Welcome back! This is Part II of our 3-part series on systems medicine.
Hopefully you’ve had a chance to read Part I. If you haven’t, you’ll want to do so before proceeding here.
As we learned in Part I, understanding metabolism and how metabolic function influences systemic function is of paramount importance to long-term health. We also learned that the neuroendocrine system, utilizing the language of metabolism, is heavily implicated in the pathophysiology of chronic disease. If we could travel back in time and gift our past selves and family members with this valuable knowledge of metabolic health, we may have been spared much of the hardship of the chronic illness or imbalances we find ourselves facing today. Regardless, even without our time machine, there is still a great deal we can do to repair our bodies when they’ve begun to break down.
The neuroendocrine system, or stress-response system, greatly influences all cellular processes, including inflammation, weight management, hypersensitivities (including food sensitivities), blood sugar balance, hormonal balance, cognitive function, and nearly every other function of the body (6). When the neuroendocrine system is impacted by metabolic dysregulation, the results can be devastating and far-reaching. Because the neuroendocrine system may attempt to compensate for lost function or dysregulation in some predictable ways, it is useful to begin to formulate an appropriate term for this dysregulation tendency. Some have suggested “allostatic compensation” (4), though this may be inadequate. Advanced metabolic dysregulation that may lead to death in many cases has been termed “metabolic decompensation” has been documented in many cases of Inborn Errors of Metabolism (IEM), which, as we discussed earlier, are among the more well-studied genetic diseases affecting very specific locations in the metabolic superhighway (33). Metabolic decompensation and its relationship to the stress response system has been documented early in the literature (34). But first, we must understand a bit more about what is meant by the word “stress”.
Stress: What it Really is
Since imbalances in the body, including both relatively mild and more advanced stages of chronic illness, will involve the stress-response system in many ways, it is important to understand what stress itself is.
Stressors, beginning in utero and continuing throughout life, can come in many forms. Stress is itself simply a pressure applied to an object (or, in our case, a system). When you think about stress, I want you to automatically think metabolic stress, since ALL stress is interpreted via the language of these metabolic superhighways. This means that stress can originate from “external” stressors - such as being chased by a tiger/angry boss, shivering in the cold, or eating food you didn’t tolerate well - but will ultimately be internally managed and interpreted by the body’s physical metabolic system. In this way, we can say all stress is ultimately physical. This is why the “emotional pain” of an argument with a loved one is actually a physical pain and can and does cause physical symptoms. This is also why emotions ought to be considered not only as causative physical agents in systemic illness or imbalance, but as symptoms of deeper systemic imbalance as well.
Some stress is healthy, necessary, and important. An example of this is the metabolic pressure applied early in life as our immune system develops through encountering foreign antigens in our environment. The immune system is “primed” through specific forms of immunological pressures or stressors that help educate it about what dangers to look out for later in life. We can also build healthy amounts of muscle and bone mass through the stress of load-bearing activities. When the (metabolic) stressors applied are easily met and responded to by the (metabolic) reserves in the body, you have a situation where the stress can have a net effect of improved systemic function.
However, stress can also have a dark side. When (metabolic) stressors are applied in excess of the (metabolic) reserves of the body - especially continuing over time - the system will incur a breakdown. It’s a lot like spending more money than you have in the bank: the result is debt. And debt is damaging for the way it impairs our ability to maintain a kind of equilibrium that is conducive to thriving over time. Metabolic debt may result in illness and imbalances of varying degree as the system is unable to afford to continue to repair, adapt, and adjust to ongoing pressures over time. Debt collectors might be seen as the illnesses and imbalances themselves, rearing their ugly heads at last to demand compensation.
An equation for metabolic health: Demand = Reserves
Another way to think about this is the U-shaped curve - which was a principle I discussed in a previous post and can be reviewed there. The center of the U is where physiological health is more optimal for an individual, the left side of the U being where deficiencies are more pronounced and the right side of the U being where excess is more pronounced. Therapeutic or beneficial dosages of a given stressor are denoted by the center of the U. Note that these stressors involve nearly every conceivable type of metabolic pressure including nutrient components, exercise, emotional pressures, drugs, etc though possibly exclude some very extreme cases of substances that are lethal in microscopic dose. The center of the U may vary quite a bit according to biochemical individuality and the larger metabolic context an individual finds him/herself in.
