Fasting Pills Mimic Real Fasting Benefits
Two clinical trials demonstrated that fasting-mimetic compounds provide metabolic benefits of fasting — improved cardiometabolic health — without requiring dietary changes. A second trial validated the formulation for cardiometabolic health, potentially opening doors for new longevity supplements.
The concept of "caloric restriction mimetics" (CRMs) has been a focus of aging research, with the goal of achieving the health benefits of fasting without the difficulty of caloric deprivation. These compounds aim to activate the same metabolic and stress-response pathways that are triggered when the body is in a fasting state. Early research into CRMs explored drugs that inhibit glucose metabolism or improve insulin sensitivity. The formulation for this particular "fasting pill" was developed after years of clinical research at UC Davis, led by Dr. Chris Rhodes, a nutritional biochemist. His team mapped the metabolic changes that occur in the human body during a 36-hour fast to identify key bioactive compounds that are naturally elevated. This research identified a synergistic blend of four molecules: spermidine, nicotinamide, palmitoylethanolamide (PEA), and oleoylethanolamide (OEA). Each ingredient in the formulation targets pathways associated with the benefits of fasting. Spermidine is known to induce autophagy, the body's cellular cleanup process, while nicotinamide supports energy metabolism and NAD+ levels. Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are involved in appetite signaling and activating PPAR-alpha, a key regulator of lipid metabolism and inflammation. The eight-week, double-blind, placebo-controlled trial involved 42 participants with elevated cardiometabolic risk factors. The group taking the fasting-mimetic supplement saw statistically significant reductions in total cholesterol, LDL cholesterol, oxidized LDL, and fasting glucose compared to the placebo group. Specifically, there was a 12.9% net drop in oxidized LDL and a 10.2% net change in LDL particle number versus placebo. Beyond the metabolic markers, the trial also demonstrated a notable impact on appetite and digestion. 91% of participants in the supplement group reported improved appetite regulation and reduced hunger, compared to 47% in the placebo group. The formulation was also found to be well-tolerated, with participants reporting less bloating and digestive discomfort. The research into palmitoylethanolamide (PEA), one of the key ingredients, dates back to the 1950s when it was identified as an anti-inflammatory agent. Its therapeutic potential was later highlighted in the 1990s by Nobel laureate Rita Levi-Montalcini for its role in regulating inflammation. This historical research provides a foundation for its inclusion in modern fasting-mimetic formulations. This approach differs from fasting-mimicking diets (FMDs), which typically involve a several-day, low-calorie, plant-based meal plan. FMDs, pioneered by researchers like Valter Longo, have also been shown to reduce risk factors for disease and lower biological age. The "fasting pill" aims to deliver the fasting signals at a molecular level, without any dietary changes. The decentralized nature of one of the clinical trials, conducted in partnership with People Science, allowed for real-world data collection directly from participants' homes. This included remote biosampling and daily adherence tracking through a mobile platform, showcasing a modern approach to clinical research in the field of metabolic science.
