, C. L., MacAllister, R. J., Kapiotis, S., Ziegler, S., Ferlitsch, A., & Wolzt, M. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.06.011 · Cited by 58 · cited 1× · see citing works
“A model of ischemic-reperfusion [126] and BBB breakdown with reduced NO bioavailability may be considered a prototypical model to understand the pleiotropic roles of AA on endothelial function.”
BackgroundAntioxidants in Alzheimer's disease-vitamin C delivery to a demanding brain
Quinn, J. F., Suh, J. H., Moore, M. M., Kaye, J. A., & Frei, B. B. (2003) · Journal of Alzheimer s Disease · doi:10.3233/jad-2003-5406 · Cited by 57 · cited 1× · see citing works
“The study of Quinn [141] showed that the mean CSF-to-plasma AA ratio was significantly lower in AD compared with controls.”
ResultCapturing a Reactive State of Amyloid Aggregates
Parthasarathy, S., Yoo, B., McElheny, D., Tay, W. M., & Ishii, Y. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.511345 · Cited by 55 · cited 1× · see citing works
“Further evidence indicated a pro-oxidative role for AA in the interaction of the redox-active copper ions with misfolded amyloid β and AD pathogenesis, with particular relevance to catalytic sites for Cu+ present in full-length Aβ instead of in any particular Aβ conformation [82].”
BackgroundLadurner, A., Schmitt, C. A., Schachner, D., Atanasov, A. G., Werner, E. R., Dirsch, V. M., & Heiss, E. H. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.03.022 · Cited by 54 · cited 1× · see citing works
“Low levels of BH4 compromise eNOS function by promoting the transfer of electrons to oxygen molecules instead of L-arginine: in turn, eNOS produces a superoxide anion instead of generating NO [19].”
BackgroundAlzheimer’s disease and endothelial dysfunction
Bomboi, G., Castello, L., Cosentino, F., Giubilei, F., Orzi, F., & Volpe, M. (2009) · Neurological Sciences · doi:10.1007/s10072-009-0151-6 · Cited by 53 · cited 1× · see citing works
“Again, oxidative stress is considered a key relevant mediator, confirming the pathogenetic link between AD and vascular disease [116].”
BackgroundGarcía-Krauss, A., Ferrada, L., Astuya, A., Salazar, K., Cisternas, P., Martínez, F., Ramírez, E., & Nualart, F. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9497-3 · Cited by 52 · cited 1× · see citing works
“In turn, the direct contact of activated glial cells with neurons may generate immune mediators (nitric oxide, ROS, pro-inflammatory cytokines, and chemokines) that are neurotoxins, spreading inflammation in the central nervous system [78,79].”
BackgroundAntioxidants and endothelial nitric oxide synthesis
Heller, R., Werner‐Felmayer, G., & Werner, E. R. (2005) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-005-0009-7 · Cited by 48 · cited 1× · see citing works
“AA is also implicated in the endothelial integrity associated with NO bioavailability [17].”
BackgroundZandi, P. P. (2004) · Archives of Neurology · doi:10.1001/archneur.61.1.82 · Cited by 47 · see citing works
Berendsen, A. A. M., Santoro, A., Pini, E., Cevenini, E., Ostan, R., Pietruszka, B., Rolf, K., Cano, N., Caillé, A., Lyon-Belgy, N., et al. (2014) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2014.03.001 · Cited by 46 · see citing works
Ahmad, A., Shah, S. A., Badshah, H., Kim, M. J., Ali, T., Yoon, G. H., Kim, T. H., Abid, N. B., Rehman, S. U., Khan, S. H., et al. (2016) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527315666151110130139 · Cited by 46 · cited 2× · see citing works
“In addition, a rat model of ethanol-induced oxidative stress showed that AA was effective in counteracting ethanol-induced oxidative stress, neuroinflammation, and apoptotic neuronal loss with beneficial effects against ethanol damage to brain development [87].”
BackgroundAllahtavakoli, M., Amin, F., Esmaeeli-Nadimi, A., Shamsizadeh, A., Kazemi-arababadi, M., & Kennedy, D. D. (2015) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.12413 · Cited by 45 · cited 1× · see citing works
“In a model of stroke with substantial BBB disruption, AA significantly reduced BBB permeability [128].”
