Dr. Ewa Dąbrowska’s fasting — does the body really heal itself?

Aim of the study: We conducted a pilot randomized clinical trial to examine the effects of the fasting-mimicking diet (FMD) on autophagic flux and metabolic health markers in healthy humans. Thirty healthy participants were randomized to two oral formulations of FMD (ProLon and FMD2) or control for 8 days.

Results: These results suggest that FMD may improve autophagic flux and markers of metabolic health. FMD may serve as a non-pharmaceutical intervention to modulate autophagy; however, further investigation with larger sample sizes is needed to confirm and extend these findings. This clinical trial was sponsored by L-Nutra Inc. and registered on ClinicalTrials.gov (NCT06115551).

Aim of the study: Autophagy is a lysosomal degradation process and protective housekeeping mechanism to eliminate damaged organelles, long-lived misfolded proteins and invading pathogens. Autophagy functions to recycle building blocks and energy for cellular renovation and homeostasis, allowing cells to adapt to stress.

Results: Among several stress stimuli inducers of autophagy, fasting and CR are the most potent non-genetic autophagy stimulators, and lack the undesirable side effects associated with alternative interventions. Despite the importance of autophagy, the evidence connecting fasting or CR with autophagy promotion has not previously been reviewed. Therefore, our objective was to weigh the evidence relating the effect of CR or fasting on autophagy promotion. We conclude that both fasting and CR have a role in the upregulation of autophagy, the evidence overwhelmingly suggesting that autophagy is induced in a wide variety of tissues and organs in response to food deprivation.

Aim of the study: Time-restricted feeding (TRF) is a form of intermittent fasting that involves having a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic health in rodents and humans.

Results: Relative to the control schedule, eTRF decreased mean 24-hour glucose levels by 4 ± 1 mg/dl (p = 0.0003) and glycemic excursions by 12 ± 3 mg/dl (p = 0.001). In the morning before breakfast, eTRF increased ketones, cholesterol, and the expression of the stress response and aging gene SIRT1 and the autophagy gene LC3A (all p < 0.04), while in the evening, it tended to increase brain-derived neurotropic factor (BNDF; p = 0.10) and also increased the expression of MTOR (p = 0.007), a major nutrient-sensing protein that regulates cell growth. eTRF also altered the diurnal patterns in cortisol and the expression of several circadian clock genes (p < 0.05). eTRF improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans.

Aim of the study: Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders.

Results: Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, nematodes and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan- and healthspan-extending effects, as well as the cardioprotective and anti-arthritic consequences of fasting. Mechanistically, spermidine mediated these effects via autophagy induction and hypusination of the translation regulator eIF5A. In summary, the polyamine-hypusination axis emerges as a phylogenetically conserved metabolic control hub for fasting-mediated autophagy enhancement and longevity.

Aim of the study: Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle.

Results: Studies of IF (e.g., 60% energy restriction on 2days per week or every other day), PF (e.g., a 5day diet providing 750-1100kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects.

Aim of the study: Intermittent fasting, which includes periods of fasting and nutrition, has been considered a dietary approach for weight loss and metabolic health improvement. However, its potential benefits in autoimmune diseases have not been widely studied.

Results: Studies show that intermittent fasting may have beneficial effects on various autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus, by reducing inflammatory markers, modulating the immune system, altering and improving gut microbiota, and enhancing cellular repair mechanisms through autophagy. However, evidence regarding the effects of intermittent fasting on other autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, thyroid diseases, and psoriasis is limited and inconclusive. Nevertheless, further research is needed to determine optimal intermittent fasting guidelines and its long-term effects on autoimmune diseases. Overall, this literature review proves intermittent fasting may be a promising dietary intervention for managing autoimmune diseases.

Aim of the study: Intermittent fasting (IF) is an eating pattern in which individuals go extended periods with little or no energy intake after consuming regular food in intervening periods. IF has several health-promoting effects.

Results: Additionally, IF activates several biological pathways to induce autophagy, encourages cell renewal, prevents cancer cells from multiplying and spreading, and delays senescence. However, IF has specific adverse effects and limitations when it comes to people of a particular age and gender. Hence, a more systematic study on the health-promoting effects and safety of IF is needed. This article reviewed the research on the health-promoting effects of IF, providing a theoretical basis, direction for subsequent basic research, and information related to the clinical application of IF.

Aim of the study: Type 2 Diabetes Mellitus (T2DM) represents a major global health issue, with its incidence anticipated to increase markedly in the forthcoming decades. Efficient non-pharmacological therapies, especially dietary approaches, are essential for regulating glycemic control and facilitating weight reduction.

Results: IF shown substantial short-term advantages, encompassing marked decreases in HbA1c levels, fasting glucose, and body weight. Mechanistic discoveries emphasized better insulin sensitivity, augmented fat metabolism, and autophagy as key aspects. In contrast, CCR was linked to enduring metabolic enhancements, including decreased visceral fat and improved insulin sensitivity. Nevertheless, both dietary approaches demonstrated constraints.

Aim of the study: Intermittent fasting (IF) and Periodic fasting (PF) are biologically plausible non-pharmacological interventions. They trigger core metabolic reprogramming from glucose catabolism to ketogenesis and activate conserved nutrient-sensing networks including AMPK and sirtuins, coupled with mTOR/IGF-1 axis suppression.

Results: Clinically, time-restricted eating (TRE) and fasting-mimicking diets (FMDs) have demonstrated feasibility and short-term efficacy in pilot clinical studies, although their long-term translational potential and durability of benefits remain unproven. However, current research faces major bottlenecks: over-reliance on homogeneous animal models, insufficient high-quality long-term human trials, unresolved individual response heterogeneity, and the lack of validated non-invasive biomarkers and systematic long-term safety evidence. This mini-review systematically elaborates the core regulatory mechanisms of IF and PF through a hierarchical framework that distinguishes primary drivers from secondary consequences and speculative mechanisms, critically evaluates the evidence base across model systems, analyzes key translational barriers, and proposes a prioritized research agenda.

Aim of the study: Obesity-induced cognitive decline has been linked to alterations in brain autophagy. However, research concerning the high-fat diet (HFD) impacts on the brain still lacks evidence, and results are controversial.

Results: 24 male rats were allocated to control, fasting lean group, obese (HFD-fed), and obese fasting groups; behavioral tests, biochemical assays, and molecular analyses (inflammatory markers, BDNF, and autophagy-related genes) were conducted to assess cognitive function and underlying mechanisms. Our findings suggest that IF intervention significantly attenuated HFD-induced cognitive impairment and neuroinflammation, increased BDNF levels, improved histological alterations, decreased Beclin-1 and p62 immunohistochemical expression, and upregulated LC3 and ATG5 mRNA expression. IF can prevent HFD-induced cognitive disorders that could be mediated by the cerebral cortex and hippocampal autophagy dysfunction, emphasizing the importance of the autophagy pathway to normal neuronal functions.