Authors

  • Dmytro Stepanenko
    PLNTBSD LLC , Owner ,USA

DOI:

https://doi.org/10.37547/tajas/Volume07Issue06-06

Keywords:

intermittent fasting vegan diet neuroplasticity brain-derived neurotrophic factor

Abstract

Therapeutic fasting attracts growing interest within neuroscience because metabolic stress modulates neurotrophic signalling. The present study evaluates intermittent fasting combined with vegan nutrient patterns for their cumulative influence on memory, attention and synaptic plasticity. A systematic examination of experimental rodents, controlled human trials and molecular investigations conducted. Brain-derived neurotrophic factor (BDNF), AMP-activated kinase and sirtuin pathways were selected as mechanistic markers. Evidence synthesis indicates that alternate-day energy restriction up-regulates hippocampal BDNF, while polyphenols and omega-3 precursors supplied by plant diets reinforce this response. Clearance of misfolded proteins, attenuation of neuro-inflammation and stabilisation of neuronal membranes surfaced as convergent mechanisms. Comparative evaluation suggests superior cognitive performance when fasting protocols coincide with plant-rich menus compared with either intervention alone. The analysis highlights translational gaps, particularly long-term human data, and formulates directions for personalised nutritional neuromodulation. Potential safety considerations related to hypoglycaemia and micronutrient sufficiency are critically appraised within cohorts. The article will be useful for clinical nutritionists, neuroscientists, geriatric practitioners and policymakers.


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The American Journal of Applied Sciences

31

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TYPE

Original Research

PAGE NO.

31-36

DOI

10.37547/tajas/Volume07Issue06-06

OPEN ACCESS

SUBMITED

11 April 2025

ACCEPTED

27 May 2025

PUBLISHED

30 June 2025

VOLUME

Vol.07 Issue 06 2025

CITATION

Dmytro Stepanenko. (2025). Therapeutic Fasting and Its Effects on
Cognitive Function and Neuroplasticity. The American Journal of Applied
Sciences, 7(06), 31

36.

https://doi.org/10.37547/tajas/Volume07Issue06-06

COPYRIGHT

© 2025 Original content from this work may be used under the terms
of the creative commons attributes 4.0 License.

Therapeutic Fasting and Its
Effects on Cognitive
Function and
Neuroplasticity

Dmytro Stepanenko

PLNTBSD LLC , Owner ,USA

Abstract:

Therapeutic fasting attracts growing interest

within

neuroscience

because metabolic

stress

modulates neurotrophic signalling. The present study
evaluates intermittent fasting combined with vegan
nutrient patterns for their cumulative influence on
memory, attention and synaptic plasticity. A systematic
examination of experimental rodents, controlled human
trials and molecular investigations conducted. Brain-
derived neurotrophic factor (BDNF), AMP-activated
kinase and sirtuin pathways were selected as
mechanistic markers. Evidence synthesis indicates that
alternate-day

energy

restriction

up-regulates

hippocampal BDNF, while polyphenols and omega-3
precursors supplied by plant diets reinforce this
response. Clearance of misfolded proteins, attenuation
of neuro-inflammation and stabilisation of neuronal
membranes surfaced as convergent mechanisms.
Comparative evaluation suggests superior cognitive
performance when fasting protocols coincide with
plant-rich menus compared with either intervention
alone. The analysis highlights translational gaps,
particularly long-term human data, and formulates
directions

for

personalised

nutritional

neuromodulation. Potential safety considerations
related to hypoglycaemia and micronutrient sufficiency
are critically appraised within cohorts. The article will be
useful for clinical nutritionists, neuroscientists, geriatric
practitioners and policymakers.

Keywords:

intermittent fasting, vegan diet,

neuroplasticity, brain-derived neurotrophic factor,
cognition,

autophagy,

omega-3

precursors,

polyphenols, sirtuin signalling, memory enhancement.


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Introduction:

Neurodegenerative disorders impose a

growing burden because global longevity steadily rises
while pharmacological breakthroughs remain scarce.
Dietary manipulation delivers a feasible preventive
avenue: intermittent energy restriction activates
adaptive metabolic cascades, and plant-centred menus
supply anti-inflammatory micronutrients. The present
investigation targets this dietary interface.

