Fasting Mimicking Diet: Calorie Restriction increases Healthspan

Valter Longo, Professor of Gerontology and Professor of Biological Science at the University of Southern California, has for over 20 years explored the complex relationship between calorie restriction and good health. His recent research has further built upon our understanding of this relationship, and provided significant support for the use of a new method of calorie restriction in therapeutics.

Fasting Mimicking Diet based on Calorie Restriction found to be associated with increased healthspan.

Fasting Mimicking Diet based on Calorie Restriction found to be associated with increased healthspan.

Fasting Mimicking Diet based on Calorie Restriction found to be associated with increased healthspan.

Fasting Mimicking Diet based on Calorie Restriction found to be associated with increased healthspan.

In recent years Dr Valter Longo’s research into the relationship between human health and cyclical fasting has uncovered a startling range of positive health benefits associated with the practice; in June last year Longo showed that cyclical fasting can effectively trigger the regeneration of damaged immune systems and protect immune cells during chemotherapy, whilst in 2013 Longo published evidence that the progression of Alzheimer’s in mice can be slowed by a low-protein diet.

This year, Dr Longo has produced yet more evidence for the beneficial effects of calorie restriction – specifically a method of dietary restriction termed fasting mimicking dieting (FMD).

In a study published in July in Cell Metabolism, Longo showed that bi-monthly cycles of a restrictive diet designed to mimic fasting (FMD) resulted in “extended longevity, lowered visceral fat, reduced cancer incidence and skin lesions”, “cognitive improvements” and “immune system regeneration” in mice. Whilst in humans, 3 cycles of FMD was shown to “reduce multiple risk factors” associated with diabetes, cardiovascular disease, cancer and aging. (1)

Fasting Mimicking Diet induced Health Changes in Yeast, Mouse and Human.

(FIG). Summary of the health changes associated with FMD in yeast, mice and humans.
In yeast, periodic fasting improves stress-resistance and prolongs lifespan. In mice, FMD cycling increases lifespan and promotes immune and cognitive regeneration, whilst decreasing adiposity, cancer incidence and inflammatory disease incidence. In humans, FMD reduces numerous risk factors and biomarkers of aging.

Fasting Mimicking Diet induced Health Changes in Yeast, Mouse and Human.

(FIG). Summary of the health changes associated with FMD in yeast, mice and humans. In yeast, periodic fasting improves stress-resistance and prolongs lifespan. In mice, FMD cycling increases lifespan and promotes immune and cognitive regeneration, whilst decreasing adiposity, cancer incidence and inflammatory disease incidence. In humans, FMD reduces numerous risk factors and biomarkers of aging.

Fasting Mimicking Diet induced Health Changes in Yeast, Mouse and Human.

(FIG). Summary of the health changes associated with FMD in yeast, mice and humans. In yeast, periodic fasting improves stress-resistance and prolongs lifespan. In mice, FMD cycling increases lifespan and promotes immune and cognitive regeneration, whilst decreasing adiposity, cancer incidence and inflammatory disease incidence. In humans, FMD reduces numerous risk factors and biomarkers of aging.

Fasting Mimicking Diet induced Health Changes in Yeast, Mouse and Human.

(FIG). Summary of the health changes associated with FMD in yeast, mice and humans. In yeast, periodic fasting improves stress-resistance and prolongs lifespan. In mice, FMD cycling increases lifespan and promotes immune and cognitive regeneration, whilst decreasing adiposity, cancer incidence and inflammatory disease incidence. In humans, FMD reduces numerous risk factors and biomarkers of aging.