BackgroundPro-oxidant diet enhances β/γ secretase-mediated APP processing in APP/PS1 transgenic mice
Choudhry, F., Howlett, D. R., Richardson, J. C., Francis, P. T., & Williams, R. J. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.07.008 · Cited by 43 · see citing works
Chen, B., Wang, X., Chen, L.-W., & Luo, Z.-J. (2012) · Current Drug Targets · doi:10.2174/138945012799499749 · Cited by 40 · cited 2× · see citing works
“In the metabolic profile, inflammatory status was improved and, at a molecular level, the normalization of the phosphorylation of AKT kinase, transcriptional levels of NF-kappa B, protein kinase delta (PKC delta), peroxisome proliferator-activated receptor alpha (PPAR-alpha) and hypoxia-inducible factor-1 alpha (HIF1-…”
BackgroundUchio, R., Hirose, Y., Murosaki, S., Yamamoto, Y., & Ishigami, A. (2015) · British Journal of Nutrition · doi:10.1017/s0007114514003857 · Cited by 39 · cited 1× · see citing works
“Further, AA was found to modulate immune cell surveillance in SMP30 knockout mice [40].”
BackgroundSuppression of Amyloid β A11 Antibody Immunoreactivity by Vitamin C
Cheng, F., Cappai, R., Ciccotosto, G. D., Svensson, G., Multhaup, G., Fransson, L., & Mani, K. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.243345 · Cited by 39 · cited 2× · see citing works
“In the absence of AA, the temporary interaction between the Aβ domain and small NO-catalyzed release of anhydromannose (anMan)-containing oligosaccharides is prevented, with the increased induction of neurotoxic fibrillogenesis [103].”
BackgroundSanMartín, C. D., Adasme, T., Hidalgo, C., & Paula-Lima, A. C. (2012) · Neurodegenerative Diseases · doi:10.1159/000334901 · Cited by 38 · cited 1× · see citing works
“Brain accumulation of Aβ1-42 oligomers results in increased neuronal vulnerability to oxidative stress [64,65] neuroinflammation with impairment of synaptic plasticity [66], and neuronal death.”
BackgroundAumailley, L., Warren, A., Garand, C., Dubois, M. J., Paquet, É. R., Couteur, D. G. L., Marette, A., Cogger, V. C., & Lebel, M. (2016) · Aging · doi:10.18632/aging.100902 · Cited by 38 · cited 1× · see citing works
“In addition, in the same in vivo model, AA supplementation was shown to improve T cell-mediated acute response after liver injury, suggesting a modulation of the immune system [31].”
BackgroundHauss‐Wegrzyniak, B., & Wenk, G. L. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00087-3 · Cited by 37 · cited 1× · see citing works
“A previous study demonstrated that chronic administration of AA in the brain chronically infused with lipopolysaccharide and tiorphan was associated with increased deposition of Aβ amyloid plaques and increased Aβ neuronal immunoreactivity [92].”
BackgroundNutrigenomics at the Interface of Aging, Lifespan, and Cancer Prevention
Riscuta, G. (2016) · The Journal of Nutrition · doi:10.3945/jn.116.235119 · Cited by 37 · cited 1× · see citing works
“It is able to modulate telomeres activity, bioenergetics, DNA repair and oxidative stress, indicating a nutrigenomic role in the process of aging as well [49].”
BackgroundAscorbic acid prevents increased endothelial permeability caused by oxidized low density lipoprotein
May, J. M., & Qu, Z. (2010) · Free Radical Research · doi:10.3109/10715762.2010.508496 · Cited by 35 · cited 1× · see citing works
“An oxidized endothelium is known to increase BBB permeability [117] and the AA-associated protective mechanism on lipid metabolism was found to improve BBB endothelial disruption.”
BackgroundSustained choroid plexus function in human elderly and Alzheimer’s disease patients
Spector, R., & Johanson, C. E. (2013) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-10-28 · Cited by 35 · see citing works
Rahman, F., Frouh, F. A., Bordignon, B., Fraterno, M., Landrier, J., Peiretti, F., & Fontés, M. (2014) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2014.00029 · Cited by 34 · cited 1× · see citing works
“Since aging is associated with sarcopenia and defects in body weight, the current observations suggest that AA-mediated stem cell effects could play a role in the aging process [36,37].”
BackgroundVitamin C levels in blood are influenced by polymorphisms in glutathione S-transferases
Horská, A., Mišľanová, C., Bonassi, S., Ceppi, M., Volkovová, K., & Dušinská, M. (2010) · European Journal of Nutrition · doi:10.1007/s00394-010-0147-2 · Cited by 33 · see citing works
Huang, Y.-N., Lai, C.-C., Chiu, C.-T., Lin, J.-J., & Wang, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097276 · Cited by 32 · cited 1× · see citing works
“In line with these data, AA was also observed to suppress the lipopolysaccharide (LPS)-stimulated production of inflammatory mediators in neuron/glia co-cultures by inhibiting the MAPK and NF-κB signaling pathways [113].”
