The fasting mimicking diet is, in essence, a clever strategy to pull in significant funding for the rigorous study of the use of forms of calorie restriction as a therapy. A fasting mimicking diet involves taking in just few enough calories to trigger most of the benefits of fasting. There must exist a dividing line in calorie intake at which nutrient sensor mechanisms determine that the body is in a state of fasting. Early research into fasting mimicking found that dividing line to be somewhere in the vicinity of 500 to 750 calories daily, but later studies use lower calorie levels. Another important point of calibration is to determine how long a fast must continue in order to produce the optimal, lasting benefits to metabolism. At this point, standard fasting mimicking is a five day exercise, with significant changes to the immune system occurring after the third day.
The real trick here, when it comes to enlisting the support of large entities in the world of regulation and medical development, is that while there is no good way to monetize the practice of fasting, there are very definitely ways to monetize a specific diet. An entire industry is focused on medical diets and the regulation thereof. Thus a specific fasting mimicking diet was created, patented, and fed into the regulatory approval process - and in the process pulled in funding and interest for this line of research and development. For those of us with little interest in these machinations, it is worth noting that the specifics of the diet are unimportant. Any sensible dietary composition that hits the calorie targets and duration should have the desired outcome.
In recent years, the primary focus for clinical trials of fasting mimicking has been its use in the treatment of cancer. It has long been known, as a matter of common wisdom in the medical community, that cancer patients tend do better as a result of forms of calorie restriction. Cancer is unfettered growth, and lowered calorie intake works against that growth in many different ways. Now much more robust data is emerging; today's research materials are an example of the results of that ongoing work.
A diet involving short-term, severe calorie restriction was safe, feasible, and resulted in a decrease of blood glucose and growth factor concentration, reduction in peripheral blood immunosuppressive cells, and enhanced intratumor T-cell infiltration in cancer patients receiving standard-of-care therapy, according to the results of a clinical trial. Researchers enrolled 101 patients in the study with various tumor types treated with different standard anticancer therapies.
The researchers administered a fasting mimicking diet (FMD) regimen to the study participants that consisted of a five-day, low-carbohydrate, low-protein, plant-derived diet, which provided up to 600 Kcal on day 1 and up to 300 Kcal on days 2, 3, 4, and 5, for a total amount of up to 1,800 Kcal in five days. The cycle was repeated every three or four weeks for up to a maximum of eight consecutive cycles. Calorie restriction was followed by a refeeding period of 16 to 23 days, during which patients were not subjected to specific dietary restrictions but were recommended to adhere to international guidelines for a healthy diet and lifestyle.
In 99 evaluable patients, the FMD regimen reduced the median plasma glucose concentration by 18.6 percent, serum insulin by 50.7 percent, and serum IGF-1 by 30.3 percent, with these modifications remaining stable over the course of eight consecutive cycles. In an analysis conducted on 38 patients at the end of a five-day FMD cycle, the researchers found a significant decrease of circulating immunosuppressive myeloid subpopulations and an increase of activated CD8+ T cells. Both of these effects occurred independently of concomitant antitumor therapies and were also observed in a small group of healthy volunteers.
To investigate the effects of the FMD diet on intratumor immunity, researchers performed an interim analysis of another ongoing trial testing a five-day FMD cycle seven to 10 days before surgery in early-stage breast cancer and melanoma patients. Specifically, they evaluated the tumor-infiltrating immune cells and transcriptomic immune profiles in 22 breast cancer patients for whom enough tumor tissue had been collected before and after the FMD. This analysis revealed a significant increase in tumor-infiltrating CD8+ T cells and other changes, indicating a functional switch toward an antitumor immune microenvironment following FMD.
In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMDs) enhance the activity of antineoplastic treatments by modulating systemic metabolism and boosting antitumor immunity. Here we conducted a clinical trial to investigate the safety and biological effects of cyclic, five-day FMD in combination with standard antitumor therapies. In 101 patients, the FMD was safe, feasible, and resulted in a consistent decrease of blood glucose and growth factor concentration, thus recapitulating metabolic changes that mediate fasting/FMD anticancer effects in preclinical experiments.
Integrated transcriptomic and deep-phenotyping analyses revealed that FMD profoundly reshapes anticancer immunity by inducing the contraction of peripheral blood immunosuppressive myeloid and regulatory T-cell compartments, paralleled by enhanced intratumor T-helper 1/cytotoxic responses and an enrichment of interferon-gamma and other immune signatures associated with better clinical outcomes in cancer patients. Our findings lay the foundations for phase II/III clinical trials aimed at investigating FMD antitumor efficacy in combination with standard antineoplastic treatments.