Explore the meaning of anabolism and catabolism in this comprehensive guide to the physiological factors and hormones that impact muscle growth and muscle loss.
- Exactly what the term metabolism really means.
- What the major factors are that impact catabolism and anabolism.
- About the impact of insulin on muscle protein synthesis.
- The role of nourishment upon growth hormone, and insulin and IGF-1 production
- How testosterone plays a significant role in the growth and maintenance of skeletal muscle tissue.
- About the three major estrogens produced in the steroidogenesis pathway of humans: estradiol, estrone and estriol.
- Why thyroid hormones are a major regulator of the human metabolism.
- Why stress hormones are not something that should be avoided/inhibited at all costs.
5g. Thyroid Hormones
5h. Stress Hormones
Two of the most frequently thrown around words in bodybuilding subculture are “anabolic” and “catabolic”. However, I’m guessing that the majority of laypeople don’t actually know much about these terms beyond the fact that the former refers to building and the latter to breaking down.
Given that the main focus of many physique competitors and athletes alike is to improve their body composition, muscular hypertrophy and fat loss are often their primary concerns. Therefore, it seems prudent to cover the basics of what exactly anabolism and catabolism mean in these respects. Moreover, it’s important to understand what these two classes of reactions mean in the grand scheme of things for living organisms.
This guide is intended to cover the major factors of the human endocrine system and their role in protein anabolism and catabolism. Carbohydrate and fatty acid metabolism will be covered in a separate guide, along with the role of anaerobic & aerobic exercise and blood flow.
Metabolism is one of those terms that pretty much everyone knows (and uses) but yet few actually understand, so this section will serve to give you an elementary grasp of what exactly metabolism is.
All living organisms are made up of the simplest living unit—the cell. Yes, this means even simple microbial organisms are “alive”, granted humans are composed of an enormous number (think 100s of trillions) of cells and are highly encephalized while many microbes exist as a single cell (and don’t have brains). But I digress…
Back to the concern at hand, within these cells, chemical reactions are constantly occurring while utilizing and giving off energy in the process. These reactions are divided into two classes that we alluded to in the introduction, those being anabolic and catabolic; the former uses energy to build cell components and molecules while the latter gives off energy as they break down complex substrates.
Therefore, when we speak of metabolism, we are referring to the summation of all of these physiological reactions within the cell that are necessary to sustain life. A multitude of variables such as hormone signaling, physical activity, nutrient availability, and energy status affect how these reactions occur and when they take place. For now, just know that metabolism is a highly intricate system of reactions in cells that sustain life, and there is an inherent energy input & output from these processes (thus the need for nutrients).
The goal of almost any individual in the gym is to improve their body composition (i.e. reduce body-fat levels and/or increase muscle mass). The conundrum is that improving body composition is a give-and-take process. In bodybuilding and the fitness subculture, many people become obsessed with the idea of simultaneously losing fat and building muscle.
However, these events are theoretically mutually exclusive as one scenario requires an energetic deficit and the other requires an energetic surplus. Thus, when I come across a trainer or some magic program that “guarantees” it will help you build muscle and lose fat at the same time, I know to steer clear as that is a pretty arrogant claim unless that individual plans to overcome thermodynamic laws.
So one way to think of improving body composition is like a see-saw between building muscle and losing fat—if you want to increase one then the other will have to decrease.
This is why the traditional approach for many gym-goers looking to improve their body composition is to alternate between periods of building muscle mass and losing fat; colloquially, people usually refer to these timeframes as “bulking” and “cutting”, respectively. The other option is to be in a “maintaining” phase (neither building/losing muscle nor losing/gaining fat).
So let’s take a look at what role protein anabolism and catabolism play when it comes to this predicament of improving one’s body composition.
Skeletal muscle tissue serves as the largest reservoir of amino acids in the human body. Many bodybuilders and health enthusiasts love discussing the topic of protein intake, mainly because proteins provide the “building blocks”/amino acids necessary to synthesize muscle tissue.