BackgroundNitric oxide mediates tightening of the endothelial barrier by ascorbic acid
May, J. M., & Qu, Z. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.12.046 · Cited by 31 · see citing works
Polidori, M. C., & Pientka, L. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-111034 · Cited by 31 · see citing works
Dallaire, A., Proulx, S., Simard, M. J., & Lebel, M. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-940 · Cited by 28 · cited 1× · see citing works
“Conversely, in the wild-type worms, AA only influenced the biological process of proteolysis [32].”
BackgroundLebel, M., Massip, L., Garand, C., & Thorin, É. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05189.x · Cited by 25 · cited 1× · see citing works
“It is noteworthy that in healthy mice, the beneficial effects of AA on health and lifespan were not significant and the supplementation significantly reduced the oxidative damage only in Wrn∆hel/∆hel mouse liver [30,34].”
BackgroundSong, J., Park, J., Kim, J. H., Choi, J. Y., Kim, J. Y., Lee, K. M., & Lee, J. E. (2015) · Experimental Neurobiology · doi:10.5607/en.2015.24.1.41 · Cited by 25 · cited 1× · see citing works
“Similarly, in a mouse model of cerebral ischemia, AA ameliorated BBB dysfunction by reversing tight junction claudin-5 and attenuated edema and neuronal loss [129].”
BackgroundLeelarungrayub, J., Yankai, A., Pinkaew, D., Puntumetakul, R., Laskin, J., & Bloomer, R. J. (2016) · Clinical Interventions in Aging · doi:10.2147/cia.s110718 · Cited by 25 · see citing works
Antioxidants and Dementia Risk: Consideration through a Cerebrovascular Perspective
Lam, V., Hackett, M. J., & Takechi, R. (2016) · Nutrients · doi:10.3390/nu8120828 · Cited by 25 · see citing works
Röhl, C., Armbrust, E., Herbst, E., Jess, A., Gülden, M., Maser, E., Rimbach, G. H., & Boesch, C. (2009) · Neurotoxicity Research · doi:10.1007/s12640-009-9108-z · Cited by 24 · cited 1× · see citing works
“It is well documented that AA is a first-line antioxidant defense to neutralize ROS reactivity, promoting the regeneration of endogenous antioxidants (GSH, catalase, vitamin E) [98].”
BackgroundLeelarungrayub, J., Laskin, J., Bloomer, R. J., & Pinkaew, D. (2015) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2015.12.001 · Cited by 24 · cited 1× · see citing works
“The associated AA antioxidant capacity also mediated anti-inflammatory effects by the reduction of pro-inflammatory cytokine secretion, especially TNF-alpha and interleukin-23 (IL-23) excluding interleukin-2 (IL-2) [51,52].”
BackgroundSarkar, S., Mukherjee, A. K., Swarnakar, S., & Das, N. (2016) · Current Alzheimer Research · doi:10.2174/1567205013666160625082839 · Cited by 23 · cited 1× · see citing works
“[87] recently reported that high-dose supplementation of AA reduced amyloidosis in AD mice (5XFAD) via the reduction of BBB disruption and mitochondrial alteration [96].”
BackgroundRahman, F., Bordignon, B., Culerrier, R. M., Peiretti, F., Spicuglia, S., Djabali, M., Landrier, J., & Fontés, M. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600506 · Cited by 21 · cited 1× · see citing works
“Since aging is associated with sarcopenia and defects in body weight, the current observations suggest that AA-mediated stem cell effects could play a role in the aging process [36,37].”
BackgroundPolidori, M. C., Ruggiero, C., Croce, M. F., Raichi, T., Mangialasche, F., Cecchetti, R., Pelini, L., Paolacci, L., Ercolani, S., & Mecocci, P. (2015) · Journal of Neural Transmission · doi:10.1007/s00702-014-1357-1 · Cited by 19 · cited 1× · see citing works
“Recently, a pathophysiological role of the vascular component in the pathogenesis of AD has been demonstrated [115].”
BackgroundCytoplasmic superoxide radical
Murakami, K., & Shimizu, T. (2012) · Communicative & Integrative Biology · doi:10.4161/cib.19548 · Cited by 19 · see citing works
Schwartz, B. (2014) · International Journal of Food Sciences and Nutrition · doi:10.3109/09637486.2014.898258 · Cited by 16 · see citing works
Aumailley, L., Dubois, M. J., Garand, C., Marette, A., & Lebel, M. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.10.012 · Cited by 16 · cited 1× · see citing works
“This study suggested that AA could be a potential cardiometabolic biomarker in patients with WS [39].”
