Preclinical and human studies on chronic caloric restriction and water-only fasting show improvements in metabolic health and reduction of risk in cancer, diabetes, and cardiovascular diseases, but negative side-effects resulting from these approaches include loss of lean body mass, malnutrition, and impaired immune function. The fasting-mimicking diet (FMD) was developed to induce the body into a fasting state, with the goal of getting the benefits of water-only fasting while minimizing the negative health consequences. FMD is a plant-based, 5-day dietary intervention with low-calorie and low-protein content designed by Dr. Valter Longo and his team of scientists at the University of Southern California. Previous preclinical and human studies indicate FMD can induce cellular repair and autophagy, activate Yamanaka factors, improve body composition by reducing visceral fat, decrease systemic inflammation, and improve metabolic biomarkers such as IGF-1, HbA1C, and blood lipid levels.
Most recently, using data from a previous clinical trial, Dr. Longo and his team member Dr. Brandhorst revealed astounding results as 3 monthly cycles of FMD in human participants lowered biological age by 2.5 years, with reduced insulin resistance, lower liver fat, and better lymphoid to myeloid ratio, which is an indicator of immune system age. Biological age serves as a better measurement in predicting metabolic health, risk of diseases, and prediction of longevity than chronological age. In this study, the parameters used to calculate biological age were based on 10519 participants ages 30-90 from the Third National Health and Nutrition Examination Survey (NHANES). Biological age measurement is a more robust estimate of the rate of aging and risk of mortality because it is based on a set of multi-system clinical biomarkers.
In the previous trial, 100 participants were divided into 2 groups, with one group consuming regular diet and another group going through 1 cycle of FMD each month for 3 months. At the end of the trial, lower level of blood pressure, IGF-1, blood glucose, C-reactive protein, and blood lipid levels were observed in the experiment group, and body composition was improved with loss of abdominal fat and overall weight. In the most recent publication, data from 15 participants from the original trial that underwent 3 monthly FMD cycles were analyzed. At the end of this trial, those study participants experienced a reduction in subcutaneous, visceral, and liver fat, and most notably, 5 study participants had a 50% reduction in liver fat, setting FMD as a potential treatment for fatty liver diseases and hepatic steatosis. A 20% decrease in HOMA-IR score, a clinical measure for insulin resistance, was observed, meaning that participants had improved insulin sensitivity. Hemoglobin A1c levels decreased from 5.8 to 5.43, indicating the effect FMD has on normalizing blood glucose. A rejuvenating effect on the immune system was observed as the ratio of lymphoid to myeloid was improved.
The cohort of this study is predicated to be 3.5 years younger than the general American population at baseline, which could be due to enrollment bias of clinical trial volunteers which are often more motivated and health conscious. Even with this relatively healthy group of participants in the recent trial, a decrease of median biological age of 2.5 years was estimated after 3 cycles of FMD.
FMD is a multi-system approach which results in an initial reduction in cell number and organ size, associated with an increase in stem cell number and cellular reprogramming rate. Upon refeeding after each cycle, embryonic-like gene expression was exhibited with cell number and organ size returning to normalized condition, indicating systematic repair and rejuvenation of the body. Since risks for major chronic diseases are associated with increase in biological age, slowing or potentially reversing the aging process could lead to a prolonged healthspan. The role of FMD on decelerate aging is emerging with substantial clinical results. Stay tuned as more studies are being conducted in this exciting field.
– Lingyi Fan, Research Assistant at USC Longevity Institute