10 Reasons Why FASTING could be your Elixir Of Life

The elixir of life is a potion that humans have sought to attain eternal life or youth and cure all diseases

The concept has originated in many cultures independently with the Alchemists seeking various means of formulating the elixir. This idea arose independently in ancient India, China and Mesopotamia before it became popular in Europe. The first known description was in the Epic of Gilgamesh from ancient Mesopotamia. Gilgamesh seeks the elixir of life after being distraught at the loss of his beloved companion Enkidu.

Many emperors in ancient China sought the elusive elixir, including the Qin dynasty who sent a Taoist alchemist and 1000 young men and women to the eastern seas in its search. According to the legend, they never saw the elixir. Still, they found Japan, which happens to have one of the world’s most extended average lifespans.

The consumption of Amrita, the elixir of life, described in ancient Hindu scriptures, granted immortality. In the European alchemical tradition, the ‘philosopher’s stone, which could turn base metals into precious ones, had the power to grant eternal life. Though our quest seeking elixirs of life has not met with success, the most promising elixir to date has come from an unexpected source, consuming less food.

In 1935, Clive McCay showed that restriction of calories without malnutrition prolongs mean and maximal lifespan in rats compared with those allowed to eat freely. Subsequent experiments in mice showed that ~40% reduction in calorie consumption resulted in a ~50% extension in lifespan. [1]

The potential of caloric restriction to extend lifespan has captured the imagination of many prominent scientists. It has created a large sub-field of aging research. Since then, caloric restriction has been found to extend lifespan in nearly 30 species. It remains the most robust way to extend lifespan in the laboratory. Numerous fasting methods involve restricting specific nutrients (carbohydrates or proteins generally) or for defined periods (intermittent fasting).  

Since McCay’s pioneering experiments 85 years ago, a large body of data has emerged, which further argues for the benefits of caloric restriction in extending lifespan and healthspan.

Aging is the decline in the function of various bodily processes accompanied by the emergence of various age-associated diseases. Healthspan is defined by the period of life that is relatively disease-free. For many, this has become a goal to aspire for. We discuss below ten most compelling reasons backed by peer-reviewed scientific publications that argue why some form of fasting should be part of everyone’s lifestyle.

1. Fasting can extend the lifespan

Fasting has emerged as the most robust way to extend lifespan in laboratory settings. Rigorous studies performed on a range of animals from fruit flies to rodents to primates have successfully shown an increase in the average and maximum lifespan in the animals that underwent fasting. [2] Though it will be sometime before we know whether fasting extends lifespan in humans, fasting reduces age-related diseases, increasing humans’ healthspan. [3] Furthermore, data from 19 studies that measured outcomes under standard settings from ~1.5 million adults found that overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. [4] All-cause mortality is generally lowest with a Body Mass Index (BMI) of 20.0 to 24.9. BMI is a person’s weight in kilograms divided by the square of height in meters. BMI is an inexpensive and easy method to determine whether you are underweight, healthy, overweight or obese. Calculate your BMI here.

2. Fasting, the ancestral way

An important question to ask is, why does fasting improve health?

Evolutionary biologists suggest—to deal with situations

when nutrients lack, organisms have evolved ‘time out’ strategies

that allow prolonged survival until nutrients become plenty.

Such strategies are even seen in bacteria that form spores to avoid starvation periods and continue to exist in a dormant state with a lower metabolism, till nutrients become plenty.

It is thought that similar mechanisms are at play in mammals that help them deal with extended periods of starvation. Our ancestors evolved in an environment where food scarcity was the norm. It is worth noting that a well-nourished (person) can survive without food for 1-2 months.

Periods of food scarcity were frequent in our past before we adopted an agrarian lifestyle about 10,000 years ago and industrialization of our society in the 1800s. Thus our body evolved strategies to sustain and function optimally despite starvation. For example, we developed mechanisms to overeat when food was plenty and store it as fat. We are well adapted to switch between and exploit different food reserves in the body like glucose and fats to generate energy. [5] Thus our body evolved to respond to fasting periods. Over the last 8 decades, the research shows that fasting without malnutrition is not accompanied by significant side effects but several associated benefits.

