The issue of prolonged fasting has become a topic of increasing scientific interest because of the possible
impact of this practice on the body in terms of immune regulation, metabolic well-being, and cancer-related
biological functions. The long spells of caloric starvation, which are induced in prolonged fasting, result in
large-scale physiological changes, such as the alteration of energy metabolism, hormone levels, and
cellular responses to stress. The current paper discusses the consequences of long-term fasting regarding
immune response, the presence of biomarkers related to cancer, and safety implications on human
subjects. The review is based on the findings of observational research and clinical studies to assess the
evolution of innate and adaptive immune responses (i.e., leukocyte dynamics, inflammatory cytokine
profiles, and immune system regeneration after refeeding). Concurrently, the effects of long-term fasting
on cancer-biomarkers, including insulin, insulin-like growth factor-1 (IGF-1), glucose, C-reactive protein and
oxidative stress biomarkers are highly evaluated with special focus given on the processes of cell growth,
inflammation and tumor suppression. Although there are studies that report positive modulation of
biomarkers and decreased systemic inflammation, the results are still inconclusive because of the lack of
uniformity in fasting regimens, time, and subject profiles. Safety and tolerability is also considered and it
focuses on short-term adverse effects, including fatigue and electrolyte imbalance, and the risks of people
with vulnerable conditions such as cancer or metabolic disorders. Altogether, the data indicates that chronic
fasting can potentially provide biologically realistic advantages related to immune regulation and decrease
the risk of cancer; nevertheless, the existing evidence is not enough to justify the extensive application of
this practice. Clinical trials should be further conducted in large and well-designed human trials to determine
the best fasting regimens, safety during long period and clinical relevance.