BackgroundSurvival Rate in Patients Affected by Dementia Followed by Memory Clinics (UVA) in Italy
Ientile, L., Pasquale, R. D., Monacelli, F., Odetti, P. R., Traverso, N., Cammarata, S., Tabaton, M., & Dijk, B. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130002 · Cited by 16 · cited 1× · see citing works
“The increasing burden of this life-threatening condition [60] and the lack of disease-modifying drugs have guided the research towards preventive strategies, targeting AD modifiable risk factors [12].”
BackgroundSelf-citationPentosidine determination in CSF: a potential biomarker of Alzheimer’s disease?
Monacelli, F., Borghi, R., Pacini, D., Serrati, C., Traverso, N., & Odetti, P. R. (2013) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2012-0829 · Cited by 14 · cited 1× · see citing works
“In addition, lower concentrations of the fluorescent AGE pentosidine were observed in the CSF of AD patients, compared to healthy subjects, in support of a role for altered AGE metabolism in AD pathogenesis [73].”
BackgroundSelf-citationSato, Y., Amano, A., Kishimoto, Y., Takahashi, K., Handa, S., Maruyama, N., & Ishigami, A. (2013) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.12162 · Cited by 9 · cited 1× · see citing works
“In line with these data, Sato and colleagues suggested that AA plays an important role in preventing protein oxidation in the liver of SM30/gluconolactonase knockout mice, with potential implications in overall health and aging [41].”
ResultZheng, C., Sui, B., Hu, C., & Jin, Y. J. (2015) · PubMed · Cited by 7 · see citing works
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Diet and Inflammation in Cognitive Ageing and Alzheimer’s Disease
McGrattan, A., McGuinness, B., McKinley, M. C., Kee, F., Passmore, P., Woodside, J. V., & McEvoy, C. T. (2019) · Current Nutrition Reports · doi:10.1007/s13668-019-0271-4 · Cited by 395 · see citing works
Neuroinflammation in Alzheimer’s Disease
Onyango, I. G., Jauregui, G. V., Čarná, M., Bennett, J. P., & Stokin, G. B. (2021) · Biomedicines · doi:10.3390/biomedicines9050524 · Cited by 330 · see citing works
Plascencia‐Villa, G., & Perry, G. L. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8134 · Cited by 188 · see citing works
“Ascorbic acid supplementation showed neuroprotective properties, reducing free radicals and neuroinflammation, also iron chelation and Ab reduction (118).”
BackgroundDietary habits, lifestyle factors and neurodegenerative diseases
Popa‐Wagner, A., Dumbrava, D., Dumitrascu, D., Căpitănescu, B., Petcu, E. B., Surugiu, R., & Fang, W.-H. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.266045 · Cited by 187 · see citing works
Promoting Successful Cognitive Aging: A Ten-Year Update
Krivanek, T. J., Gale, S. A., McFeeley, B. M., Nicastri, C. M., & Daffner, K. R. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201462 · Cited by 181 · see citing works
“fatty acids [173, 174], antioxidant vitamins [175],”
Feng, J., Zheng, Y., Guo, M., Arés, I., Martínez, M., López-Torres, B., Martínez‐Larrañaga, M., Wang, X., Anadón, A., & Martínez, M. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.07.010 · Cited by 181 · see citing works
“However, it is also noteworthy that randomized clinical trials have still failed to demonstrate any association between vitamin C and pathophysiological remission of NDs 86 , suggesting that prevention of defi-ciency appears to be more beneficial than vitamin C supplementation.”
BackgroundPoor cognitive ageing: Vulnerabilities, mechanisms and the impact of nutritional interventions
Miquel, S., Champ, C., Day, J. E. L., Aarts, E., Bahr, B. A., Bakker, M. J., Bánáti, D., Calabrese, V., Cederholm, T., Cryan, J. F., et al. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.12.004 · Cited by 163 · see citing works
“…of accumulated cellular/tissue damage, and has been shown to underpin a wide variety of disorders associated with neurodegeneration (e.g. AD (Monacelli et al., 2017) and PD (Reeve et al., 2014), cardiovascular diseases (Ghebre et al., 2016), and metabolic dysfunction (Brewer et al., 2016)).”
Roles of Oxidative Stress in Synaptic Dysfunction and Neuronal Cell Death in Alzheimer’s Disease
Plascencia‐Villa, G., & Perry, G. L. (2023) · Antioxidants · doi:10.3390/antiox12081628 · Cited by 167 · see citing works
The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
“In the brain, AA has been increasingly found to promote several beneficial effects on neurodegeneration by direct neuroprotection against OS [116].”
