Chronic Disease: A Bioenergetic Paradigm
INTRODUCTION
What are chronic diseases? What distinguishes multiple sclerosis from a broken leg? Both involve damage to the organism, but while most acute diseases like fractures or cuts tend to either kill or resolve, chronic disease is usually persistent. Currently, there is no overarching medical framework that tries to explain the general features of chronic disease, and therefore also provide universal therapeutic intervention points that are independent of the particular disease.
This lack of a unifying paradigm reveals the particularist and specialist-driven aspect of modern medicine, which for the most part ignores whole-organism interactions. When these cross-organ effects cannot be ignored they are usually renamed in “medicalese” and considered explained. For example, both hepato-renal syndrome and hepatic encephalopathy involve the liver as the starting point, but the disease endpoint is as distant as the kidneys or the brain. They are complex phenomena involving nitric oxide, and endotoxin, among others. A more sophisticated renaming achieves nothing except to confuse already difficult concepts. We have to take the opposite approach, instead of unnecessary complexity, let’s aim for clarifying generalities.
I believe, based on my understanding of the groundbreaking work by Raymond Peat, PhD, that chronic illness has three fundamental pillars which are interrelated and maintained by positive (vicious cycle) feedback loops. These pillars are:
- Metabolism and energy production
- Inflammation
- Over-excitation
This paradigm is meant to explain how chronic disease is maintained. The related question of how chronic disease starts in the first place will be treated in another article dealing with the general nature of adaptive stress systems.
METABOLISM
Perhaps the most fundamental feature of chronic disease is inadequate energy production. Electron flow is arrested, the complete oxidation of glucose to CO2 is interrupted, and lactic acid is generated (sometimes in massive quantities). This lack of energy flow lowers the ordering of the cell and diminishes its adaptive capacity. With a lowered adaptive capacity, stimuli, and harmful influences activate cellular stress systems. These systems enable the cell to survive but at a steep price. A “metabolic scar” remains in the subtle structure of the cell, further hindering electron flow. Here we find our first stress system vicious cycle, but we will meet many more. They are characteristic of chronic disease.
The most fundamental mediator of lowered metabolism is, I believe, estrogen. It has immediate effects on a cell, causing it to take up water and swell while activating glycolytic processes and increasing lactate dehydrogenase. These effects are independent of any receptor and happen because of estrogen’s effect on the cell structure, acting as a “dissolving” and de-structuring agent.
INFLAMMATION
It is an empirical fact that most chronic disease involves some level of inflammation. We could stop there, but inflammation is a topic that deserves close attention. The idea that inflammation could happen without a concurrent infection, “sterile inflammation” was for many years denied. The immune system was conceived only as a destroyer. The work of immunologists like Janeway and Polly Matzinger began to change this incomplete view of the immune system. Its main function was now seen as the maintenance of organism integrity, and pathogen elimination was only one of the ways this was achieved. It is not pathogens per se that activate the immune system, but tissue damage and destruction.
Almost every cell in the body can produce inflammatory mediators. When tissue damage happens, neighboring cells start secreting these mediators to recruit the immune system. The first step is tissue repair and regeneration, which can occur without any appreciable inflammation. Only when tissue repair fails, or phagocytic cells like macrophages are overwhelmed by too much cellular waste, does inflammation properly begin to happen. This means that inflammation is not the main way that the immune system operates. It happens only once constructive repair has failed, usually because of a lack of energy production. The problem is that almost all inflammatory mediators keep a cell stuck in a low-energy, stressed state. Another vicious cycle.
Inflammation also activates related processes like clotting and platelet activation. From an evolutionary point of view, it makes sense. Most inflammation was due to a pathogen entering a wound, so it makes sense that the immune system and the blood clotting system would be closely related. Excess clotting increases the viscosity of the blood, can completely block capillaries and in general lowers tissue oxygenation, leading to a switch to the glycolytic-lactic acid metabolism.
OVER-STIMULATION
All cells can respond to stimuli. Irritability is one of the most fundamental features of life. In general, the more energy production a cell has, the more it can respond to more subtle stimuli. Stimulation involves a temporary collapse of cell order and the influx of sodium and calcium into the cell. To re-establish the non-excited resting state energy needs to be expended. If the energetic capacity of the cell is lower it will remain stuck in a pseudo-excited state. This state makes the cell more vulnerable to stressors and also reduces the capacity to produce energy by total oxidation of glucose. Until the energetic production is increased, or the cell is protected from excess excitation this state will maintain itself.
Stuck in such a state, the cell secretes inflammatory mediators and is unable to fully relax. This absence of restorative relaxation means that it will not be able to respond to other stimuli correctly. It may not respond at all when it should, or respond inappropriately.
AN EXAMPLE OF PARADIGM APPLICATION: CHRONIC HEART FAILURE
An example of how this paradigm can be applied to the understanding of a devastating chronic disease is heart failure. Fundamentally chronic heart failure requires a reduced energetic output by cardiac muscle cells. How and why this failure is established in the first place will be dealt with in a future article, for now, it will have to be considered as an empirical fact.
A reduced energy output means that increased demands on the heart to beat faster or stronger will be more stressful than normal. The heart will compensate by activating glycolytic processes and other stress systems. To get the heart to contract appropriately the body will have to secrete increasing amounts of adrenaline, which can greatly increase intracellular calcium. This calcium is the main signal and mechanism for heart cell contraction, but because its clearing requires energy, the cell will tend to have chronically elevated levels of calcium and be unable to be in a fully relaxed state. The failure to relax means that subsequent contractions will be inefficient.
If the inefficiency of the heart comes to a point where its reduced output starts to affect its blood flow, a part of the heart that is subjected to excess demands will become acutely hypoxic and in severe cases die. Regardless of whether the cells die massively and a necrotic zone is established, or if it only happens to isolated cells, tissue damage is produced. This damage tends to increase inflammation in the cardiac, but also pericardial zones. The inflammation reduces the energetic efficiency of the myocardial cells further, leading to more excess glycolysis, over-production of lactic acid, and reliance on fatty acid oxidation as an alternative energy source.
This process is self-maintaining unless counteracting measures are taken before tissue damage is too severe and cardiac scar tissue forms. Of course, even scar tissue can be replaced with functional heart cells, but it is not an easy procedure and requires a potentially complex intervention.
UNIVERSAL THERAPEUTIC INTERVENTIONS
The fact that all chronic disease is characterized by these three pillars allows us to intervene in positive ways. Any therapeutic program should be viewed through the lens of the blockage of the many vicious cycles and on the promotion of the opposite three processes: 1) high energy production, 2) low inflammation, and 3) adequate inhibition and stimulation. There are many substances like hormones, vitamins, minerals, drugs, research chemicals, and supplements (even some herbs) that can achieve one or more of these goals. Finding an adequate combination (along with lifestyle changes) that is appropriate for the context of each person will go a long way in reversing chronic disease.
IN CONCLUSION
Lowered energy production, increased inflammation, and over-excitation are deeply connected by positive feedback cycles that serve to maintain them in an organism. Together they produce a “sickness field” (a concept I got from Georgi Dinkov) that is a whole organism phenomenon, manifesting outwardly in concrete chronic disease. Knowledge about how this sickness field works gives us ways in which it can be opposed and health re-established.