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Cellular energy: coupling breathing, metabolism and microbiome

With every patient, we start with a detailed health interview and ask about their current symptoms. Health complaints vary a lot; people have different diagnoses, family health histories and medications. However, one theme is very common: 8 out of 10 of our patients suffer from chronic fatigue and low energy level. Some feel weak and sleepy part of day, some have to sleep during the day, others have no energy even when they wake up. These are long term symptoms, often lasting for years. Usually, people use multiple supplements and stimulants, but the effects are not long lasting. The theme is so common, that it is important to dig down to the roots and understand the real reasons for low energy levels.
Let us start at the beginning. Our energy is mostly produced via cellular respiration from the food we eat (carbohydrates, proteins and fats) in mitochondria in a form of Adenosine Triphosphate (ATP) molecules. This process consists of 4 stages and is very efficient: 38 molecules of ATP are produced from one molecule of the basic sugar, glucose, many times more than bacteria or cancer cells produce by glycolysis. Normally, we generate enough energy to carry us through the day without tiredness. Yes, there are some periods of feeling sleepy, usually shortly after meals and in the mid-day. These off-peaks are natural, temporary and well-explained by metabolic cycle and circadian rythm.
Chronic fatigue is a very different story. Let's consider what can go wrong in energy production for so many people? Quite a few things:
  • Sufficient oxygen access in lungs. Unless you are an advanced practitioner of kriya-yoga, our energy is absolutely dependent on efficient consumption of molecular oxygen, O2 by the lung alveoli. There, oxygen is bound to hemoglobin in our red blood cells (RBCs, or erythrocytes) and transported in all organ systems. Naturally, we need to have good unscarred lungs (hope you don't smoke or vape) and intact RBCs. This is very straightforward. Patients with a lot of fibrous tissue in lungs (which is usually due to age, years of smoking and lack of exercise) are often chronically tired. The good news is that lungs tissues regenerate at any age. Its function is greatly supported by endurance exercises such as walking, jogging or swimming and by breathing programs, such as pranayama, Qigong or other systems. At Santa Maria, we apply a simple system of breathing exercises which we practice on the cliff over the tide waves (there is an additional benefit of breathing sea water in nano-drops which are formed by wave crashing).
  • The health of red blood cells (RBCs). Erythrocytes are quite fragile and sensitive to environmental stress. During blood microscopy of people with low energy (best seen in 1000X magnification, phase contrast objective), we often see RBCs damaged, misshaped or aggregated together in long stacks (rouleaux) (Fig.1). This damage is not seen on standard blood tests. Typically, patients with chronic fatigue syndrome have normal count of RBCs, levels of hemoglobin, hematocrit and free iron and their doctors are puzzled. In many cases, the morphological damage to RBCs is reversible and their shape and function can be restored by selected IV drips in 1-2 days. Sometimes, however, the damaged RBCs are persistent in blood, and the patients continue to feel tired due to tissue hypoxia. In such cases, the damaged RBCs have to be eliminated through the system and the new healthy generation produced from stem cells in red bone marrow. We accelerate the process with IV laser therapy to induce stem cells and activate apoptosis, or programmed cell death, to speed elimination of the damaged RBCs. This process usually takes 7-10 days and we know that it is completed when patients wake up one day with a broad smile and say that the air this night was particularly crisp. We don't even need to look at their blood. We know we will see happy unaggregated donut-shaped erythrocytes and the energy is back.
Cellular energy in blood microscopy
Fig. 1. Cellular energy in blood microscopy.
A. Red blood cells 9RBCs), or erythrocytes . 1. Normal RBCs; 2.Deformed RBCs, which care less oxygen. 1000X magnification, phase contrast.
B. Mitochondrial health-related patterns in dry blood.
1.Normal mitochondrial energy: 100% RBCs; 2. very low mitochondrial energy: 20% RBCs / 80% PPPs (plasma protein pools)
Human mitochondrion, the energy producing cellular organelle
Fig. 2. Human mitochondrion, the energy producing cellular organelle.
 There is a potential of 160mV between 2 layers of membrane
  • Mitochondrial health. As our main ATP factory, our mitochondria well-being is key to our energy production level (Fig.2). Mitochondria are impacted in virtually all chronic conditions. Mitochondria have their own genome and its mutations are inheritable, although genetic mitochondrial diseases are rare, affecting some 1:5000 individuals. More frequently, mitochondria's failures to produce enough energy are not genetic and associated with cancer, diabetes, muscular dystrophy, neurodegenerative diseases, high level of systemic inflammation and more. Mitochondria has an electric potential of 160 mV on their membrane, and energy production is dependent on this charge. Once the membrane losses this charge, the energy production drops. There are also many compounds and metabolites inhibiting mitochondria's enzymes. Being a remnant of ancient bacteria, mitochondria are also sensitive to direct signaling by human microbiome, particularly from gut. The good news is that mitochondria health is reversable and to some extend they can be re-charged, just as Tesla batteries. Red light therapy or laser can do this in few procedures.