3. Fasting fights off age-related diseases, including Type II diabetes

An essential question in the field has been whether the postponing of death by various food restriction methods also delay age-related diseases. Overall the data from multiple model organisms show postponement of age-related disease. Perhaps the most extensive data comes from alleviating age-related diabetes, also known as Type II diabetes. Type II diabetes is caused by a combination of lack of secretion of insulin and insulin resistance, leading to increased blood sugar.

Nearly 10% of the US population is diabetic, and almost one-third pre-diabetic.

Insulin is a hormone synthesized in the pancreas and one of the body’s leading sugar management tools. The degree to which a unit of insulin lowers the blood sugar is called insulin sensitivity.  When our body, especially muscle cells, become less responsive to insulin, the insulin sensitivity goes down, which is known as insulin resistance. 

Consuming high levels of carbohydrates leads to gradual insulin resistance with age. Furthermore, insulin resistance leads to a severe condition called metabolic syndrome. That puts you at risk of high blood sugar, increased waist circumference, and high blood pressure.

Metabolic syndrome makes one vulnerable to health conditions, including cardiovascular disease and accelerated death. Studies show an improvement in insulin resistance in humans with fasting. A meta-analysis of many trials assessing the effects of fasting on humans confirmed that it improves insulin sensitivity and glucose metabolism. The result is attributed to several factors, including reducing the pro-obesity hormone leptin and increasing the pro-insulin sensitivity hormone adiponectin. [6]

4. Fasting protects against several types of cancer

Restriction of calories reduces the overall risk of cancer in both mice and monkeys. The risk of several cancers in humans is enhanced by obesity. As cancer cells require nutrients to grow, fasting is an effective way to starve cancer. Furthermore, fasting alters the growth factor and the metabolite levels making the environment difficult for cancer cells to thrive. [7] Fasting even improves the efficacy of chemo- and radio-therapies. [8]

5. Fasting helps burn fat and improve mitochondrial health

Though fat gets demonized often, one has to remember that fat evolved as a tissue where energy can be stored in the form of fatty acids to deal with periods of fasting. However, the problem arises when the body remains in a state of nutrient excess and fat is not broken down.

The cheap and easy access to calories has led to the epidemic of obesity worldwide, and nearly 40% of the US population is obese (defined by BMI >30). Build up of unused fats causes toxicity to various tissues and enhances the risk of several age-related diseases, including Type II diabetes. Thus, a restriction of nutrients achieved by fasting is necessary to help burn fat.

Fasting elevates proteins that break down fats in the adipose tissue.

These enzymes are also responsible for the efficient function of mitochondria, the energy powerhouse of the cell. Thus fasting is a critical way to train the mitochondria so they last longer. The ability to break down fat was also necessary to derive the lifespan extension benefits of nutrient restriction. [9] Thus, fat burning is a critical outcome of fasting that can help reduce weight and stave off several diseases.

6. Fasting makes you active and helps maintain muscle mass

One of the surprising benefits of fasting is that it makes you physically active. Though not intuitive, this makes sense if one considers what one would do if they were in a forest and looking for food. The benefits of fasting on improving physical activity have been seen in different species from small nematode worms to flies and mammals, suggesting a conserved response.

Upon fasting the body uses up its glucose, then glycogen, a polymer of glucose, and then fat burning. Fasting, usually beyond 12 hours, leads to depleting glycogen stores and initiates fatty acid consumption. This switch from utilizing glycogen to utilizing fatty acids is an evolutionarily conserved trigger point where fat synthesis is replaced by fat utilization.

Loss of muscle mass with age has been observed across species and is known as sarcopenia in humans.

Though one associates fasting with wasting away of the tissues, counterintuitively partial restriction of nutrients is associated with muscle mass maintenance in mice and humans. A likely reason for this is that though there is a lack of nutrients for different tissues during fasting, muscle mass maintenance is prioritised as the organism is physically active.