However, many people misconstrue the message being sent when someone refers to protein synthesis. Proteins are essential macromolecules that play a myriad of roles in humans; they are not solely relegated to muscle tissue and in fact, are quite ubiquitous throughout many body systems:
- Whole-body protein turnover - this is a measurement of the synthesis and breakdown of protein in all organs, skeletal and non-skeletal
- Skeletal muscle protein turnover - this is a measurement of the synthesis and breakdown throughout skeletal muscle tissue
When it comes to improving body composition, it should intuitively make sense to you that we are trying to build skeletal muscle tissue specifically, since we aren’t after, say, hypertrophy of kidney tissue (well, at least not chronically). This isn’t to say that whole-body protein anabolism is “a bad thing” (since it’s actually a vital part of human existence) but just that exorbitant whole-body protein anabolism over a period of time can actually lead to enlarged organs and subsequent health issues.
Before moving on, hopefully, those of you who get a bit confused with all the technical jargon will benefit from this quick overview of some terms that will be used throughout this guide:
- Muscle protein synthesis - refers to the synthesis of protein in skeletal muscle tissue only
- Muscle protein degradation - refers to breakdown/degradation of skeletal muscle tissue only
- Protein turnover - a measurement that detects that balance between protein synthesis and protein degradation
- Muscle protein anabolism - refers to a state in skeletal muscle tissue where synthesis exceeds degradation, and thus lean tissue is being built.
- Muscle protein catabolism - refers to a state in skeletal muscle tissue where degradation exceeds synthesis, and thus lean tissue is being broken down
- Hypertrophy - the growth of tissue (generally in reference to muscle)
- Atrophy - tissue shrinkage; opposite of hypertrophy
Okay, so now we have arrived at the meat and potatoes of this guide and will get into what factors play a large role in protein anabolism and catabolism, which ultimately have ramifications on body composition. As alluded to earlier, anabolic reactions serve to build cellular components and molecules while catabolic reactions do the opposite. Also, recall that anabolic reactions require energy input and catabolic reactions give off energy. So we will breakdown how protein anabolic and catabolic reactions play a role with regards to building skeletal muscle tissue—one of the most pertinent components to improving body composition.
Here is a preview of the topics to be covered:
- Amino acid pooling, transport, and oxidation
- Insulin-like Growth Factor-1 (IGF-1) and IGF-Binding Protein-3 (IGFBP-3)
- Growth hormone
- Androgenic hormones
- Estrogenic hormones
- Thyroid hormones
- “Stress hormones” - glucocorticoids, glucagon, and catecholamines
As noted earlier, skeletal muscle tissue serves as the largest reservoir of amino acids in the body and makes up the largest mass of protein. There are essentially two amino acid pools we are concerned with here–the circulating pool and intracellular pool.
When the body is in a state of starvation (and other catabolic instances), amino acids are released from muscle tissue into circulation and utilized by other body tissues. On the contrary, when protein anabolism is necessary, amino acids can be actively transported from circulation into the intracellular space of muscle cells and incorporated into proteins (thus synthesizing new protein).
So in addition to the availability of intracellular amino acids, protein synthesis/anabolism is also regulated in part by the transport of amino acids into and out of muscle cells.
In animals (mainly carnivores) amino acids provide a generous amount of energy from the oxidation of amino acids. The oxidation of amino acids to ammonia and their subsequent carbon skeletons occurs when there is excessive protein in the diet or during states of starvation, carbohydrate restriction, and/or diabetes mellitus.
Ammonia is excreted as urea via the kidneys in humans, while the carbon skeletons of amino acids enter the citric acid cycle for the production of energy. Some people claim that the stress placed on the kidneys from high protein intake is a case against traditional “bodybuilding diets”, but even upwards of 2 grams of protein per pound of lean bodyweight appear to be safe for those with healthy renal function (though that is a rather exorbitant intake for most natural trainees).