  • Mitochondrial health. As our main ATP factory, our mitochondria well-being is key to our energy production level (Fig.2). Mitochondria are impacted in virtually all chronic conditions. Mitochondria have their own genome and its mutations are inheritable, although genetic mitochondrial diseases are rare, affecting some 1:5000 individuals. More frequently, mitochondria's failures to produce enough energy are not genetic and associated with cancer, diabetes, muscular dystrophy, neurodegenerative diseases, high level of systemic inflammation and more. Mitochondria has an electric potential of 160 mV on their membrane, and energy production is dependent on this charge. Once the membrane losses this charge, the energy production drops. There are also many compounds and metabolites inhibiting mitochondria's enzymes. Being a remnant of ancient bacteria, mitochondria are also sensitive to direct signaling by human microbiome, particularly from gut. The good news is that mitochondria health is reversable and to some extend they can be re-charged, just as Tesla batteries. Red light therapy or laser can do this in few procedures.
Human mitochondrion, the energy producing cellular organelle
Fig. 2. Human mitochondrion, the energy producing cellular organelle.
 There is a potential of 160mV between 2 layers of membrane
  • Our metabolism. ATP is produced by oxidizing pyruvate (coming from carbohydrates), amino acids (from proteins) and fatty acids (fat). The efficiency of this production is directly related to our diet and ability of our metabolism to fully process food. Our metabolic system is robust, but it can be negatively affected by unhealthy or excessive food intake, disbalances of "Western diet", consumption of modified food (for example with hormones, antibiotics, glyphosates found in many products), irregular meals etc. Metabolic failures disrupt "supply chain" for mitochondria energy stations, and, just in global economy during covid pandemic, they cause sharp decline in ATP production. How to avoid it? Well, you know the drill: eat only when you feel hungry, make breaks as low calories days, slow your metabolism by reducing animal protein in died, follow the rules of intermittent fasting. In our experience, following these simple rules help immensely
  • Our microbiome. A former bacteria themselves, mitochondria are part of our global microbiome, a universe of microorganisms which outnumber human cells 100:1 in our own body. As it became recently known, to a large extend, our health, tastes, mood, even social interactions are dependent on our microbiome composition and communal metabolism. The wrong microbes in gut, intestine and blood (for example, filamentous fungi, candida yeast, klebsiella, borrelia) can directly drain our energy, make us eat more sugars and signal mitochondria to slow down ATP production. Both dysbiosis of the gut microbiota and mitochondrial dysfunction are associated with chronic intestinal inflammation and this condition greatly diminishes mitochondrial enzymatic processes. How to balance microbiome? The short answer is by supplying gut microbes with their favorite food in right time. The longer story deserves a separate blog
  • Systemic chronic inflammation (SCI). By now, it is well understood that the state of chronic inflammation is the basis for most chronic conditions, from cardiovascular diseases to diabetes and cancer (Fig.3). Mitochondrial disfunction plays a major role in establishing state of SCI via pro-inflammatory signaling. And vice versa, the stage of SCI impairs ATP production by reducing the TCA cycle metabolism and membrane potential.
Systemic chronic inflammation impairs energy production in mitochondria
Fig.3 Systemic chronic inflammation impairs energy production in mitochondria

Furman D. et al., Nat. Medicine, 2019
These are the main factors which regulate our energy production. Deficiency at any of these levels can severely impact ATP level and cause chronic fatigue. The good thing though is that these deficiencies are mostly reversible. In the short run, red light and laser therapy can recharge the mitochondrial electric potential. Deep blood and lymphatic system detox decrease the level of systemic information and helps to restore enzymatic complexes on mitochondria membrane. In the longer run, change of habits and diet restores healthy gut microbiome, which can sustainably maintain high energy level in mitochondria. Physical activity, walking, breathing exercises help a lot: 30-60 min of physical activity daily substantially increase our energy production.
About the author
Yuri Nikolsky
Ph.D.
Yuri is a molecular biologist, trained in military medicine (infectious diseases and epidemiology). Fifteen years of experience as an academic scientist and executive at biotech companies. Expertise in pre-clinical small molecules drug discovery, systems biology, genomics, translational medicine. Published over 70 peer-review scientific articles. Yuri is a US-certified stem cells practitioner (ISSCA). Yuri is in charge of Santa Maria technology and health programs