Thus decline in muscle mass during normal aging is restricted with fasting. Fasting, therefore, maintains muscle performance and keeps you active [10].

7. Fasting improves mental health

Learning and memory were improved in mice that were on a fasting diet. [11] Short-term fasting also improves memory in humans. Like improvement in physical activity, memory improvement is a likely adaptation to optimize the organism to obtain food under conditions of food scarcity.

Fasting also improves the dopamine levels that help you maintain a positive attitude and confidence [12].

Increasing dopamine also delays

the risk of ‘Parkinson’s disease.

Fasting also helps avoid food coma keeping your head clear. By adhering to better eating habits, one can fight off addictive behaviours with ease, boosting self-control.

Food abundance also impairs cognition and increases the risk of neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and dementia. Fasting stimulates brain repair pathways keeping age-related brain disorders at bay.

8. Fasting improves gut health

Fasting enhances digestion and improves overall gut health. Inflammatory bowel disease (IBD) is a blanket term used for the gastrointestinal tract’s chronic inflammatory diseases.

The incidence of IBDs, like ulcerative colitis, is increasing. Intermittent fasting suppressed the inflammatory response in the gut and alleviated the symptoms of IBD colitis-induced mice. [13].

Furthermore, fasting also reduces the gut’s leakiness, which increases with age and in IBD in fly and mouse models. The intestinal cells are some of the most active cells in our body, one of the first tissues that come in contact with food. One idea is that fasting allows the intestinal cells to repair and replenish, thus improving gut health.

9. Fasting enhances repair and reduces toxins

Loss of DNA and protein damage repair is a hallmark of aging. Fasting increases the repair and maintenance processes in cells. [14]

In a 30-day study assessing intermittent fasting effects in humans, key regulatory proteins from the DNA repair pathway were induced [15].

Autophagy is a process of breakdown of old, unwanted, or damaged components of our body by our enzymes. This serves two purposes – removing unwanted or toxic proteins and ready availability of the simple broken down amino acids to build newer proteins and protein repair.

Fasting and caloric restriction upregulate autophagy, and thus, help in protein repair. [16]

10. Fasting is cost-efficient and accessible to all

Fasting is perhaps the most cost-efficient alternative. It can save an individual a significant sum of money by reducing food costs and extending a healthy lifespan, thus delaying retirement age and avoiding expensive medical bills that accompany the chronic age-related disease.

Fasting can be incorporated easily into a busy lifestyle.

Fasting is the least time-consuming alternative for healthy aging. Fasting can be practised anytime and anywhere.  Most weight loss programs involve an initial period of caloric restriction and eating the right kind and amount of food.

……..

Individual differences exist, and everyone may not derive the same or equal benefits from fasting. Nevertheless, the evidence is overwhelming in its favor to provide multiple benefits to individuals who practice it.

With the short-term benefits of fasting, including improved physical activity, memory enhancement, improved digestion, and improved insulin sensitivity, there are good reasons to adopt some form of fasting in your lifestyle.

Furthermore, the long-term benefits of improved cardiovascular and mental health that can help stave off major age-related diseases provide more compelling reasons to stick to a fasting regime that works for you.

In summary, though fasting may not be precisely the promised elixir of life, it remains the best option to date.

At the same time, scientists make progress in, slowing the burden of diseases. That is why several thought leaders in the field of aging and diabetes preach and practice it themselves.

It is always important to visit a professional for a diet consultation before starting one. If you have any comments, please mention them in the section below.

Read more: Fasting for a healthy mind: 9 reasons, why it is a no-brainer!

Written by Shubhankar Kulkarni, Ph.D. and Pankaj Kapahi, Ph.D.