BackgroundTherapeutic Perspective of Vitamin C and Its Derivatives
Meščić, A., Kraljević, T. G., & Raić‐Malić, S. (2019) · Antioxidants · doi:10.3390/antiox8080247 · Cited by 142 · see citing works
“Vitamin C has been shown to suppress free radical generation and attenuate oxidative damage resulting from the reactive oxygen species (ROS) [2,3].”
BackgroundInfluentialKonno, T., Melo, E. P., Chambers, J. E., & Avezov, E. (2021) · Cells · doi:10.3390/cells10020233 · Cited by 140 · see citing works
Inflammation in Neurological Disorders: The Thin Boundary Between Brain and Periphery
Cervellati, C., Trentini, A., Pecorelli, A., & Valacchi, G. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8076 · Cited by 137 · see citing works
“As exhaustively reviewed elsewhere, no clinical trials clearly demonstrate that a specific antioxidant intervention could be effective in AD (22, 128).”
Precision Redox: The Key for Antioxidant Pharmacology
Meng, J., Lv, Z., Zhang, Y., Wang, Y., Qiao, X., Sun, C., Chen, Y., Guo, M., Han, W., Ye, A., et al. (2021) · Antioxidants & Redox Signaling · doi:10.1089/ars.2020.8212 · Cited by 122 · see citing works
“damage and subsequently increase healthy longevity (9, 60, 71, 97), a number of experiments or clinical trials have shown harmful effects (57, 101).”
BackgroundPetrović, S., Arsić, A., Ristić-Medić, D., Cvetković, Z., & Vučić, V. (2020) · Antioxidants · doi:10.3390/antiox9111128 · Cited by 119 · see citing works
Xie, J., Gonzalez‐Carter, D., Tockary, T. A., Nakamura, N., Xue, Y., Nakakido, M., Akiba, H., Dirisala, A., Liu, X., Toh, K., et al. (2020) · ACS Nano · doi:10.1021/acsnano.9b09991 · Cited by 116 · see citing works
The mechanisms of ferroptosis and its role in alzheimer’s disease
Ma, H., Dong, Y., Chu, Y., Guo, Y., & Li, L. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.965064 · Cited by 115 · see citing works
Preventive and therapeutic potential of ascorbic acid in neurodegenerative diseases
Moretti, M., Fraga, D. B., & Rodrigues, A. L. S. (2017) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12767 · Cited by 114 · see citing works
Neurobiology of vitamin C: Expanding the focus from antioxidant to endogenous neuromodulator
Ballaz, S., & Rebec, G. V. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104321 · Cited by 106 · see citing works
Effect of aging on behaviour of mesenchymal stem cells
Fafián‐Labora, J., Morente-López, M., & Arufe, M. C. (2019) · World Journal of Stem Cells · doi:10.4252/wjsc.v11.i6.337 · Cited by 104 · see citing works
Nitti, M., Marengo, B., Furfaro, A. L., Pronzato, M. A., Marinari, U. M., Domenicotti, C., & Traverso, N. (2022) · Antioxidants · doi:10.3390/antiox11081613 · Cited by 96 · see citing works
“In AD, although promising results have been found with antioxidant supplementation in animal models, the results in humans yielded equivocal results, even if epidemiological data linking diet and risk of AD is rapidly increasing [301].”
ResultMediterranean diet and cognitive function: From methodology to mechanisms of action
Siervo, M., Shannon, O. M., Llewellyn, D. J., Stephan, B. C. M., & Fontana, L. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.09.018 · Cited by 86 · see citing works
Mei, J., Li, Y., Niu, L., Liang, R., Tang, M., Cai, Q., Xu, J., Zhang, D., Yin, X., Liu, X., et al. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00431-y · Cited by 85 · see citing works
“Vitamin C, a potent antioxidant, may treat cognitive impairment by suppressing the expression of pro-inflammatory genes, diminishing neuroinflammation, and preventing Aβ fibril formation [144], enhancing the therapeutic effect when used with SGLT2 inhibitors.”
BackgroundIn Pursuit of Healthy Aging: Effects of Nutrition on Brain Function
Melzer, T. M., Manosso, L. M., Yau, S., Gil‐Mohapel, J., & Brocardo, P. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22095026 · Cited by 90 · see citing works
Ding, Z., Chang, X., Fu, X., Kong, H., Yang, Y., Xu, H., Shan, Y., & Ding, S. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.07.236 · Cited by 79 · see citing works
The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review
Villagrán, M., Ferreira, J. L., Martorell, M., & Mardones, L. (2021) · Antioxidants · doi:10.3390/antiox10121894 · Cited by 73 · see citing works
“On the other hand, at the nervous system level, vitamin C acts as an antioxidant and suppresses the formation of beta-amyloid peptide and glutamatemediated excitotoxicity [22].”
