The Fasting Mimicking Diet (FMD), a low-calorie diet that tricks your body into thinking it is fasting, while still consuming nutrient-dense foods shows promising effects on aging.

THE FASTING MIMICKING DIET AND HOW IT CAN HELP WITH AGING

Throughout evolution, humans existed in environments where food and resources weren’t always readily available. Presently, however, food is abundant in much of the western world, and reaching for a snack at any time of the day is commonplace. This overabundance often forces us into constant growth mode, causing us to overuse our digestive system, which is not only damaging for our bodies and metabolisms but also limits our bodies’ ability to focus on repair and renewal.

HOW DO WE COUNTERACT THIS?

Since the 1930’s research on animals has focused on restricting dietary access as a way to elongate lifespan and healthspan(13). Research has shown that both the amount of calories and the breakdown of macro and micronutrients in food play a role in aging and the development of chronic illness(2, 3, 7, 8, 12). The restriction of any part of the diet is called dietary restriction (DR). A substantial amount of animal research shows DR may and often does extend lifespan, which has led to a foundation for researching DR’s impact on human longevity with human participants.

WHAT IS THE FASTING MIMICKING DIET?

Recently, the Fasting Mimicking Diet (FMD), a low-calorie diet that tricks your body into thinking it is fasting, while still consuming nutrient-dense foods, has entered the DR picture. This diet was created and clinically tested by Dr. Valter Longo, a longevity expert with more than 20 years of experience dedicated to studying how to enhance human lifespan at the University of Southern California’s Longevity Institute. Due to the intense nature of fasting, Longo and his researchers crafted this diet for individuals hoping to reap the longevity benefits of fasting but who find fasting difficult and gruesome. 

The FMD is a low protein, low sugar, and reduced calorie 4-7 day plant-based diet with substantial micronutrient content. It’s macro and micronutrient composition have been scientifically formulated to provide the consumer with essential nutrients while encouraging their bodies to go into a state of light ketosis, in which they use stored energy reserves rather than glucose, derived from carbohydrates—essentially, providing the digestive system a break. It contains 34-54% of normal calorie intake and is 9-11% protein, 43-47% carbohydrates, and 44-46% fat (16). For reference, the diet recommended by the American Dietary Guidelines is: 10-25% protein, 45-65% carbohydrates and 20-35% fat. Using these metrics, you could craft your own DIY FMD, or if preferred, utilize an FMD from Dr. Longo’s company Prolon FMD. As per Prolon’s website, they recommend that the diet be used by healthy individuals, once every month for 3 months – or simply when seeking rejuvenation. 

HOW DOES THE FMD HELP WITH AGING BIOMARKERS?

Fasting has been shown to reduce inflammation, decrease insulin resistance, aid in controlling blood sugar, improve lipid parameters (triglycerides, cholesterol), and improve blood pressure, all parameters associated with slower aging(14, 15). It may also improve brain health as demonstrated by animal studies, increased stem cell function, and clearing out cellular damage (1, 10, 11, 14). Similarly, FMD helps to improve blood glucose levels, mobilize fatty acids, produce ketones, temporarily switch to ketone metabolism as opposed to glucose, and increase insulin sensitivity, as well as autophagy, or cellular clean-up, while minimizing adverse effects (4, 16). Considering these factors can be risk factors for disease of aging, this suggests FMD’s role as a tool to enhance human longevity.

HOW DOES THE FMD HELP WITH AGE RELATED DISEASES?

In mouse models, FMD has intervened in type 2 diabetes progression, restored insulin secretion and glucose balance, improved cognitive function and metabolism, decreased cancer incidences and bone loss, extended longevity, and rejuvenated the immune system(16, 4, 5, 17). Overall, these models have shown that FMD improves function and derails disease onset(16). Directly related to longevity, these models demonstrate FMD’s ability to significantly increase healthspan. While they also indicate a slight extending effect on lifespan as well, that extension has not proven to be significant (4). 

In humans, FMD has shown promise in ameliorating autoimmune conditions, multiple sclerosis (MS), and as an adjunct to chemotherapy treatment in cancer patients(4, 5, 6, 9, 16, 17). The benefits of FMD are said to be attributed to increased death of cells that no longer serve the body and the body’s increased ability to regenerate new healthy cells upon returning to normal eating patterns(6). One phase 2 randomized control trial investigating the impact of FMD on certain aging and age-related disease markers in healthy participants, showed that one cycle of 5-day FMD per month over a 3-month period, reduced the following risk factors for age-related disease: 

1. Body weight 
2. Waist circumference 
3. BMI 
4. IGF-1 
5. absolute total body fat 
6. Systolic blood pressure 

This shows a reduction of the risk factors for cancer, diabetes, and cardiovascular disease (CVD), and thus exemplifies FMD’s significant potential impact on longevity/aging. Furthermore, these effects likely last even 3 months after the intervention(16). 

