Updated and contextualized version of an article originally published on April 18, 2020
The article retains its original focus by presenting it through a scholarly and accessible perspective, supported by verifiable references.
Authors
- Dr. A. Colonnese – Nutrition biologist
- Roberto Panzironi –Independent researcher
Note editoriali
- First publication: April 18, 2020
- Last update: April 20, 2026
- Version: 2026 narrative revision
Initial note: This article is based on a previously published version and has been updated following scientific and public dissemination criteria. The text is for informational purposes only and does not replace medical advice; for health and treatment choices, always consult a healthcare professional.
IN BRIEF
- Therapeutic fasting and fasting-mimicking diets (FMD) show beneficial effects on metabolic biomarkers and some cellular regeneration processes in preclinical studies and pilot clinical trials.
- Proposed mechanisms include IGF-1 reduction, autophagy activation, and modulation of mTOR/PKA pathways; these mechanisms are plausible but do not guarantee identical effects in humans in every context.
- In clinical trials, IF/FMD can improve weight, blood pressure, insulin, and some inflammatory markers, but results vary by duration, frequency, protocol type, and studied population.
- Interesting results exist on hematopoietic system and pancreatic islet regeneration in animal models; clinical applications require larger and more controlled studies.
- Fasting is not without risks: it must be evaluated on a case-by-case basis, especially in fragile individuals, those with chronic diseases, or those undergoing pharmacological therapy.
Abstract: what does science say?
The term "therapeutic fasting" encompasses various practices: from absolute fasting (water only) to more moderate forms such as intermittent fasting (IF), alternate-day fasting, or fasting-mimicking diets (FMD). Studies on animal models and small human trials show that limited periods of reduced caloric intake can lower glucose and IGF-1 levels, promote the production of ketone bodies, activate cellular cleansing mechanisms (autophagy), and, in some experiments, stimulate stem cell regeneration. These biological effects are consistent with reductions in some cardiometabolic risk factors and with signs of improvement in inflammatory biomarkers. However, long-term clinical evidence on mortality, cancer risk, or human longevity is still insufficient: the observed effects depend on the duration of fasting, the composition of the supporting diet (if present), the frequency of cycles, and the clinical context. In summary, the literature supports biological plausibility and benefits on intermediate indicators, but it does not definitively state that therapeutic fasting increases lifespan or prevents all age-related diseases without risks or restrictions.
MAIN SECTION
Definition and variants of therapeutic fasting
"Therapeutic fasting" refers to different approaches: absolute fasting (water only), intermittent fasting (e.g., 16/8 hours of fasting daily), alternate-day fasting, 5:2 protocols (two days of reduced caloric intake), and fasting-mimicking diets (FMDs) which reduce calories and protein for a few days while maintaining minimal intake for safety. The practical differences are important because the composition and duration determine the metabolic response: for example, ketosis, reduction of IGF-1, and activation of autophagy tend to appear with prolonged fasting or well-structured FMDs, but are not identical in all forms of IF.
Main experimental evidence
In animal models, cycles of prolonged fasting or FMDs have shown effects on tissue regeneration, reduction of experimental tumors, and cognitive improvements. A key study described a fasting-mimicking diet (FMD) with benefits on multiple systems and on aging markers in mice; the same study also included preliminary data on a few human subjects treated with FMD cycles who showed reductions in weight, IGF-1, and other relevant biomarkers [1].
Regeneration of the hematopoietic and immune system: results and limitations
Studies conducted by the research group affiliated with USC have reported that periods of prolonged fasting in animal models reduce IGF-1/PKA and promote the regeneration of hematopoietic stem cells, with potential recovery of immune function following experimental chemotherapy [2]. Related results show that FMD protocols can promote pancreatic and beta-cell regeneration in murine models, with cellular observations also on human tissue in culture: these are promising data, but largely derive from preclinical studies or small clinical series and require large-scale confirmation [3].
Plausible biological mechanisms
The most studied mechanistic hypotheses involve reduction of anabolic stimuli (IGF-1, mTOR activity), increase in autophagy, modulation of PKA signaling, and increased production of ketone bodies. These changes can reduce oxidative stress and cellular inflammation and promote repair and renewal processes. Synthesis reviews agree on the plausibility of these mechanisms but highlight interspecies variability and the complexity of clinical transposition in different human contexts [4][5].
PRACTICAL SECTION
What it means in practice
For those seeking information: therapeutic fasting protocols are not all equivalent, and their effects vary based on duration, frequency, the composition of the diet on non-fasting days, and the individual's health status. In controlled trials, IF and some FMDs have shown improvements in body weight, waist circumference, insulin levels, and some inflammatory markers when compared to diets without intervention or with continuous caloric restriction; however, compared to traditional caloric restriction, the advantages for major clinical outcomes are not always evident, and adherence can be an issue [6][7].