The Fasting Mimicking Diet was developed by Longo as a potentially safer, more moderate alternative to water-only fasting. The beneficial effects of prolonged, water-only fasting on human health are well documented, however it is still considered an extreme and risky dietary intervention, having the potential to cause negative effects as well as positive. FMD has therefore been designed by Longo as an effective alternative which “mimics the effects of fasting” whilst “minimizing the risk of adverse effects and the burden of complete food restriction.” (1)

The ultimate goal of Longo’s research is for FMD to be approved as a therapeutic tool; Dr Longo recently told the University of Southern California that he hopes FMD will “represent the first safe and effective intervention to promote positive changes associated with longevity and health span, which can be recommended by a physician.” (2)

One barrier to introducing fasting into the field of medicine is low patient compliance; statistics show that patients are often unable, or unwilling, to make significant, difficult life-style changes for the sake of their health. (3) Longo himself has acknowledged that “strict fasting is hard for people to stick to.” (2)

Fasting Mimicking Diet | Lifespan increases in mice undergoing fasting mimicking diet (FMD) vs control, non-dieting-mice (CTLR).

(FIGII). Graphical representation of the lifespan increase observed in mice undergoing fasting mimicking diet cycles (FMD) compared to control, non-dieting mice (CTRL).
The median lifespan of FMD mice was 28.3 months, compared to a median life span of 25.5 months in non-dieting mice, meaning FMD resulted in an 11% increase in median lifespan.

Fasting Mimicking Diet | Lifespan increases in mice undergoing fasting mimicking diet (FMD) vs control, non-dieting-mice (CTLR).

(FIGII). Graphical representation of the lifespan increase observed in mice undergoing fasting mimicking diet cycles (FMD) compared to control, non-dieting mice (CTRL). The median lifespan of FMD mice was 28.3 months, compared to a median life span of 25.5 months in non-dieting mice, meaning FMD resulted in an 11% increase in median lifespan.

Fasting Mimicking Diet | Lifespan increases in mice undergoing fasting mimicking diet (FMD) vs control, non-dieting-mice (CTLR).

(FIGII). Graphical representation of the lifespan increase observed in mice undergoing fasting mimicking diet cycles (FMD) compared to control, non-dieting mice (CTRL). The median lifespan of FMD mice was 28.3 months, compared to a median life span of 25.5 months in non-dieting mice, meaning FMD resulted in an 11% increase in median lifespan.

Fasting Mimicking Diet | Lifespan increases in mice undergoing fasting mimicking diet (FMD) vs control, non-dieting-mice (CTLR).

(FIGII). Graphical representation of the lifespan increase observed in mice undergoing fasting mimicking diet cycles (FMD) compared to control, non-dieting mice (CTRL). The median lifespan of FMD mice was 28.3 months, compared to a median life span of 25.5 months in non-dieting mice, meaning FMD resulted in an 11% increase in median lifespan.

FMD, therefore, was developed not just as a safer alternative to fasting, but also an easier, and far less burdensome, alternative; whilst water-only fasting requires no caloric intake on fasting days, FMD permits individuals to eat a limited amount during each of the monthly FMD cycles (~1090 kcal on day 1, 725 kcal on days 2-5). Under these conditions Longo reported “very high compliance” amongst subjects, bolstering hopes that if FMD becomes approved as a therapeutic treatment, patient adherence will be high. (1)

FMD can also be compared favourably to traditional dieting methods, as whilst traditional diets require long-term, persistent effort, FMD only requires restricted caloric intake for 5 days a month, and allows for normal eating habits all other days.

Fasting Mimicking Diet | Effects of prolonged-fasting in mice vs. non-dieting mice. (Image Credit: Christopher Hine, James R. Mitchell; Cell Stem Cell, Volume 14, Issue 6)

(FIGIII). Effects of prolonged-fasting in mice, compared to non-dieting mice.
In past mouse studies, true fasting over prolonged periods has been associated with stem cell-based immune-system regeneration and immune-protection during chemotherapy and aging.

Fasting Mimicking Diet | Effects of prolonged-fasting in mice vs. non-dieting mice. (Image Credit: Christopher Hine, James R. Mitchell; Cell Stem Cell, Volume 14, Issue 6)

(FIGIII). Effects of prolonged-fasting in mice, compared to non-dieting mice. In past mouse studies, true fasting over prolonged periods has been associated with stem cell-based immune-system regeneration and immune-protection during chemotherapy and aging.