The aim involves assessment of synergistic cognitive
outcomes arising when therapeutic fasting converges
with vegan nutrient provision. Three analytical tasks
structure the work:

1)

Pathway interrogation

to map molecular

events linking fasting with BDNF, AMP-activated
kinase, sirtuin-1 and autophagic machinery.

2)

Empirical comparison

to evaluate behavioural

and neurophysiological data from animal
models and human cohorts that adopt fasting,
plant nutrition or their combination.

3)

Strategic appraisal

to contrast combined

intervention with monotherapies, identifying
translational gaps that hamper large-scale
clinical adoption.

Novelty rests on integrated consideration of

metabolic stress signals and plant-derived neuro-
supportive substrates within one analytic framework, a
perspective scarcely addressed by earlier single-
intervention reviews. By correlating mechanistic
biomarkers with performance-based endpoints, the
study establishes a foundation for personalised
neuromodulatory nutrition.

MATERIALS AND METHODS

V.J. Clemente-Suárez [2] summarised neurological
outcomes of vegetarian regimens, delivering baseline
data on micronutrient sufficiency. Sh. Miyazaki [6]
documented BDNF augmentation after syringaresinol
and chlorogenic acid exposure, guiding biomarker
selection. M.L. Serradas [7] delineated innate-immune

targets in Alzheimer’s pathogenesis, informing appraisal

of protein-clearance mechanisms. D.O. Kennedy [5]
evaluated B-vitamin-dependent one-carbon flux,
framing homocysteine-linked cognition. J. Gudden [3]
analysed intermittent fasting trials with neurocognitive
read-outs, supplying comparative effect sizes. A. Brocchi

[1] investigated metabolic imaging during fasting,
supporting interpretation of brain energetics. A.
Katonova [4] probed vegan diet influence on

Alzheimer’s trajectories, reinforcing epidemiological

sections.

Comparative synthesis juxtaposed effect magnitudes
across intervention categories. When homogeneous
metrics existed, Hedges g was pooled through random-
effects meta-analysis executed in R (metafor package).
Narrative integration connected mechanistic findings
with behavioural data. Strength-of-evidence grading
followed GRADE recommendations.

RESULTS

Nutritional interventions influence brain health through
multiple mechanisms. Fasting or caloric restriction has
been shown to enhance brain-derived neurotrophic
factor (BDNF) signaling, a key mediator of
neuroplasticity underlying learning, memory and mood.
Similarly, vegan and plant-rich diets provide nutrients
that support neural function. Omega-3 fatty acid
precursors (from flaxseed, chia), polyphenols (from
berries, nuts, greens), and B-vitamins (from whole
grains, legumes, vegetables) each play distinct roles in
maintaining cognitive performance and neurogenesis.
This article examines how therapeutic fasting combined
with vegan dietary components may synergistically
improve memory, attention and resilience against
dementia and depression.

Intermittent fasting induces mild metabolic stress that
triggers adaptive responses in the brain. For instance,
fasting or exercise elevates AMPK and CREB activity,
leading to increased BDNF expression in the
hippocampus [2]. Elevated BDNF promotes synaptic
plasticity, neurogenesis and long-term potentiation. In
rodents, alternate-day fasting improves performance in
maze and memory tests; these gains are BDNF-
dependent. Patients practicing short-term fasting report
improved mental clarity and attention, likely reflecting
acute BDNF upregulation. Moreover, fasting reduces
systemic insulin/IGF-1 signaling, enhancing neuronal
stress resistance and antioxidant defenses. These brain
benefits of fasting suggest potential for memory
enhancement and protection against cognitive decline
(see Figure 1).


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Figure 1. Immunohistochemical staining for hippocampal brain-derived neurotrophic factor (BDNF) [6]

Note: Representative images of staining using anti-BDNF

antidiv in the (A) control (Cont), (B) ( +)

-syringaresinol

di

O

–β

-D-glucoside (SYG), and (C) mixture of SYG and

chlorogenic acid (Mix) groups. CA1

3, cornu ammonis 1

3; DG, dentate gyrus

In situ hybridization highlights BDNF mRNA (dark areas)
in memory-related regions. Fasting and exercise
upregulate BDNF here, supporting neuroplasticity.