BackgroundDynamics of ascorbic acid content in apple (Malus x domestica) during fruit development and storage
Lemmens, E., Alós, E., Rymenants, M., Storme, N. D., & Keulemans, W. (2020) · Plant Physiology and Biochemistry · doi:10.1016/j.plaphy.2020.03.006 · Cited by 70 · see citing works
The role of diet in preventing and reducing cognitive decline
Angeloni, C., Businaro, R., & Vauzour, D. (2020) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000605 · Cited by 70 · see citing works
“In order to combat oxidative stress and prevent ROS production, ascorbic acid and vitamin E have been extensively used.”
BackgroundInfluentialDietary natural products as epigenetic modifiers in aging-associated inflammation and disease
Evans, L. W., Stratton, M. S., & Ferguson, B. S. (2020) · Natural Product Reports · doi:10.1039/c9np00057g · Cited by 70 · see citing works
Vitamins in Alzheimer’s Disease—Review of the Latest Reports
Mielech, A., Puścion‐Jakubik, A., Markiewicz‐Żukowska, R., & Socha, K. (2020) · Nutrients · doi:10.3390/nu12113458 · Cited by 65 · see citing works
“It is a key antioxidant of the central nervous system [36].”
BackgroundIron and manganese-related CNS toxicity: mechanisms, diagnosis and treatment
Chen, P., Totten, M. S., Zhang, Z., Bucinca, H., Erikson, K. M., Santamarı́a, A., Bowman, A. B., & Aschner, M. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2019.1581608 · Cited by 66 · see citing works
“The antioxidant ascorbic acid (Vitamin C) was studied extensively, but was found ineffective in clinical trials [105].”
BackgroundA quantitative meta-analysis of vitamin C in the pathophysiology of Alzheimer’s disease
Hamid, M., Mansoor, S., Amber, S., & Zahid, S. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.970263 · Cited by 64 · see citing works
Dias, D., Portugal, C. C., Relvas, J. B., & Socodato, R. (2025) · Cells · doi:10.3390/cells14040243 · Cited by 66 · see citing works
Vitamin C and the Immune System
Jafari, D., Esmaeilzadeh, A., Mohammadi-Kordkhayli, M., & Rezaei, N. (2019) · Springer eBooks · doi:10.1007/978-3-030-16073-9_5 · Cited by 62 · see citing works
Ghosh, S., Durgvanshi, S., Agarwal, S., Raghunath, M., & Sinha, J. K. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200429011823 · Cited by 57 · see citing works
“Vitamin C, on the other hand, has been reported for its epigenetic regulation of AD-related genes and ROS scavenging property [119].”
Oxidative Stress in Tauopathies: From Cause to Therapy
Bartolomé, F. B., Carro, E., & Alquézar, C. (2022) · Antioxidants · doi:10.3390/antiox11081421 · Cited by 57 · see citing works
“Vitamin C has demonstrated a protective function against AD and other tauopathies [162,163].”
BackgroundPreventive and Therapeutic Potential of Vitamin C in Mental Disorders
Han, Q.-Q., Shen, T., Wang, F., Wu, P., & Chen, J.-G. (2018) · Current Medical Science · doi:10.1007/s11596-018-1840-2 · Cited by 54 · see citing works
Novel Antioxidant Properties of Doxycycline
Clemens, D. L., Duryee, M. J., Sarmiento, C., Chiou, A., McGowan, J. D., Hunter, C. D., Schlichte, S. L., Tian, J., Klassen, L. W., O’Dell, J. R., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19124078 · Cited by 54 · see citing works
Huang, W., Zhang, Z., Colucci, M., Deng, L., Yang, M., Huang, X., Zhou, X. J., Jin, Y., Lazzarini, E., Balbi, C., et al. (2024) · Environment International · doi:10.1016/j.envint.2024.108447 · Cited by 52 · see citing works
Sharma, K., Lee, H.-H., Gong, D.-S., Park, S., Yi, E., Schini‐Kerth, V. B., & Oak, M. (2019) · Environmental Pollution · doi:10.1016/j.envpol.2019.05.066 · Cited by 46 · see citing works
Distinctive Neurochemistry in Alzheimer’s Disease via 7 T In Vivo Magnetic Resonance Spectroscopy
Marjańska, M., McCarten, J. R., Hodges, J. S., Hemmy, L. S., & Terpstra, M. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180861 · Cited by 45 · see citing works
“Because extracellular concentration of Asc is substantially lower than intracellular concentration, the role that Asc plays in modulating neurotransmission [10, 39, 42] is unlikely to affect the Asc concentration measured in this study.”