Fasting Mimicking Diet | Effects of prolonged-fasting in mice vs. non-dieting mice. (Image Credit: Christopher Hine, James R. Mitchell; Cell Stem Cell, Volume 14, Issue 6)

(FIGIII). Effects of prolonged-fasting in mice, compared to non-dieting mice. In past mouse studies, true fasting over prolonged periods has been associated with stem cell-based immune-system regeneration and immune-protection during chemotherapy and aging.

Fasting Mimicking Diet | Effects of prolonged-fasting in mice vs. non-dieting mice. (Image Credit: Christopher Hine, James R. Mitchell; Cell Stem Cell, Volume 14, Issue 6)

(FIGIII). Effects of prolonged-fasting in mice, compared to non-dieting mice. In past mouse studies, true fasting over prolonged periods has been associated with stem cell-based immune-system regeneration and immune-protection during chemotherapy and aging.

“It’s not a typical diet because it isn’t something you need to stay on,” explained Longo.(2)

Whilst FMD appears to be safer and easier than other, more extreme methods of fasting, Longo warns that the practice should still “only be considered for use under medical supervision,” and acknowledges that although his findings show FMD to be both effective and “generally safe” they still require “confirmation by a larger randomized trial.” (1)

The importance of Longo’s recent research, and its potential impact on human health, has been reflected by the significant media attention which it has received, with Time, (4) The Washington Post, (5) New York Observer, (6) and Los Angeles Times (7) all recently publishing features on Dr Longo’s studies.

Valter D. Longo, Ph.D. is a biogerontologist / cell biologist known for his studies on the role of starvation and nutrient response genes on cellular protection aging and diseases, and for proposing that longevity is regulated by similar genes and mechanisms in many eukaryotes. In addition of heading the USC Longevity Institute, Longo is also the Edna M. Jones professor of biogerontology at the USC Davis School of Gerontology with a joint appointment at the USC Dornsife College of Letters, Arts and Sciences.

Valter D. Longo, Ph.D. is a biogerontologist / cell biologist known for his studies on the role of starvation and nutrient response genes on cellular protection aging and diseases, and for proposing that longevity is regulated by similar genes and mechanisms in many eukaryotes. In addition of heading the USC Longevity Institute, Longo is also the Edna M. Jones professor of biogerontology at the USC Davis School of Gerontology with a joint appointment at the USC Dornsife College of Letters, Arts and Sciences.

Valter D. Longo, Ph.D. is a biogerontologist / cell biologist known for his studies on the role of starvation and nutrient response genes on cellular protection aging and diseases, and for proposing that longevity is regulated by similar genes and mechanisms in many eukaryotes. In addition of heading the USC Longevity Institute, Longo is also the Edna M. Jones professor of biogerontology at the USC Davis School of Gerontology with a joint appointment at the USC Dornsife College of Letters, Arts and Sciences.

Valter D. Longo, Ph.D. is a biogerontologist / cell biologist known for his studies on the role of starvation and nutrient response genes on cellular protection aging and diseases, and for proposing that longevity is regulated by similar genes and mechanisms in many eukaryotes. In addition of heading the USC Longevity Institute, Longo is also the Edna M. Jones professor of biogerontology at the USC Davis School of Gerontology with a joint appointment at the USC Dornsife College of Letters, Arts and Sciences.

