Fasting-Mimicking Diet (FMD)

The Fasting-Mimicking Diet (FMD) is a nutritional protocol designed to achieve the benefits of fasting while still providing the body with nutrients. Developed by Dr. Valter Longo and his colleagues, FMD aims to mimic the physiological effects of traditional fasting, but in a way that is safer and more manageable for people to follow. The diet typically involves a reduced calorie intake, specific macronutrient ratios, and is followed for a period of five days each month.

Overview

FMD is based on the principle that certain dietary interventions can trigger some of the beneficial stress responses in the body that are activated by water fasting, such as autophagy (the process by which cells clean out damaged components), without the challenges and potential risks associated with complete food abstinence. The diet is low in calories, proteins, and sugars but high in unsaturated fats.

Research and Mechanisms

Research into FMD, led by Dr. Valter Longo and his team, has shown that it can lead to a reduction in biomarkers for aging, inflammation, and diseases in both animal models and humans. Studies have suggested that FMD can promote regenerative and rejuvenating changes in various biological systems, including the immune system, and may reduce risk factors associated with aging and age-related diseases.

Key Findings

Reduction in biomarkers for aging, inflammation, and diseases.
Improvement in markers of cardiovascular health.
Potential to promote autophagy and stem cell regeneration.

Potential Benefits

Weight Loss: FMD can lead to a reduction in body weight and body fat.
Longevity: Animal studies suggest that FMD may extend lifespan.
Health Improvement: Potential benefits include improved metabolic health, reduced inflammation, and enhanced cognitive function.

How to Follow FMD

The diet typically involves consuming specially formulated meal kits that are low in calories, proteins, and sugars but high in unsaturated fats for five consecutive days, followed by a return to a normal diet for the rest of the month. It is recommended to undergo this diet under medical supervision, especially for individuals with pre-existing health conditions.

Safety and Considerations

While FMD is generally considered safe for healthy individuals, it is not suitable for everyone. Specific groups, such as pregnant women, individuals with a low body mass index (BMI), or those with certain medical conditions, should avoid this diet. Consulting with a healthcare provider before starting FMD is crucial.

References

^{[10.1016/j.cell.2017.02.018]} - A study on the effects of FMD on markers of aging and disease.
^[1] - Research on the impact of FMD on lifespan and healthspan in mice.
^[2] - A study discussing the potential of FMD to promote human health and longevity.

Todo

2024, Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk ^[3]

References

↑ Horne BD et al.: Health effects of intermittent fasting: hormesis or harm? A systematic review. Am J Clin Nutr 2015. (PMID 26135345) [PubMed] [DOI] BACKGROUND: Intermittent fasting, alternate-day fasting, and other forms of periodic caloric desistance are gaining popularity in the lay press and among animal research scientists. Whether clinical evidence exists for or is strong enough to support the use of such dietary regimens as health interventions is unclear. OBJECTIVE: This review sought to identify rigorous, clinically relevant research studies that provide high-quality evidence that therapeutic fasting regimens are clinically beneficial to humans. DESIGN: A systematic review of the published literature through January 2015 was performed by using sensitive search strategies to identify randomized controlled clinical trials that evaluated the effects of fasting on either clinically relevant surrogate outcomes (e.g., weight, cholesterol) or actual clinical event endpoints [e.g., diabetes, coronary artery disease (CAD)] and any other studies that evaluated the effects of fasting on clinical event outcomes. RESULTS: Three randomized controlled clinical trials of fasting in humans were identified, and the results were published in 5 articles, all of which evaluated the effects of fasting on surrogate outcomes. Improvements in weight and other risk-related outcomes were found in the 3 trials. Two observational clinical outcomes studies in humans were found in which fasting was associated with a lower prevalence of CAD or diabetes diagnosis. No randomized controlled trials of fasting for clinical outcomes were identified. CONCLUSIONS: Clinical research studies of fasting with robust designs and high levels of clinical evidence are sparse in the literature. Whereas the few randomized controlled trials and observational clinical outcomes studies support the existence of a health benefit from fasting, substantial further research in humans is needed before the use of fasting as a health intervention can be recommended.
↑ Martineau AR et al.: Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017. (PMID 28202713) [PubMed] [DOI] [Full text] Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.Systematic review registration PROSPERO CRD42014013953.
↑ Brandhorst S et al.: Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nat Commun 2024. (PMID 38378685) [PubMed] [DOI] [Full text] In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary and exploratory analysis of blood samples from a randomized clinical trial (NCT02158897) and show that 3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as determined by magnetic resonance imaging) and increased lymphoid to myeloid ratio: an indicator of immune system age. Based on a validated measure of biological age predictive of morbidity and mortality, 3 FMD cycles were associated with a decrease of 2.5 years in median biological age, independent of weight loss. Nearly identical findings resulted from a second clinical study (NCT04150159). Together these results provide initial support for beneficial effects of the FMD on multiple cardiometabolic risk factors and biomarkers of biological age.

[pmid26135345-1] Horne BD et al.: Health effects of intermittent fasting: hormesis or harm? A systematic review. Am J Clin Nutr 2015. (PMID 26135345) [PubMed] [DOI] BACKGROUND: Intermittent fasting, alternate-day fasting, and other forms of periodic caloric desistance are gaining popularity in the lay press and among animal research scientists. Whether clinical evidence exists for or is strong enough to support the use of such dietary regimens as health interventions is unclear. OBJECTIVE: This review sought to identify rigorous, clinically relevant research studies that provide high-quality evidence that therapeutic fasting regimens are clinically beneficial to humans. DESIGN: A systematic review of the published literature through January 2015 was performed by using sensitive search strategies to identify randomized controlled clinical trials that evaluated the effects of fasting on either clinically relevant surrogate outcomes (e.g., weight, cholesterol) or actual clinical event endpoints [e.g., diabetes, coronary artery disease (CAD)] and any other studies that evaluated the effects of fasting on clinical event outcomes. RESULTS: Three randomized controlled clinical trials of fasting in humans were identified, and the results were published in 5 articles, all of which evaluated the effects of fasting on surrogate outcomes. Improvements in weight and other risk-related outcomes were found in the 3 trials. Two observational clinical outcomes studies in humans were found in which fasting was associated with a lower prevalence of CAD or diabetes diagnosis. No randomized controlled trials of fasting for clinical outcomes were identified. CONCLUSIONS: Clinical research studies of fasting with robust designs and high levels of clinical evidence are sparse in the literature. Whereas the few randomized controlled trials and observational clinical outcomes studies support the existence of a health benefit from fasting, substantial further research in humans is needed before the use of fasting as a health intervention can be recommended.

[pmid28202713-2] Martineau AR et al.: Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017. (PMID 28202713) [PubMed] [DOI] [Full text] Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.Systematic review registration PROSPERO CRD42014013953.

[pmid38378685-3] Brandhorst S et al.: Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nat Commun 2024. (PMID 38378685) [PubMed] [DOI] [Full text] In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary and exploratory analysis of blood samples from a randomized clinical trial (NCT02158897) and show that 3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as determined by magnetic resonance imaging) and increased lymphoid to myeloid ratio: an indicator of immune system age. Based on a validated measure of biological age predictive of morbidity and mortality, 3 FMD cycles were associated with a decrease of 2.5 years in median biological age, independent of weight loss. Nearly identical findings resulted from a second clinical study (NCT04150159). Together these results provide initial support for beneficial effects of the FMD on multiple cardiometabolic risk factors and biomarkers of biological age.

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