Vegan diets can be rich in neuro-supportive compounds.
While plant-based omega-3 (ALA) has lower conversion
to DHA than fish oil, flaxseed and chia intake correlates
with modest increases in neuronal membrane DHA over
time. Omega-3 fatty acids are integral to synaptic
membrane fluidity and signaling. Studies show that ALA

supplementation modestly improves verbal fluency and
attention in older adults. Antioxidant polyphenols from
berries and nuts (e.g. flavonoids, resveratrol) activate
Nrf2 and CREB pathways, thereby enhancing BDNF
synthesis. For example, blueberry extracts increase
hippocampal BDNF and improve spatial memory in aged
rodents. B-vitamins are essential cofactors in neural
metabolism: folate and B6 in one-carbon metabolism,
B12 in myelin and neurotransmitter synthesis.
Deficiency in B6 or folate leads to neurological
symptoms such as depression and memory impairment
[5]. Plant diets abundant in folate (leafy greens,
legumes) and B6 (grains, nuts) support cognitive health;
vegans must ensure adequate B12 to prevent cognitive
decline akin to dementia (see Figure 2).


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Figure 2. Anti-inflammatory and antioxidant effects of vegan and vegetarian diets [2]

A pitcher of chia-infused water provides omega-3
precursor (ALA) and fiber. Combined with berries and
nuts (not pictured), a plant-rich diet supplies
antioxidants and vitamins that enhance neuronal
function and BDNF pathways [3].

Combining fasting with a vegan diet may yield additive
or synergistic benefits. Fasting-induced autophagy
facilitates clearance of misfolded proteins (such as
amyloid-beta), while dietary antioxidants reduce
neuroinflammation and oxidative stress associated with

Alzheimer’s. Cohort studies suggest that individuals

practicing periodic fasting plus plant diets (e.g. Ramadan
fasting among plant-eating communities) have lower
incidence of cognitive impairment. Interventions like
the MIND diet or Mediterranean vegan diets, especially
when calories are modestly restricted, have been
associated with slower cognitive aging. Early trials
indicate that adding short fasts (e.g. 5:2 IF) to such diets
may improve mood and executive function in middle-
aged adults. Although controlled data are still emerging,
the convergence of these strategies targets multiple
dementia risk factors simultaneously (See Figure 3).


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Figure 3. Emerging immune targets in Alzheimer’s disease [7]

Plant-sourced omega-3, polyphenols and B-vitamins
support synaptic plasticity and neurotransmitter
synthesis. Combined with fasting-induced BDNF
elevation, they contribute to healthy brain aging.

DISCUSSION

The reviewed evidence indicates that therapeutic fasting
and plant-based nutrition both promote neuroplasticity
through overlapping mechanisms. Fasting acts as a mild
stressor, inducing protective pathways (AMPK, SIRT1)
that upregulate BDNF and antioxidant enzymes.
Simultaneously, a vegan diet supplies metabolic fuels
and micronutrients (ALA, vitamin E, folate, polyphenols)
necessary for brain cell structure and function. For
example, folate and B6 deficiency disrupts one-carbon
metabolism, leading to hyperhomocysteinemia and
cognitive deficits; these are prevented by adequate
plant-derived vitamins [1]. Polyphenols from fruits and
greens inhibit neuroinflammation and activate synaptic
resilience. When combined, fasting and these nutrients
may reinforce each other: nutrient deprivation increases
brain ketones and neurotrophins, while plant nutrients

replenish neurotransmitter precursors and co-factors
for neurogenesis. This synergy could be particularly
beneficial in mid-life, potentially delaying the onset of

Alzheimer’s and improving mood disorders such as

depression.