BackgroundInfluentialXiong, L., Deng, N., Zheng, B., Li, T., & Liu, R. H. (2021) · Food & Function · doi:10.1039/d0fo03300f · Cited by 43 · see citing works
Mo, E., Ebedy, Y. A., Ibrahim, M. A., Farroh, K. Y., & Hassanen, E. I. (2022) · Scientific Reports · doi:10.1038/s41598-022-13960-1 · Cited by 43 · see citing works
Non-Enzymatic Antioxidants against Alzheimer’s Disease: Prevention, Diagnosis and Therapy
Varesi, A., Campagnoli, L. I. M., Carrara, A., Pola, I., Floris, E., Ricevuti, G., Chirumbolo, S., & Pascale, A. (2023) · Antioxidants · doi:10.3390/antiox12010180 · Cited by 45 · see citing works
Vitamin C Inhibits the Metabolic Changes Induced by Tet1 Insufficiency Under High Fat Diet Stress
Yuan, Y., Liu, C., Chen, X., Sun, Y., Xiong, M., Fan, Y., Petersen, R. B., Chen, H., Huang, K., & Zheng, L. (2021) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202100417 · Cited by 37 · see citing works
Kalmankar, N. V., Hari, H., Sowdhamini, R., & Venkatesan, R. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00033 · Cited by 37 · see citing works
Trends in Natural Nutrients for Oxidative Stress and Cell Senescence
Omidifar, N., moghadami, M., Mousavi, S. M., Hashemi, S. A., Gholami, A., Shokripour, M., & Sohrabi, Z. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/7501424 · Cited by 36 · see citing works
“It can also affect cell senescence via modulating nutrigenomic and epigenetic pathways that can be so important for the prevention of age-related diseases such as Alzheimer’s disease, insulin resistance, atherosclerosis, and neurodegeneration [39].”
BackgroundRistori, S., Bertoni, G., Bientinesi, E., & Monti, D. (2025) · Nutrients · doi:10.3390/nu17111837 · Cited by 41 · see citing works
“The primary neuroprotective mechanisms attributed to AAC include ROS-scavenging activity, neuroinflammation modulation, A β fibrillation inhibition, and the chelation of metals such as iron, copper, and zinc [214].”
Cellular toxicity driven by high-dose vitamin C on normal and cancer stem cells
Kim, T., Byun, J., Kwon, H. S., & Kim, D. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.02.083 · Cited by 36 · see citing works
Samuelsson, J., Najar, J., Wallengren, O., Kern, S., Wetterberg, H., Fässberg, M. M., Zetterberg, H., Blennow, K., Lissner, L., Rothenberg, E. M., et al. (2021) · European Journal of Nutrition · doi:10.1007/s00394-021-02688-9 · Cited by 38 · see citing works
Ramakrishna, K., Karuturi, P., Siakabinga, Q., Viswanadh, M. K., Dumala, N., Guntupalli, C., Nalluri, B. N., Venkateswarlu, K., Prasanna, V. S., Gutti, G., et al. (2024) · Phytotherapy Research · doi:10.1002/ptr.8122 · Cited by 34 · see citing works
“Vitamin C decreases β -amyloid generation and AChE activity and prevents endothelial dysfunction by regulating NO (Monacelli et al., 2017).”
BackgroundNeurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19
Owens, C. D., Pinto, C. B., Detwiler, S., Olay, L., Pinaffi‐Langley, A. C. D. C., Mukli, P., Péterfi, A., Szarvas, Z., James, J. A., Galván, V., et al. (2024) · Brain Communications · doi:10.1093/braincomms/fcae080 · Cited by 35 · see citing works
“209 In vitamin C deficiency, preclinical models showed elevated oxidative stress markers and increased A β levels, emphasizing its role in mitigating neurodegenerative processes.”
BackgroundAkhtar, A., Singh, S., Kaushik, R., Awasthi, R., & Behl, T. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102289 · Cited by 37 · see citing works
Šagud, M., Tudor, L., & Pivac, N. (2021) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2021.1906223 · Cited by 33 · see citing works
The Association between Dietary Nutrient Intake and Acceleration of Aging: Evidence from NHANES
Ma, J., Li, P., Jiang, Y., Yang, X., Luo, Y., Tao, L., Guo, X., & Gao, B. (2024) · Nutrients · doi:10.3390/nu16111635 · Cited by 32 · see citing works
“In addition, previous research has reported that caffeine, total dietary sugar, vitamin C, and vitamin K can each decelerate aging through distinct mechanisms [51–55].”