When caution is needed
Fasting may be unsuitable or risky for people with diabetes taking hypoglycemic medications, during pregnancy, in pediatric age, in people with a history of eating disorders, in very elderly subjects, or with malnutrition. Furthermore, its application in oncology or chronic diseases requires controlled clinical protocols and medical supervision: experimental results indicating greater sensitivity of tumor cells to treatments under fasting conditions do not authorize DIY approaches or replace standard therapies [5].
KEY POINTS TO REMEMBER
- There is solid mechanistic evidence that fasting modulates metabolic pathways related to aging and cellular stress.
- In animal models, fasting and FMD have shown effects on regeneration and disease resistance; in humans, clinical evidence is still limited but promising for intermediate biomarkers.
- Not all protocols are the same: duration, composition, and frequency matter for the observed effects.
- Individuals with chronic conditions or taking medications must consult a doctor before starting fasting protocols.
- Larger and longer-term clinical studies are needed to confidently speak about mortality reduction or the prevention of specific diseases.
Limitations of Evidence
It is crucial to distinguish between observational studies, experimental animal studies, and randomized clinical trials in humans. Many positive results originate from murine models or small pilot studies: these offer insights into possible mechanisms but do not automatically establish definitive causal effects in humans. Available clinical trials often have limited sample sizes, relatively short durations, and methodological differences (types of fasting, inclusion criteria, measured outcomes), making it difficult to generalize the results. Furthermore, individual variability (age, sex, metabolic status, concomitant medications) influences the observed results. For these reasons, practical recommendations must be based on individualized assessments and consolidated evidence before extending protocols to at-risk populations.
Editorial Conclusion
The concept that scheduled periods of fasting or diets that mimic it can improve certain health biomarkers and activate regenerative processes is supported by a growing body of research. However, the translation of these findings into public health recommendations or generalized clinical prescriptions is not yet definitive. Methodological and clinical caution remains essential: therapeutic fasting can be a useful strategy in specific contexts and under supervision, but it is not a "universal cure." Randomized, longer-term studies with large populations are needed to evaluate benefits, risks, and long-term sustainability.
Editorial Note
This update has been prepared respecting criteria of scientific transparency and institutional divulgative language (EFV). The scientific references cited are verifiable via DOIs listed in the following section. The article does not constitute medical advice: for individual decisions, consult a doctor or a qualified healthcare professional.
SCIENTIFIC RESEARCH
- Brandhorst S, Choi IY, Wei M, et al. A periodic diet that mimics fasting promotes multi‑system regeneration, enhanced cognitive performance, and healthspan. Cell Metab. 2015;22(1):86–99. https://doi.org/10.1016/j.cmet.2015.05.012 [1]
- Cheng CW, Adams GB, Perin L, et al. Prolonged fasting reduces IGF‑1/PKA to promote hematopoietic‑stem‑cell‑based regeneration and reverse immunosuppression. Cell Stem Cell. 2014;14(6):810–823. https://doi.org/10.1016/j.stem.2014.04.014 [2]
- Cheng C‑W, Villani V, Buono R, et al. Fasting‑mimicking diet promotes Ngn3‑driven β‑cell regeneration to reverse diabetes. Cell. 2017;168(5):775–788.e12. https://doi.org/10.1016/j.cell.2017.01.040 [3]
- Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014;19(2):181–192. https://doi.org/10.1016/j.cmet.2013.12.008 [4]
- de Cabo R, Mattson MP. Effects of intermittent fasting on health, aging, and disease. N Engl J Med. 2019;381(26):2541–2551. https://doi.org/10.1056/NEJMra1905136 [5]
- Trepanowski JF, Kroeger CM, Barnosky A, et al. Effect of alternate‑day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: a randomized clinical trial. JAMA Intern Med. 2017;177(7):930–938. https://doi.org/10.1001/jamainternmed.2017.0936 [6]
- Gu L, Fu R, Hong J, Ni H, Yu K, Lou H. Effects of intermittent fasting in human compared to a non‑intervention diet and caloric restriction: a meta‑analysis of randomized controlled trials. Front Nutr. 2022;9:871682. https://doi.org/10.3389/fnut.2022.871682 [7]
- Varady KA, Bhutani S, Klempel MC, et al. Alternate‑day fasting for weight loss in normal weight and overweight subjects: a randomized controlled trial. Nutr J. 2013;12:146. https://doi.org/10.1186/1475-2891-12-146 [8]
Note: all DOIs listed above have been verified and link to the cited articles. If you would like a copy of the DOI check performed or further insights into the methodology of the listed studies, we can provide you with the full verification.