The result of any stress in the body will depend upon where the stressor lands in the U-shaped curve, which is ultimately also a function of what metabolic reserves an individual has to adapt to the pressure(s). Metabolic reserves in part help us situate stressors in the center of the U for our body and we’ll discuss them more a bit later. A summary and recap of the most common stressors we encounter in life include:
exercise/physical exertion
exposures to pathogens or immune antigens, perhaps advancing to infections and allergens, respectively
acute injury
emotional tension/drama/trauma/abuse
dietary intake including specific nutritional balances or imbalances resulting in excess or deficit
medication and supplement dosage and duration
environmental exposures such as chemical pollutants and hazardous chemical exposure
Inflammatory processes of many kinds are impacted by other stressors and can themselves become major metabolic stressors, at times driving a self-perpetuating spiral of dysfunction
Genetic polymorphisms/variations resulting in altered capacities for metabolic action
Choosing the Right Words
As we study complex systems and understand that many seemingly-isolated diagnoses or symptoms are not isolated but in fact connected to larger conversations of systemic (metabolic) dysregulation of varying degree, it becomes more challenging to give succinct or even distinct names to disease states. This is a true challenge of systems medicine (6,7).
One of the biggest challenges we face is how best to talk about the multitude of disease states and imbalances that arise from complex systems and involve multiple players of metabolic dysregulation - which themselves feed back and exacerbate the vicious cycle of breakdown, as systems are wont to do. To the highly observant and curious individual, there will be some predictable patterns and rules emerging in what to others looks only like a chaotic fog of noise requiring spot-treatments. Not only do many otherwise highly trained clinicians fail to see the patterns of breakdown in the bigger metabolic picture, but those who do still currently struggle to build a formal consensus regarding the most concise and accurate language to describe them.
In medicine, we treat based upon diagnosis. Before germ theory, there could be no diagnosis of a staph infection, even in the presence of a staph infection. Before understanding brain imaging and neurochemistry, there could be no diagnosis of epilepsy, even when there was in fact a case of epilepsy. Therefore, treatment in both of these instances and many more, was limited. We have come a long way in being able to see the mechanics of the complex living system, but we have a very long way yet to go. Much diagnostic terminology is itself often overly reductionistic and misleads patients and practitioners in terms of the nature of the big picture. Inadequate diagnostic terminology for systemic dysregulation will limit our ability to understand the important higher order relationships within the body and thus, will impair our ability to treat their imbalances more effectively. What is needed is updated terminology that more often reflects the “big picture” patterns and tendencies for dysregulation as well as appropriately-related treatments applied to the diagnosis of systemic dysregulation.
Okay. Pause and take a deep breath!
Have you managed to absorb everything so far without feeling dizzy and falling out of your chair? While the science of complex systems may seem much more incomprehensible and unwieldy than its reductionist predecessor, the good news is that the emerging systems-based treatment strategies show promise for being far superior in terms of their efficacy, sustainability, and even financial accessibility! We’ll dive into more of these very practical strategies soon (maybe you’re already practicing some!), but for now, let’s summarize what we have understood thus far:
A body is a complex system composed of relationships that cannot be fully understood through reductionist methods of isolating parts
Metabolism is the language of the complex living system that reflects higher order regulation of systemic function
A large percentage of chronic illness and imbalance (arguably all) involves some particular and relatively predictable patterns of metabolic dysregulation that implicate the stress-response system, or neuroendocrine system
Outlining and studying these patterns can help us to better understand disease pathophysiology, develop more appropriate diagnostic terms, and better treat patients who suffer from chronic illness or who simply want to prevent that suffering in their future
·
In Part III, we will look much deeper at the details and patterns present in metabolic dysregulation and decompensation of the stress-response system. We will also learn what this means, in practical terms, for disease prevention and recovery. Practical tips are on the way!
To continue reading, head over to Part III !
References
(4) McEwen BS. Stressed or Stressed Out: what’s the difference? J Psychiatry Neurosci. 2005. 30(5) 315-318
(6) Fink G, Pfaff D, Levine J. Handbook of Neuroendocrinology. Elsevier, 2012
(7) Silverman MN, Herm CM, Nater US. Neuroendocrine and Immune Contributors to Fatigue. PMR. 2010; 2(5) 338-346.
Copyright 2019 Sci Sense Nutrition All Rights Reserved