EpigeneticsDietIntermittent fasting

Intermittent Fasting – The ultimate medicine for improving health, reversing diseases and slowing down aging

One of the most popular health and fitness trends in the last years is intermittent fasting. Some call it a diet, others a regime, a way of living, a phenomenon and so on. If not everyone, many of us have heard this term from television, internet, maybe some famous person has been talking about it or even a friend or relative uses it. Despite all this, it is clear that Fasting is getting more and more recognized and used. 

Intermittent fasting (IF) is describing several eating patterns, all circulating over one main thing – eating no or few calories for time periods, ranging from 12 hours to several days, on a recurring basis. There are different types of IF regimes. The main and most used types are – typical intermittent fasting, time—restricted feeding, alternate day fasting, periodic fasting and religious fasting. (Table 1.) [1]

Table 1. Intermittent fasting types and their impact on health.

Note. Reprinted from Metabolic Effects of Intermittent Fasting (2017), published in Annual Review of Nutrition.

As we can see from the definition of the term IF, the word diet is not mentioned, even more, there are no restrictions on what you should eat during the ‘time’ you actually eat. That is why IF alone is a regime, not particularly a diet. Regardless that IF gained popularity in recent years, this way of eating and living is not new for mankind. Data form our ancestors and early hunter societies shows that humans evolved, while intermittently experiencing extended periods of time with no or little food. They had no chance, but to grow or catch their food and did not have the opportunity to eat 3 or more times a day, like the modern people. Fasting has been used for thousands of years as a religious and medical practice. Ancient Chinese, Greek and Roman physicians were suggesting fasting for medical reasons, back in time.[1] According to the Islamic practice, healthy adult Muslims should fast from sunrise to sunset during the holy month of Ramadan. In this religious fast fluid intake, cigarette smoking and medications are also forbidden. This fast does not require energy restriction, but with the less frequent intake of food and water, the body weight may vary. [1,2]

We, as humans are meant to eat less frequent, not the way modern society is – three times a day, plus snacks and sedentary life. A lot of the most common diseases are in some way connected with our eating habits and sedentary lifestyle – obesity, diabetes, heart problems, metabolic syndrome, even cancer and autoimmune diseases are believed to have a connection.

The main sources of energy for the cells in our bodies are glucose and fatty acids. Normally after a meal, glucose is used for energy and fat is stored as triglycerides in adipose tissue. That is what changes when we fast – we do not eat and so that energy should come from something else and that is when our body breaks down triglycerides to glycerol and fatty acids, than the liver converts these fatty acids to ketone bodies in a process called gluconeogenesis and these ketone bodies become the main source of energy for our tissues. This is called “metabolic switch” – switching from using one source of energy to another. These ketone bodies are not just a fuel, they regulate the expression and activity of many proteins, they are potent signaling molecules with major effects on cells and organs. Cells increase expression of antioxidant defenses, DNA repair, protein quality control, down regulation of inflammation, autophagy, stronger immunity in response to the repeated fasting periods. All of these changes lead to a lot of health benefits. [3]

IF helps with weight loss, prevents obesity, improves diabetic retinopathy and even reverses insulin resistance in patients with prediabetes or type 2 diabetes. The traditional population on the island of Okinawa maintain an IF regime, consuming nutrient rich sources diet and they have low rates of obesity and diabetes, as well as extreme longevity. Numerous indicators of cardiovascular health can be improved by IF, like – blood pressure, levels of high-density and low-density lipoproteins, cholesterol, glucose, insulin, IF can increase heart rate variability by increasing the parasympathetic tone. IF reduces the markers of inflammation and oxidative stress, which are connected with atherosclerosis. IF is thought to be helpful in cancer prevention and cancer treatment, because it may impair energy metabolism in cancer cells, inhibit their growth and activate transcription factors that provide protection against cancer and boost stress resistance of normal cells. Stress resistance is increased via IF in the neurons, by bolstering mitochondrial function and stimulating autophagy, DNA repair and antioxidant defenses, all of that leading to a strong evidence that fasting can delay the onset and progression of Alzheimer’s and Parkinson’s disease. Interestingly, people with asthma, who start IF, report that over a 2 months period they not only lost weight, but asthma symptoms and airway resistance were relieved. Autoimmune disease can be improved by starting IF, two pilot studies with multiple sclerosis (an autoimmune disorder characterized by axon demyelination and neuronal degeneration in the central nervous system) showed that the symptoms were reduces in a period of 2 months. [3]

As mentioned above, fasting and the metabolic switch that it leads to can improve and maintain health and longevity. Aging is a time-dependent and progressive decline in functional status, characterized by remodeling of epigenetic patterns which ultimately results in death. Main role in modulating the epigenome plays the nutrition and a lot of data shows that diet changes can modify epigenome mechanisms associated with aging. Under IF, age related changes are profoundly delayed by promoting DNA methylation and affecting histone modification, leading to possibly increased health and lifespan. [4]

Fasting for sure has numerous health benefits, although we do not fully understand the specific mechanisms yet. It may be a promising way to lose weight and improve overall health. Even a single fasting interval can reduce the concentration of many biomarkers like insulin and glucose. [2,3] The numerous benefits of IF are proved by studies on mice and rats, some of them are found in human studies, which suggests that IF can protect from and reverse diseases like metabolic syndrome, diabetes, cardiovascular problems, even the recent small trials showed a significant results in people with multiple sclerosis and other chronic age related disorders.[5]

Recently, as fasting has been studied more and more, physicians are going into details about the mechanisms that it changes in our bodies, as well as its overall impact on our health. Although more studies need to be done, we could say that the benefits of IF are certainly plenty and different types of people could give it a try and benefit from it.

Strahil Vasilev – Medical University, Sofia

[1] – D anton et al.. (2018). Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity: The Journal of The Obesity Society, 26(2), 254-268.
Link to the full article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783752/

[2] – E patterson, R & D sears, D. (2017). Metabolic Effects of Intermittent Fasting. Annual Reviews, 37(3), 371-393.
Link to the full article: https://www.annualreviews.org/doi/10.1146/annurev-nutr-071816-064634?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed

[3] – De cabo, R & P mattson, M. (2019). Effects of Intermittent Fasting on Health, Aging, and Disease. The New England Journal of Medicine, 381(26), 2541 – 2551.
Link to the full article: https://www.gwern.net/docs/longevity/2019-decabo.pdf

[4] – Genesous et al.. (2019). The Impact of Caloric Restriction on the Epigenetic Signatures of Aging. International Journal of Molecular Sciences, 20(8), 2022.
Link to the full article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515465/

[5] – Matsson , M, Harvie, M & D longo , V. (2017). Impact of intermittent fasting on health and disease processes. Elsevier, 39(10), 46-58.
Link to the full article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411330/

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