Intermittent Fasting (IF)/Fasting Mimicking Diet (FMD)

By Dr. Valter Longo, PhD

    Intermittent fasting IF is an eating pattern that involves switching between periods of fasting and eating. It does not specify which foods are favored or forbidden, but rather it dictates with timing and sometimes amounts.

     Fasting has been a practice throughout human evolution, resulting in the body having developed to function without food for extended periods of time1,2. Recently, scientific studies in various species have linked it to reductions in oxidative damage and inflammation, optimized energy metabolism, and enhanced cellular protection, indicating it may have the potential to help prevent and treat diseases1.

     It is important to note that the type of fasting promoted for improved health is very different from the consistently inadequate nutritional intake associated with starvation. Rather, it promotes right-sizing of consumption, ensuring sufficient nutrients1,2.

    There are several different ways of doing intermittent fasting, all of which involve splitting the day or week into eating and fasting periods. During the fasting periods, you eat either very little or nothing at all, but do drink water.

The following are common IF methods:

  • 5:2 (also known as FMD): Significantly restrict caloric intake, e.g., to 500-600 per day, on one to three nonconsecutive days of the week and eat normally the other four to six days.

  • 16/8: Skip breakfast or dinner and restrict the daily eating period to 8 hours, such as 1-9 p.m. or 8 a.m.-4 p.m., fasting for 16 hours in between. Some people prefer eating for 10 or 12 and fasting for 12 or 14 hours – this can be very individual.

  • Eat-Stop-Eat: Fast for 24 hours once or twice a week.

  • Alternate day fasting: Fast or significantly restrict caloric intake every other day.

  • The Warrior Diet: Eat small amounts of raw fruits and vegetables during the day, and one large meal in the evening. Some people find it easier or more advantageous to reverse the timing, having a large breakfast and then limiting intake for the rest of the day.

  • Spontaneous meal skipping: Skip meals occasionally, especially if you’re not hungry.

     IF and FMD are highly relevant to prevention and management of neurodegenerative diseases. They induce neuron repair, including autophagy (whereby old and damaged cell components are degraded and recycled)3, and reduce oxygen radical metabolism and cellular stress to protect neurons against harmful genetic and environmental factors and resist disease 4.

     In a two-group MS animal model study, the test group received a modified FMD for two weeks according to a 4:3 pattern: one-third regular caloric intake for three days, followed by free eating for four days. Compared with the control group, FMD animals had significant decreases in disease severity, immune cell infiltration into the spinal cord, and CNS demyelination. FMD also reversed disease-mediated CNS accumulation of autoimmune cells and enhanced the cell proliferation rate in the CNS, expression of brain-derived neurotrophic factor (BDNF), and remyelination markers 5.

     In another animal study, fasting every other day suppressed the secretion of pro-inflammatory cytokines and decreased disease severity by limiting spinal cord demyelination 6.

     In a randomized, controlled clinical study, MS patients were assigned either a 5:2 FMD, caloric restriction (CR) by 22%, or control diet. After eight weeks, both FMD and CR were associated with significant improvements in emotional well-being/depression scores relative to control 7.

References

1. Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. Feb 4 2014;19(2):181-92. doi:10.1016/j.cmet.2013.12.008

2. Visioli F, Mucignat-Caretta C, Anile F, Panaite SA. Traditional and Medical Applications of Fasting. Nutrients. Jan 19 2022;14(3)doi:10.3390/nu14030433

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

4. Martin B, Mattson MP, Maudsley S. Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing Res Rev. Aug 2006;5(3):332-53. doi:10.1016/j.arr.2006.04.002

5. Bai M, Wang Y, Han R, et al. Intermittent caloric restriction with a modified fasting-mimicking diet ameliorates autoimmunity and promotes recovery in a mouse model of multiple sclerosis. J Nutr Biochem. Jan 2021;87:108493. doi:10.1016/j.jnutbio.2020.108493

6. Razeghi Jahromi S, Ghaemi A, Alizadeh A, Sabetghadam F, Moradi Tabriz H, Togha M. Effects of Intermittent Fasting on Experimental Autoimune Encephalomyelitis in C57BL/6 Mice. Iran J Allergy Asthma Immunol. Jun 2016;15(3):212-9. 

7. Fitzgerald KC, Vizthum D, Henry-Barron B, et al. Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis. Mult Scler Relat Disord. Jul 2018;23:33-39. doi:10.1016/j.msard.2018.05.002

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