Image Credit

  • (FIGI). Summary of the health changes associated with FMD in mice and humans / (FIGII). Graphical representation of the lifespan increases observed in mice undergoing FMD cycles (FMD) compared to control, non-dieting mice (CTRL) from A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan (Sebastian Brandhorst, In Young Choi, Min Wei, Chia Wei Cheng, Sargis Sedrakyan, Gerardo Navarrete, Louis Dubeau, Li Peng Yap, Ryan Park, Manlio Vinciguerra, Stefano Di Biase, Hamed Mirzaei, Mario G. Mirisola, Patra Childress, Lingyun Ji, Susan Groshen, Fabio Penna, Patrizio Odetti, Laura Perin, Peter S. Conti, Yuji Ikeno, Brian K. Kennedy, Pinchas Cohen, Todd E. Morgan, Tanya B. Dorff, Valter D. Longo; Cell Metabolism, Volume 22, Issue 1, 7 july 2015, Pages 86-99).
  • (FIGIII). Effects of prolonged-fasting in mice, compared to non-dieting mice from Saying No to Drugs: Fasting Protects Hematopoietic Stem Cells from Chemotherapy and Aging (Christopher Hine, James R. Mitchell; Cell Stem Cell, Volume 14, Issue 6, 5 June 2014, Pages 704-705).

References

  1. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan [2015-06-18; Sebastian Brandhorst, In Young Choi, Min Wei, Chia Wei Cheng, Sargis Sedrakyan, Gerardo Navarrete, Louis Dubeau, Li Peng Yap, Ryan Park, Manlio Vinciguerra, Stefano Di Biase, Hamed Mirzaei, Mario G. Mirisola, Patra Childress, Lingyun Ji, Susan Groshen, Fabio Penna, Patrizio Odetti, Laura Perin, Peter S. Conti, Yuji Ikeno, Brian K. Kennedy, Pinchas Cohen, Todd E. Morgan, Tanya B. Dorff, Valter D. Longo, Cell Metabolism][Science Direct]
  2. Diet that mimics Fasting appears to slow Aging: Benefits demonstrated in Mice and Yeast; piloted in Humans [2015-06-18; PR Release, USC via EurekAlert]
  3. The challenge of Patient Adherence [2005 Sep; 1(3): 189–199; Leslie R Martin, Summer L Williams, Kelly B Haskard, and M Robin DiMatteo, Ther Clin Risk Manag. via PMC/NIH]
  4. Here’s a Secret to Living Longer You May Not Like [2015-06-18; Alexandra Sifferlin, Time]
  5. Here’s how a five-day diet that mimics fasting may ‘reboot’ the body and reduce cancer risk [2015-06-22; Ariana Eunjung Cha, The Washington Post]
  6. A Fast Examination of Intermittent Fasting [2015-07-01; David B. Samadi, Observer Style]
  7. A diet that mimics fasting is good for you, even if followed only for a few days [2015-06-23; Eryn Brown, Los Angeles Times]

Related Links

Christopher Edward Jones is a biochemist and writer currently affiliated with Queen Mary University of London, where he is part of a research group focusing on the restriction factors of HIV. In the past he has worked with multiple biomedical research groups in both industry and academia. He has a research interest in the biochemical mechanisms of virus restriction and a general interest in all areas of science.

Christopher Edward Jones is a biochemist and writer currently affiliated with Queen Mary University of London, where he is part of a research group focusing on the restriction factors of HIV. In the past he has worked with multiple biomedical research groups in both industry and academia. He has a research interest in the biochemical mechanisms of virus restriction and a general interest in all areas of science.

Christopher Edward Jones is a biochemist and writer currently affiliated with Queen Mary University of London, where he is part of a research group focusing on the restriction factors of HIV. In the past he has worked with multiple biomedical research groups in both industry and academia. He has a research interest in the biochemical mechanisms of virus restriction and a general interest in all areas of science.

Christopher Edward Jones is a biochemist and writer currently affiliated with Queen Mary University of London, where he is part of a research group focusing on the restriction factors of HIV. In the past he has worked with multiple biomedical research groups in both industry and academia. He has a research interest in the biochemical mechanisms of virus restriction and a general interest in all areas of science.



The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.

The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.

The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.

The Michelson Medical Research Foundation's Groundwork blog is brought to you thanks to the generous support of Dr. Gary K. Michelson and his wife, Alya Michelson.