Cellular energy: breathing, metabolism, and the microbiome

I work as a chief physician in an integrative medicine clinic. As part of my activities, I perform preliminary diagnoses of newly arrived patients and accept several patients daily. With every patient, we start with a detailed health interview and ask about their current symptoms. Health complaints vary; people have different diagnoses, family health histories, and medications. However, one theme is prevalent: 8 out of 10 patients suffering from chronic fatigue and low energy levels. Some feel weak and sleepy during the day, some must take naps during the day, and others have no energy even after sleep. These are long-term symptoms, often lasting for years. Usually, people mitigate them with multiple supplements and stimulants, but the effects are not last. This theme is so common that it is important to dig down to the roots, understand the real reasons for low energy levels, and offer general non-pharmaceutical solutions.  Let us start at the beginning. Most of our energy is produced via cellular respiration from the food we eat (carbohydrates, proteins, and fats) in mitochondria in the form of Adenosine Triphosphate (ATP) molecules. This process consists of 4 stages and is very efficient: 38 molecules of ATP are produced from one glucose (basic sugar) molecule. This amount is many times higher than what bacteria or cancer cells produced by glycolysis. Usually, we generate enough energy to carry us through the day without tiredness. Yes, there are some periods of sleepiness, usually shortly after meals and mid-day. These off-peaks are natural, temporary, and well-explained by the metabolic cycle and circadian rhythm.  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:

• There can be insufficient oxygen access in the lungs. Unless you are an advanced practitioner of kriya-yoga, your energy is totally dependent on the efficient consumption of molecular oxygen, O2, by the lung alveoli. Oxygen is bound to hemoglobin in our red blood cells (RBCs, or erythrocytes) and transported throughout all organ systems. We need good unscarred lungs (I hope you don't smoke or vape) and intact RBCs. This correlation is very straightforward. Patients with a lot of lung fibrous tissue (usually due to age, years of smoking, and lack of exercise) are often chronically tired. The good news is that lung tissues regenerate at any age. Its function is greatly supported by endurance exercises such as walking, jogging, or swimming, breathing programs such as pranayama, energy practices such as Qigong, and other methods. In our clinic, we apply a simple system of breathing exercises that we practice on the cliff over the tide waves (there is an additional benefit of breathing sea water in nano-drops formed by crashing waves).
• The health of red blood cells (RBCs) could have deteriorated. 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). Standard blood tests are unable to detect this damage. Typically, patients with chronic fatigue syndrome have a 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 selected IV drips can restore their shape and function in 1-2 days. Sometimes, however, the damaged RBCs are persistent in the blood, and the patients continue to feel tired due to tissue hypoxia. In such cases, the damaged RBCs must be eliminated throughout the system, and a new healthy generation is produced from stem cells in the red bone marrow. We accelerate the process with IV laser therapy to induce stem cells and activate apoptosis, or programmed cell death, to speed the elimination of the damaged RBCs. This process usually takes 7-10 days. We know that it is completed when patients wake up one day with a broad smile and say that the air was remarkably crisp that night. 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.  

Fig. 1. Cellular energy in blood microscopy.

1. Red blood cells (RBCs), or erythrocytes. 1. Normal RBCs; 2. Deformed RBCs, carry less oxygen. 1000X magnification, phase contrast.
2. 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)

• There could be issues with mitochondrial health. Our mitochondria being our main ATP factory, their well-being is key to our energy production level (Fig.2). Virtually all chronic conditions impact the mitochondria. Those cells have their own genome, and their mutations are inheritable, although mitochondrial genetic diseases are rare, affecting some 1 in 5000 individuals. More frequently, mitochondria's failures to produce enough energy are not hereditary and are associated with acquired conditions such as diabetes, muscular dystrophy, neurodegenerative diseases, high levels of systemic inflammation, cancer, and more. Mitochondria have an electric potential of 160 mV on their membrane, and energy production depends on this charge. Once the membrane loses this charge, energy production drops. There are also many compounds and metabolites inhibiting mitochondria's enzymes. A remnant of ancient bacteria, the mitochondria are also sensitive to direct signaling by the human microbiome, particularly from the gut. The good news is that damage to mitochondria health is reversible, and to some extent, they can be recharged, just like Tesla batteries. Red light therapy or laser can do this in a few procedures. 

Fig. 2. Human mitochondrion, the energy-producing cellular organelle.  There is a potential of 160mV between 2 layers of membrane

• Our metabolism could be off. ATP is produced by oxidizing pyruvate (coming from carbohydrates), amino acids (from proteins), and fatty acids (fat). The efficiency of this process is directly related to our diet and the 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 in the "Western diet", consumption of modified food (for example, food containing hormones, antibiotics, and glyphosates found in many products), irregular meals, etc. Metabolic failures disrupt the "supply chain" for mitochondria energy stations, and, just in the global economy during a covid pandemic, they cause a sharp decline in ATP production. How to avoid it? Well, you know the drill: eat only when you feel hungry, add low-calorie fasting days to your calendar, slow your metabolism by reducing your intake of dead animal protein, and follow the rules of intermittent fasting. In our experience, following these simple rules help immensely.
• Our microbiome. A former bacterium themselves, mitochondria are part of our global microbiome, a universe of microorganisms that outnumber human cells 100:1 in our own body. As it became recently known, to a large extent, our health, tastes, mood, and even social interactions are dependent on our microbiome composition and communal metabolism. The bad microbes in the gut, intestine, and blood (for example, filamentous fungi, candida yeast, klebsiella, and borrelia) can directly drain our energy, make us eat more sugars, and signal mitochondria to slow down ATP production. Dysbiosis of the gut microbiota and mitochondrial dysfunction are both associated with chronic intestinal inflammation, and this condition greatly diminishes mitochondrial enzymatic processes. How to balance the microbiome? The short answer is to supply gut microbes with their favorite food at the right time. The longer story deserves a separate blog.
• Systemic chronic inflammation (SCI) could be present in the body. By now, it is well understood that chronic inflammation is the basis for most chronic conditions, from cardiovascular diseases to diabetes and cancer. Mitochondrial dysfunction plays a significant role in establishing the 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.

These are the main factors that regulate our energy production. Deficiency at these levels can severely impact ATP levels 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 cleansing and lymphatic system detox decrease the level of systemic information and help to restore enzymatic complexes on the mitochondria membrane. In the long run, changing habits and diet restores a healthy gut microbiome, which can sustainably maintain high energy levels in mitochondria. Physical activity, walking, and breathing exercises help a lot: 30-60 min of physical activity per day substantially increases our energy production.                      By Yuri Nikolsky, Ph.D. Santa Maria Holistic Health Retreat