An analysis on those with elevated risk for age-related illness was conducted finding more notable remaining beneficial effects on the following biomarkers: 

1. BMI 
2. Blood pressure 
3. Fasting glucose 
4. Triglycerides 
5. C-reactive protein(CRP) (inflammation) 
6. Low-density lipoprotein cholesterol (“bad cholesterol”) 
7. IGF1 

Overall, FMD is a medically designed diet that allows the body to reap the same benefits as fasting, whilst continuing the consumption of food. This diet has proven to be safe in the short-term, which has been echoed throughout both animal and human studies, emphasizing FMD’s assured ability to promote factors of longevity as well as levels of biomarkers that encourage optimized aging(16).

Author: Jacqueline Seymour

References: 

1. Alirezaei M, Kemball CC, Flynn CT, Wood MR, Whitton JL, Kiosses WB. Short-term fasting induces profound neuronal autophagy. Autophagy. 2010 Aug;6(6):702-10. doi: 10.4161/auto.6.6.12376. Epub 2010 Aug 14. PMID: 20534972; PMCID: PMC3106288.

2. Antosh, Michael, et al. “Comparative Transcriptional Pathway Bioinformatic Analysis of Dietary Restriction, Sir2, p53 and Resveratrol Life Span Extension in Drosophila.” Cell Cycle (Georgetown, Tex.), Landes Bioscience, 15 Mar. 2011, www.ncbi.nlm.nih.gov/pmc/articles/PMC3100872/. 

3. Blagosklonny MV;Campisi J;Sinclair. “Past, Present and Future.” Aging, U.S. National Library of Medicine, 2009, pubmed.ncbi.nlm.nih.gov/20157590/. 

4. Brandhorst, Sebastian, et al. “A Periodic Diet That Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan.” Cell Metabolism, vol. 22, no. 1, 2015, pp. 86–99., doi:10.1016/j.cmet.2015.05.012. 

5. Chia-Wei Cheng et al. Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes,Cell,Volume 168, Issue 5,2017,Pages 775-788.e12,ISSN 

0092-8674,https://doi.org/10.1016/j.cell.2017.01.040. 

6. Choi, I.Y., Lee, C., Longo, V.D., Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence, Molecular and Cellular Endocrinology (2017), doi: 10.1016/j.mce.2017.01.042. 

7. Fontana, L., et al. “Extending Healthy Life Span–From Yeast to Humans.” Science, vol. 328, no. 5976, 2010, pp. 321–326., doi:10.1126/science.1172539. 

8. Gems, David, and Linda Partridge. “Genetics of Longevity in Model Organisms: Debates and Paradigm Shifts.” Annual Review of Physiology, vol. 75, no. 1, 2013, pp. 621–644., doi:10.1146/annurev-physiol-030212-183712. 

9. Groot, Stefanie de, et al. “Fasting Mimicking Diet as an Adjunct to Neoadjuvant Chemotherapy for Breast Cancer in the Multicentre Randomized Phase 2 DIRECT Trial.” Nature News, Nature Publishing Group, 23 June 2020, www.nature.com/articles/s41467-020-16138-3. 

10. Lee et al. “Dietary Restriction Increases the Number of Newly Generated Neural Cells, and Induces BDNF Expression, in the Dentate Gyrus of Rats.” Journal of Molecular Neuroscience : MN, U.S. National Library of Medicine, 2000, pubmed.ncbi.nlm.nih.gov/11220789/. 

11. Li et al. “Chronic Intermittent Fasting Improves Cognitive Functions and Brain Structures in Mice.” PloS One, U.S. National Library of Medicine, 2013, pubmed.ncbi.nlm.nih.gov/23755298/. 

12. López-Otín, Carlos, et al. “The Hallmarks of Aging.” Cell, U.S. National Library of Medicine, 6 June 2013, www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/. 

13. McDonald, Roger B, and Jon J Ramsey. “Honoring Clive McCay and 75 Years of Calorie Restriction Research.” The Journal of Nutrition, American Society for Nutrition, July 2010, 

www.ncbi.nlm.nih.gov/pmc/articles/PMC2884327/. 

14. Mihaylova et al. Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging. Cell Stem Cell. 2018 May 3;22(5):769-778.e4. doi: 10.1016/j.stem.2018.04.001. PMID: 29727683; PMCID: PMC5940005. 

15. Rahmani J, Kord Varkaneh H, Clark C, Zand H, Bawadi H, Ryan PM, Fatahi S, Zhang Y. The influence of fasting and energy restricting diets on IGF-1 levels in humans: A systematic review and meta-analysis. Ageing Res Rev. 2019 Aug;53:100910. doi: 10.1016/j.arr.2019.100910. Epub 2019 May 19. PMID: 31116995.

16. Wei M et al.; “Fasting-Mimicking Diet and Markers/Risk Factors for Aging, Diabetes, Cancer, and Cardiovascular Disease.” Science Translational Medicine, U.S. National Library of Medicine, 2017, pubmed.ncbi.nlm.nih.gov/28202779/. 

17. Wei, S., Han, R., Zhao, J. et al. Intermittent administration of a fasting-mimicking diet intervenes in diabetes progression, restores β cells and reconstructs gut microbiota in mice. Nutr Metab (Lond) 15, 80 (2018). https://doi.org/10.1186/s12986-018-0318-3