Banner image courtesy: The Fountain of Youth, 1546 painting by Lucas Cranach the Elder

References

1.       McCay CM, Crowell MF, Maynard LA. The Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size. J Nutr [Internet]. 1935 Jul 1;10(1):63–79. Available from: https://academic.oup.com/jn/article/10/1/63/4725662

2.        Hwangbo D-S, Lee H-Y, Abozaid LS, Min K-J. Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms. Nutrients [Internet]. 2020 Apr 24;12(4):1194. Available from: https://www.mdpi.com/2072-6643/12/4/1194

3.        Brandhorst S, Longo VD. Protein Quantity and Source, Fasting-Mimicking Diets, and Longevity. Adv Nutr [Internet]. 2019 Nov 1;10(Supplement_4):S340–50. Available from: https://academic.oup.com/advances/article/10/Supplement_4/S340/5624067

4.        Berrington de Gonzalez A, Hartge P, Cerhan JR, Flint AJ, Hannan L, MacInnis RJ, et al. Body-Mass Index and Mortality among 1.46 Million White Adults. N Engl J Med [Internet]. 2010 Dec 2;363(23):2211–9. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa1000367

5.        Mattson MP. An Evolutionary Perspective on Why Food Overconsumption Impairs Cognition. Trends Cogn Sci [Internet]. 2019 Mar;23(3):200–12. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1364661319300208

6.        Cho Y, Hong N, Kim K, Cho S, Lee M, Lee Y, et al. The Effectiveness of Intermittent Fasting to Reduce Body Mass Index and Glucose Metabolism: A Systematic Review and Meta-Analysis. J Clin Med [Internet]. 2019 Oct 9;8(10):1645. Available from: https://www.mdpi.com/2077-0383/8/10/1645

7.        Nencioni A, Caffa I, Cortellino S, Longo VD. Fasting and cancer: molecular mechanisms and clinical application. Nat Rev Cancer [Internet]. 2018 Nov 16;18(11):707–19. Available from: http://www.nature.com/articles/s41568-018-0061-0

8.        de Groot S, Pijl H, Hoeven  van der, M. JJ, Kroep JR. Effects of short-term fasting on cancer treatment. J Exp Clin Cancer Res [Internet]. 2019 Dec 22;38(1):209. Available from: https://jeccr.biomedcentral.com/articles/10.1186/s13046-019-1189-9

9.        Katewa SD, Demontis F, Kolipinski M, Hubbard A, Gill MS, Perrimon N, et al. Intramyocellular Fatty-Acid Metabolism Plays a Critical Role in Mediating Responses to Dietary Restriction in Drosophila melanogaster. Cell Metab [Internet]. 2012 Jul;16(1):97–103. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1550413112002422

10.      Anton SD, Moehl K, Donahoo WT, Marosi K, Lee SA, Mainous AG, et al. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity [Internet]. 2018 Feb;26(2):254–68. Available from: http://doi.wiley.com/10.1002/oby.22065

11.      Li L, Wang Z, Zuo Z. Chronic Intermittent Fasting Improves Cognitive Functions and Brain Structures in Mice. Xie Z, editor. PLoS One [Internet]. 2013 Jun 3;8(6):e66069. Available from: https://dx.plos.org/10.1371/journal.pone.0066069

12.      Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev [Internet]. 2017 Oct;39:46–58. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1568163716302513

13.      Zhang X, Zou Q, Zhao B, Zhang J, Zhao W, Li Y, et al. Effects of alternate-day fasting, time-restricted fasting and intermittent energy restriction DSS-induced on colitis and behavioral disorders. Redox Biol [Internet]. 2020 May;32:101535. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2213231720303840

14.      de Groot S, Lugtenberg RT, Cohen D, Welters MJP, Ehsan I, Vreeswijk MPG, et al. Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. Nat Commun [Internet]. 2020 Dec 23;11(1):3083. Available from: http://www.nature.com/articles/s41467-020-16138-3

15.      Mindikoglu AL, Abdulsada MM, Jain A, Choi JM, Jalal PK, Devaraj S, et al. Intermittent fasting from dawn to sunset for 30 consecutive days is associated with anticancer proteomic signature and upregulates key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system. J Proteomics [Internet]. 2020 Apr;217:103645. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1874391920300130

16.      Bagherniya M, Butler AE, Barreto GE, Sahebkar A. The effect of fasting or calorie restriction on autophagy induction: A review of the literature. Ageing Res Rev [Internet]. 2018 Nov;47:183–97. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1568163718301478

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