Fasting's potential in fighting cognitive decline needs more human trials

NewsGuard 100/100 Score

In a recent perspective review published in the journal Advances in Nutrition, researchers reviewed 14 relevant publications on human neurodegenerative disease (ND) research to unravel clinical protocols wherein fasting and caloric reductions (CRs) are used as anti-ND interventions. Unfortunately, despite preliminary results in murine models suggesting positive therapeutic promise for the field, human clinical trials were found to be exceedingly rare. This study highlights the need for additional human clinical trials before CR protocols are optimized to the point of presenting an effective weapon in clinicians’ arsenal in the fight against age-associated cognitive decline.

Perspective: The Impact of Fasting and Caloric Restriction on Neurodegenerative Diseases in Humans Image Credit: Marcin Malicki / ShutterstockPerspective: The Impact of Fasting and Caloric Restriction on Neurodegenerative Diseases in Humans. Image Credit: Marcin Malicki / Shutterstock

The link between diet and cognition and the potential for fasting as a therapeutic intervention

Neurodegenerative diseases (NDs) are the colloquial umbrella term for a spectrum of complex chronic neurological conditions characterized by a progressive decline in cognitive function, eventually resulting in the patient’s inability to perform even routine daily tasks. The condition is known to result from the age-associated denaturation of neurons comprising the brain and the central and peripheral nervous systems. Alarmingly, despite substantial advancements in clinical interventions against the condition, recent reports suggest that the global incidence of these diseases is on the rise, with more cases of multiple sclerosis (MS), Alzheimer’s disease (AD), and Parkinson’s disease (PD) recorded than ever before.

Decades of research suggest that NDs arise from a combination of genetic and environmental factors, with patients’ age presenting the strongest predictor of ND risk. Recently, studies have explored the potential of lifestyle interventions, particularly dietary modifications, in preventing or treating NDs, most of which remain without a cure. ‘Healthy diets’ which prioritize the consumption of fresh, unprocessed, predominantly plant-based foods, are increasingly being evaluated for their anti-cognitive-decline potential, with the Mediterranean diets (MDs) and ketogenic diets (KDs) consisting the most popular examples of these dietary patterns.

“Fasting (i.e., caloric restriction [CR] in various forms) has been used as an intervention to promote health since the beginning of civilization and has spread independently among different regions, cultures, and religions worldwide. It is believed to have already been established as a treatment method by Hippocrates in the 5th century BCE and has been used ever since by numerous medical schools to treat acute and chronic diseases.”

Unfortunately, while the positive impacts of fasting and CRs have been extensively proven and established in other chronic human diseases, including rheumatoid arthritis and some cancers, studies exploring the associations between these dietary practices and NDs remain rare, with a bulk of the literature highlighting the benefits of CRs in animal models, but limited human evidence remaining confounding.

About the study

In the present review, researchers aim to present a comprehensive, comparative ‘perspective’ on the associations between fasting or CRs and ND outcomes in humans while further attempting to elucidate the mechanisms by which the dietary practices may improve physical (and, by extension, cognitive) health. The review includes ND outcomes in individuals with and without clinically confirmed mild cognitive impairment (MCI). More than 70 papers were evaluated for study inclusion. However, only 14 met the review criteria (human clinical trials and primary intervention studies) and were included in the perspective’s synthesis.

Based on the outcomes reported by these 14 publications, the present review begins by defining fasting and calorific restrictions, presenting examples of beneficial dietary interventions, and highlighting the differences between the methodologies and applications of various fasting techniques, including intermitted fasting (IF), prolonged fasting (PF), and time-restricted eating (TRE). The research then explores and discusses evidence of CRs’ therapeutic potential in AD, PD, MS, and general MCI.

Finally, they discuss the potential mechanisms (e.g., gut microbiota perturbations) that may explain beneficial fasting-associated ND outcomes and compare and contrast fasting and ketogenic diets to help clinicians and the health-conscious make informed decisions about optimal health behavioral choices in this regard.

Study findings and conclusions

Of the 14 publications included in this review, four were conducted on patients with MS, only one on patients with AD, and alarmingly, none for PD patients (with the notable exception of the ongoing ExpoBiome study). The remaining studies, comprising the majority of human NR literature, explore the associations between fasting, CR, and MCI but are restricted to patients who are elderly, overweight, or obese.

While observed ND and MCI outcomes were found to be generally positive (beneficial to human health), results from fasting and CR studies investigating cognitive declines in aging adults (the most common MCI risk factor) produce heterogeneous and confounding results. This can be attributed to a common limitation of most ND human clinical trials – low sample size and suboptimal methodology.

Mechanistic investigations revealed that a majority of fasting and CR benefits may be attributed to gut microbial population modulations. As is the case with most non-ND chronic non-communicable diseases, gut microbial dysregulations were associated with hastened cognitive decline in patients with mild MCI. However, encouragingly, gut microbial eubiotics were found to slow or even reverse mild MCI symptoms, highlighting this field’s potential in future interventions against these debilitating conditions.

“Dietary recommendations for ND and the imminent application of the latter as a standard therapeutic intervention in daily clinical practice are of critical importance. Ongoing clinical trials, such as the ExpoBiome study, will provide insight into the mechanisms of fasting and the microbiota–gut–brain axis in relation to ND. Overall, this perspective emphasizes the need for additional clinical trials studying various fasting protocols, as this might potentially constitute a powerful new tool for preventing and treating ND.”

Journal reference:
Hugo Francisco de Souza

Written by

Hugo Francisco de Souza

Hugo Francisco de Souza is a scientific writer based in Bangalore, Karnataka, India. His academic passions lie in biogeography, evolutionary biology, and herpetology. He is currently pursuing his Ph.D. from the Centre for Ecological Sciences, Indian Institute of Science, where he studies the origins, dispersal, and speciation of wetland-associated snakes. Hugo has received, amongst others, the DST-INSPIRE fellowship for his doctoral research and the Gold Medal from Pondicherry University for academic excellence during his Masters. His research has been published in high-impact peer-reviewed journals, including PLOS Neglected Tropical Diseases and Systematic Biology. When not working or writing, Hugo can be found consuming copious amounts of anime and manga, composing and making music with his bass guitar, shredding trails on his MTB, playing video games (he prefers the term ‘gaming’), or tinkering with all things tech.


Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Francisco de Souza, Hugo. (2024, April 02). Fasting's potential in fighting cognitive decline needs more human trials. News-Medical. Retrieved on May 29, 2024 from

  • MLA

    Francisco de Souza, Hugo. "Fasting's potential in fighting cognitive decline needs more human trials". News-Medical. 29 May 2024. <>.

  • Chicago

    Francisco de Souza, Hugo. "Fasting's potential in fighting cognitive decline needs more human trials". News-Medical. (accessed May 29, 2024).

  • Harvard

    Francisco de Souza, Hugo. 2024. Fasting's potential in fighting cognitive decline needs more human trials. News-Medical, viewed 29 May 2024,


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Plant-based diets reduce cancer and heart disease risks, study shows