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Autophagy Stimulation by Intermittent Fasting and Its Potential Neuroprotective Role in Alzheimer’s Disease
Corrales N, Vallejo-Bedia F, Olivares-Raya I, Avila J, García-Escudero V.. Preprints.org, 2026-08-24
Topic: Gut, metabolism and diet
Alzheimer’s disease (AD) is characterised by progressive accumulation of misfolded proteins and failure of cellular clearance pathways, particularly the autophagy–lysosomal system. Given the limited disease-modifying efficacy of current pharma-cological strategies, intermittent fasting (IF) has emerged as a potentially relevant non-pharmacological intervention capable of modulating energy metabolism, proteo-stasis and cellular stress responses. This review analyses the mechanisms through which IF and fasting-like metabolic states may stimulate macroautophagy and chap-erone-mediated autophagy, and evaluates their potential neuroprotective relevance in AD. Evidence from in vitro models and animal studies suggests that fast-ing-induced metabolic switching, particularly β-hydroxybutyrate production, can modulate AMPK–mTOR signalling, autophagic flux, oxidative stress, synaptic plas-ticity and Aβ/Tau-related proteostasis. However, the translation of these findings to humans remains incomplete. Current clinical studies suggest potential benefits on se-lected cognitive, sleep and metabolic outcomes, but rely mainly on indirect readouts such as neuropsychological testing, peripheral biomarkers, neuroimaging, metabo-lomics and microbiota-derived signatures. Larger, longer and biomarker-integrated randomised controlled trials using nutritionally supervised protocols are required to determine whether IF can safely produce clinically meaningful neuroprotection in AD without increasing frailty, sarcopenia or hypoglycaemic risk in older adults.
Key findings
- Evidence from in vitro models and animal studies suggests that fast-ing-induced metabolic switching, particularly β-hydroxybutyrate production, can modulate AMPK–mTOR signalling, autophagic flux, oxidative stress, synaptic plas-ticity and Aβ/Tau-related proteostasis.
- However, the translation of these findings to humans remains incomplete.
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Study details
- Evidence strengthHigh
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 27 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 17 of the 62 points we could judge it on, which is 27 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Preprints.org) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 17 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 17 of the 62 points we could judge it on is 27 out of 100. |
| Total | 27 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Corrales, N., Vallejo-Bedia, F., Olivares-Raya, I., Avila, J., & García-Escudero, V. (2026). Autophagy Stimulation by Intermittent Fasting and Its Potential Neuroprotective Role in Alzheimer’s Disease. Preprints.org. https://doi.org/10.20944/preprints202608.1636.v1
Vancouver
Corrales N, Vallejo-Bedia F, Olivares-Raya I, Avila J, García-Escudero V. Autophagy Stimulation by Intermittent Fasting and Its Potential Neuroprotective Role in Alzheimer’s Disease. Preprints.org. 2026. doi:10.20944/preprints202608.1636.v1.
BibTeX
@article{corrales2026-7ad35564,
author = {Corrales, N. and Vallejo-Bedia, F. and Olivares-Raya, I. and Avila, J. and García-Escudero, V.},
title = {{Autophagy Stimulation by Intermittent Fasting and Its Potential Neuroprotective Role in Alzheimer’s Disease}},
journal = {Preprints.org},
year = {2026},
doi = {10.20944/preprints202608.1636.v1},
url = {https://doi.org/10.20944/preprints202608.1636.v1}
}
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