Instalab ResearchBy the time someone has fasted for 36 hours, their body has shifted fully away from using stored glycogen as its primary energy source. Instead, fat reserves become the main fuel and ketones rise significantly.
One clinical report found that twice-weekly 36-hour fasts increased circulating ketones by fourfold compared to shorter fasts. Ketones are not just fuel; they also signal pathways linked to lower oxidative stress, cellular cleanup processes like autophagy, and improved metabolic resilience.
Inflammation markers respond as well. Controlled trials show reductions in C-peptide and MCP-1 after 36-hour fasting, with most of the changes occurring in the first 24 hours. Longer fasting maintains these lower levels, potentially reducing the chronic low-grade inflammation associated with aging and chronic disease. At the same time, fasting increases fat utilization and reduces insulin, shifting the body toward a more metabolically flexible state.
Evidence from human trials is still building, but several important themes are clear.
One is that 36-hour fasts consistently improve markers of metabolic health. Studies demonstrate reduced triglycerides, lower insulin resistance, and beneficial changes in pathways connected to aging. Another is that fasting lowers systemic inflammation, which is increasingly understood as a central driver of age-related decline.
Importantly, safety studies show that even people with type 1 diabetes can complete a supervised 36-hour fast without dangerous hypoglycemia or ketoacidosis, suggesting this duration is generally tolerable in a controlled setting. Healthy individuals, meanwhile, typically report hunger and fatigue but not serious side effects. The main drawback observed in exercise trials is reduced endurance performance when fasting overlaps with physical training.
Together, these findings suggest that a 36-hour fast has the capacity to activate many of the same protective mechanisms triggered by long-term calorie restriction, a dietary strategy proven to extend lifespan in multiple animal models.
Animal research suggests that more frequent fasting produces stronger longevity effects, but human studies indicate there is a practical limit. Over-fasting can cause nutrient deficiencies, lean mass loss, and diminished quality of life.
The strongest evidence comes from studies where participants fasted for 36 hours once or twice per week. In one 82-week case study, individuals practicing two nonconsecutive 36-hour fasts each week maintained weight loss, experienced lower hunger, and showed large increases in ketones without metabolic slowdown. Trials on alternate-day fasting, which mimic a 36-hour cycle, also show consistent improvements in insulin sensitivity, blood pressure, and cholesterol.
At the same time, longer-term randomized controlled trials suggest that slightly shorter fasts, such as once-weekly 24-hour fasts or multiple 20-hour fasts per week, deliver similar improvements with fewer complaints of fatigue. This raises the possibility that the main benefits of fasting come not from exceeding 24 hours every time, but from regularly extending the period in which the body is in a post-absorptive, fasting state.
Taken together, current evidence supports the idea that one 36-hour fast per week is enough to activate longevity-related pathways in most people, while a twice-weekly schedule may be appropriate for those who tolerate fasting well. Going beyond this does not appear to provide extra benefits and could create unnecessary risks.
Not everyone should approach fasting the same way. Age, baseline health, activity level, and medical conditions matter. Athletes may notice impaired endurance when fasting overlaps with training, so fasts should be scheduled around rest days. Older adults need to prioritize protein intake during eating periods to avoid losing muscle mass. People with diabetes or other chronic conditions should only attempt prolonged fasts with clinical supervision, as glucose and medication adjustments may be required.
For healthy adults, the safest and most evidence-based starting point is once per week. After several weeks, those who tolerate it well may increase to twice per week. More frequent attempts are not recommended until research provides stronger evidence.
A 36-hour fast is not a quick fix or a guarantee of a longer life, but it is one of the few practices supported by both mechanistic studies and clinical evidence to mimic the powerful effects of calorie restriction. By activating ketone production, lowering inflammation, and improving metabolic health, it places the body in a state that appears to promote healthier aging.
The key, however, is balance. Attempting a 36-hour fast once per week, and no more than twice, strikes the right middle ground between activating protective pathways and maintaining nutritional stability. More is not always better, and longevity comes from consistency over decades rather than short bursts of extreme restriction.