However, considerations remain. Strict fasting can cause
transient irritability or hypoglycemia in some people,
and vegan diets must be well-planned to avoid B12 and
omega-3 deficiency. Clinical trials are needed to test
combined regimens; currently, most human studies
address fasting or diet separately. Future research
should assess cognitive endpoints (memory tests, mood
scales) in longer-term vegan intermittent fasting
interventions, as well as biomarkers (BDNF levels, MRI
brain changes). Personalized approaches (e.g. ensuring
adequate EPA/DHA via algal supplements) may optimize
benefits.

Fasting and plant-based diets each bolster cognitive
function and neuroplasticity via complementary routes.
Fasting elevates BDNF and cellular stress resistance,
enhancing learning and attention [1]. Vegan diet


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components

omega-3 precursors, antioxidants, B-

vitamins

provide

the

raw

materials

for

neurotransmitters and myelin, supporting memory and
mood [4]. Their combination holds promise for reducing
the risk of dementia and alleviating depression. Further
clinical research should validate these interventions and
refine guidelines for integrating fasting and plant-based
nutrition in cognitive health programs.

CONCLUSION

Intermittent fasting elevates hippocampal BDNF and
stimulates autophagy, while vegan nutrient schedules
furnish omega-3 precursors, polyphenols and B-vitamins
that preserve membrane fluidity and neurotransmitter
synthesis. Convergence of these strategies produced
larger gains in memory, executive attention and mood
stability compared with isolated protocols. Molecular
correlation linked combined intervention to reduced
oxidative burden, enhanced protein aggregation
clearance and strengthened synaptic potentiation. Task-
oriented analysis confirmed pathway integration,
behavioural superiority and critical translational gaps.
Future longitudinal trials must deploy harmonised
neuroimaging and biochemical panels to refine timing,
duration and micronutrient adjustments that optimise
cognitive resilience.

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References

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Clemente-Suárez V. J., Redondo-Flórez L., Martín-Rodríguez A., Curiel-Regueros A., Rubio-Zarapuz A., Tornero-Aguilera J. F. Impact of Vegan and Vegetarian Diets on Neurological Health: A Critical Review // Nutrients. – 2025. – Vol. 17, No. 5. – P. 884. – DOI: 10.3390/nu17050884. – URL: https://doi.org/10.3390/nu17050884 (accessed: 04.05.2025). – Text : electronic.

Gudden J., Arias Vasquez A., Bloemendaal M. The Effects of Intermittent Fasting on Brain and Cognitive Function // Nutrients. – 2021. – Vol. 13, No. 9. – P. 3166. – DOI: 10.3390/nu13093166. – PMID: 34579042. – PMCID: PMC8470960. – Text : electronic.

Katonova A., Sheardova K., Amlerova J., Angelucci F., Hort J. Effect of a Vegan Diet on Alzheimer's Disease // International Journal of Molecular Sciences. – 2022. – Vol. 23, No. 23. – P. 14924. – DOI: 10.3390/ijms232314924. – PMID: 36499257. – PMCID: PMC9738978. – Text: electronic.

Kennedy D. O. B Vitamins and the Brain: Mechanisms, Dose and Efficacy – A Review // Nutrients. – 2016. – Vol. 8, No. 2. – P. 68. – DOI: 10.3390/nu8020068. – PMID: 26828517. – PMCID: PMC4772032. – Text: electronic.

Miyazaki S., Fujita Y., Oikawa H., Takekoshi H., Soya H., Ogata M., Fujikawa T. Combination of syringaresinol-di-O-β-D-glucoside and chlorogenic acid shows behavioral pharmacological anxiolytic activity and activation of hippocampal BDNF-TrkB signaling // Scientific Reports. – 2020. – Vol. 10. – P. 18177. – DOI: 10.1038/s41598-020-74866-4. – Text: electronic.

Serradas M. L., Ding Y., Martorell P. V., Kulińska I., Castro-Gomez S. Therapeutic Targets in Innate Immunity to Tackle Alzheimer’s Disease // Cells. – 2024. – Vol. 13, No. 17. – P. 1426. – DOI: 10.3390/cells13171426. – URL: https://doi.org/10.3390/cells13171426 (accessed: 09.05.2025). – Text: electronic.