BackgroundNeuroprotective Natural Molecules, From Food to Brain
González-Fuentes, J., Selva, J. S., Moya‐López, C., Castro‐Vázquez, L., Lozano, M. V., Marcos, P., Plaza-Oliver, M., Robledo, V. R., Santander-Ortega, M. J., Villaseca-González, N., et al. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00721 · Cited by 34 · see citing works
Somade, O. T., Adeyi, O. E., Ajayi, B. O., Asunde, O. O., Iloh, P. D., Adesanya, A. A., Babalola, O. I., Folorunsho, O. T., Olakunle, D. A., & Lawal, O. F. (2022) · Metabolism Open · doi:10.1016/j.metop.2022.100179 · Cited by 32 · see citing works
“Antioxidant property of ASC confers its ability to suppress the production of beta-amyloid peptide and glutamate-mediated excitotoxicity [26].”
BackgroundMaherani, B., Harich, M., Salmieri, S., & Lacroix, M. (2018) · European Food Research and Technology · doi:10.1007/s00217-018-3211-4 · Cited by 32 · see citing works
Ding, H., Reiss, A. B., Pinkhasov, A., & Kasselman, L. J. (2022) · Medicina · doi:10.3390/medicina58081025 · Cited by 32 · see citing works
“The neuroprotective effects of vitamin C are also due to its mitigation of neuroinflammation and suppression of beta-amyloid proteins [112].”
BackgroundSultana, O. F., Hia, R. A., & Reddy, P. H. (2024) · Antioxidants · doi:10.3390/antiox13020202 · Cited by 31 · see citing works
The evolution of Alzheimer’s disease: From mitochondria to microglia
Yang, F., Liang, Y., Wang, X., Wang, J.-T., Gao, W., Ye, Q.-Y., Li, X., Yu, Y., & Li, H. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102838 · Cited by 32 · see citing works
Choi, Y. K., Kang, J.-I., Han, S. H., Kim, Y. R., Jo, J., Kang, Y. W., Choo, D. R., Hyun, J. W., Koh, Y. S., Yoo, E.-S., et al. (2020) · Nutrients · doi:10.3390/nu12051351 · Cited by 30 · see citing works
“L-AA has been effective in the treatment of oral diseases [7], cardiovascular diseases [8], iron deficiency anemia [9], diabetes [10], age-related eye disease [11], Alzheimer’s disease [12], and viral infections [13].”
BackgroundYang, L., & Zeng, C. (2018) · Molecules · doi:10.3390/molecules23123122 · Cited by 31 · see citing works
The Roles of Vitamins in Diabetic Retinopathy: A Narrative Review
Ruamviboonsuk, V., & Grzybowski, A. E. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11216490 · Cited by 29 · see citing works
“Vitamin C (ascorbic acid) is an antioxidant that provides beneficial effects on endothelial integrity which would result in improving endothelial dysfunction [30].”
BackgroundGan, L., Fan, H., Nie, W., & Guo, Y. (2018) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-018-0284-7 · Cited by 30 · see citing works
N-of-1 Clinical Trials in Nutritional Interventions Directed at Improving Cognitive Function
Soldevila‐Domenech, N., Boronat, A., Langohr, K., & de la Torre, R. (2019) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00110 · Cited by 27 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
“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 25 · see citing works
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 · see citing works
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 · see citing works
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 24 · see citing works
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 24 · see citing works
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 23 · see citing works
“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 · see citing works
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 · see citing works
“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 · see citing works
Denniss, R. J., & Barker, L. A. (2023) · Behavioral Sciences · doi:10.3390/bs13050388 · Cited by 22 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
“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 20 · see citing works
“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 20 · see citing works
“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 20 · see citing works
“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 · see citing works
“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 22 · see citing works
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 · see citing works
Marchi, F. D., Vignaroli, F., Mazzini, L., Comi, C., & Tondo, G. (2023) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527322666230608110201 · Cited by 19 · see citing works
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 · see citing works
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 19 · see citing works
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 23 · see citing works
Portugal, C. C. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.12.040 · Cited by 17 · see citing works
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 17 · see citing works
“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 · see citing works
Ganeshkumar, A., Suvaithenamudhan, S., & Rajaram, R. (2020) · Current Microbiology · doi:10.1007/s00284-020-02269-9 · Cited by 17 · see citing works
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 17 · see citing works
Tolédano, A., Rodríguez‐Casado, A., Álvarez, M., & Toledano‐Díaz, A. (2024) · Brain Sciences · doi:10.3390/brainsci14111101 · Cited by 19 · see citing works
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 · see citing works
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 16 · see citing works
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 · see citing works
“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
- 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
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Biochemistry › 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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