Intermittent fasting and interval hypoxic training for activation of adaptive reserves of the body, prevention and treatment of degenerative brain diseases

Degenerative brain diseases (DBD) and other cognitive dysfunctions may appear due to the depletion of adaptive reserves as a result of aging, stress, depression, and other pathological processes (inflammation, malignant neoplasms). The depletion of the adaptive reserves leads to disordering accurate, appropriate signaling in the brain, between the brain and the body, as well as disorders at the levels of the organs, cells and molecules.

The body's adaptive reserves ultimately determine the tolerability or the resistance to various degrees of hypoxia, which accompanies stress, trauma, depression, inflammation, and aging. Oxygen is the most important and fastest regulator of metabolism.

The fundamental concept is as follows: optimal health is activated and stimulated by intermittent stimulation, i.e. moderate functional loads [1, 2]. We offer practical programs, which combine two non-pharmacological natural methods of activation therapy, training aimed at improving the adaptive reserve of the human body: intermittent fasting treatment (IFT) and interval hypoxic training (IHT).

IFT is a diet treatment that implies periodic fasting with special preliminary preparation and control of hunger sensation, sometimes with intake of some vitamins, trace chemical elements and electrolytes. The most often used intermittent fasting regimen in our practice is a 2-3-5-day fasting regimen repeated 3-2-1 times a month.

IHT is a way to increase the organism's nonspecific resistance by adapting to hypoxia. Adaptation develops when breathing with a hypoxic gas mixture (10-13% oxygen and about 87-90% nitrogen) through a mask (at normal atmospheric pressure) in an intermittent mode: breathing for 4-5 minutes with a hypoxic gas mixture with a break of 4-3 minutes (breathing room air corresponds to the sea level), that is, 4/4 or 5/3, 6-7 cycles, with session duration of 40 - 55 minutes. The therapeutic effect of IHT is achieved by a repeated, multiple (5-7 times) decrease in oxygen saturation (SpO2) from 94-99% to 80-86% within one session.

The main measures for the prevention and rehabilitation of degenerative diseases should be to support the biogenesis of mitochondria and their efficiency as well as reduce misfolding of proteins in cells. Mitochondria do not operate efficiently and generate more superoxides, when they are supplied with large amounts of glucose and oxygen.

Our goal is to maintain the maximum (optimal?) efficiency of the mitochondrial function at the cellular and molecular levels. This is achieved by quantitatively changing delivery of oxygen and glucose that is provided with IFT and IHT.

Pathological neural networks in the brain differ biochemically from the healthy tissue in an increased amount of lactic acid. The capability of IHT (similar to breathing at high altitude) of removing and reducing the content of lactic acid in the tissues and the organs, including the brain, leads to the elimination of pathological neural networks in the brain. This explains the "spontaneous" recovery in patients with epilepsy as well as the rapid essential improvement in the condition of patients after heart attacks and strokes.

Considering any disease (and its resistance to treatment) as the appearance and building-up of some pathological neural networks or pathological dominants in the brain (A.A. Ukhtomsky), which are supported by some biochemical changes (shifts in the content of lactic acid, norepinephrine), IHT can be evaluated as a unique treatment method.

IHT may exert its influence on the key links in the pathogenesis of DBD like the Ca2+ homeostasis disorders, oxidative stress, impaired nitric oxide (NO) synthesis, excitotoxicity that inevitably leads to an ischemic cascade and a cerebrovascular accident. The protective mechanisms of adaptation to hypoxia may be associated with the limitation of oxidative stress in the hippocampus, the limitation in the decrease in the NO production induced by b-amyloid, and the increase in the density of the vasculature in the brain [3].

IFT stimulates the development of three major protective and therapeutic benefits for the brain: increased autophagy [4], increased levels of brain-derived neurotrophic factor (BDNF) [5], and ketosis [2]. Ketone bodies such as hydrox butyrate are neuroprotective.

IFT may protect neurons from oxidative and metabolic stress in animal models of Parkinson's disease [5], Alzheimer's disease [6], and stroke [7]. The activity of cytokines as a result of IFT has a neuroprotective effect. The leptin and adiponectin levels also mediate neuroprotective effects. The sirtuin family of genes and corresponding proteins, which appear due to IFT, have a wide range of effects that improve health and longevity [9, 10].

The fasting treatment triggers the mechanisms responsible for a sparing energy by the cell, since it leads to the activation of AMP-dependent kinase - AMPK. As a result of the AMPK activation, the processes of maintaining a sufficient number of stem cells in tissues are activated, and neoplasms are inhibited. Restorative nutrition is an important stage in the treatment procedure. To ensure maximum positive results, it is important to design an individual IFT program with a targeted treatment diet.

It is possible to achieve a significant reduction in stress of the endoplasmic reticulum, increase the antitoxic protection of the cell, and suppress inflammation with an addition of certain food to 19 Cardiometry, Issue 24, November 2022

activate Nrf2 and the transcription factor PGC-1a, which contribute to the restoration of mitochondria.

By combining these two methods of intermittent stimulation, we can synchronize the brain functions in a faster and more efficient manner and increase the brain's ability for plasticity and self-restoration.

Coordination of both methods is essential in order to obtain the maximum long-term favorable effects. The duration, the rate of breathing cycles and the amount of oxygen (determining the intensity of episodes/cycles of hypoxia), on the one hand, and the duration of fasting with a restorative diet, on the other hand, are important factors.

In our presentation, we introduce data from our 35- year experience in fasting treatment for in- and outpatients and our 25- year experience in IHT. These results support the idea that the selected programs make a perfect combination to treat and prevent DBD. In our opinion, this strategy can provide a practical breakthrough in clinical care and the research approach to these diseases.