Insulin is a peptide hormone secreted in the pancreas of humans mainly in response to elevations in blood sugar levels (since it acts as an up-regulator of glucose transport proteins). With the onset of a dramatic increase in type-2 diabetes in the United States, insulin has unfortunately found itself being cast down as the enemy of human physiology as we know it.
However, I can assure you that if your goal is to build a lean, muscular physique, then you’ll be well served to let insulin work its anabolic mojo rather than trying to avoid it all costs like so many anti-carb advocates suggest.
Insulin is one of the most potent anabolic hormones in the human body and acts to induce protein anabolism in the entire body when amino acids are replenished. The key here is that a state of hyperinsulinemia (elevated insulin levels) without concomitant availability of amino acids doesn’t appear to increase whole-body protein synthesis (though it does reduce the rate of whole-body protein breakdown).1, 2, 3
Moreover, while insulin does reduce whole-body protein breakdown, it does not modulate the ubiquitin system that is responsible for the regulation of muscle protein breakdown. Therefore, insulin is not a specific reducer of muscle protein breakdown.4
Research suggests that insulin doesn’t directly alter the rate of transmembrane transport of (most) amino acids but it rather increases muscle protein synthesis by drawing on the active intracellular pool of amino acids.5 The exceptions to this are amino acids that use sodium-potassium pumps (mainly alanine, leucine, and lysine) as insulin causes skeletal muscle cells to be hyperpolarized by activation of those pumps.2
This suggests that a state of hyperinsulinemia paralleled with a state of hyperaminoacidemia (elevated plasma amino acid levels) should be quite conducive to facilitating muscle protein synthesis. This is in fact why patients in a state of critical cachexia are often set up with an infusion of amino acids and insulin.
All the scientific mumbo jumbo can sometimes cause us to lose sight of the bigger picture. The take-home message is that insulin is indeed a highly anabolic hormone that is conducive to skeletal muscle protein synthesis but that an exogenous source of amino acids is necessary to create this effect.
As noted above, a state of hyperinsulinemia and hyperaminoacidemia will facilitate muscle protein synthesis, and what better way to induce such a state than by simply ingesting protein and carbohydrates.
However, be careful not to misconstrue the message here to mean “the more insulin the better” as this doesn’t appear to be the case in physiological ranges. Research seems to indicate that while some insulin does amplify the muscle protein synthesis response to feeding, there is a point of saturation in which extra insulin doesn’t confer a more intense response.6
Many people believe that a superfluous rush of fast-acting carbohydrates along with whey protein is ideal, especially after weight training to maximize the muscle protein synthetic response. The reality is you don’t have to “spike” your insulin; a slow, transient insulin response (as seen with low glycemic load carbohydrates) will provide much the same muscle protein synthesis benefits as a rapid, acute surge.
As you may have likely derived from the nomenclature, IGF-1 is a peptide hormone quite similar in molecular structure to insulin and has implications on the growth of humans. IGF-1 is produced mainly in the liver upon binding of growth hormone (GH) and acts either locally on select tissues (paracrine) or systemically (endocrine); thus, IGF-1 is a mediator of the effects of GH. IGF-1 is a potent initiator of the AKT signaling pathway in cells, which has ramifications on cell growth and proliferation.
For practicality purposes, it is important to consider the actions of IGFBP-3 since nearly all IGF-1 is bound to one of 6 protein complexes and IGFBP-3 makes up about 80% of all this binding.
It is suggested that IGF-1 has effects similar to insulin (at high concentrations) on protein metabolism due to its ability to bind and activate the insulin receptor, albeit at a much less potent rate (about 1/10th the potency of insulin).7
Therefore, it’s not surprising that IGF-1 administration promotes protein anabolism in skeletal muscle and the whole body.8, 9 A unique characteristic of IGFBP-3 is that it appears to inhibit skeletal muscle atrophy (i.e. it’s anti-catabolic).10
Given that IGF-1/IGFBP-3 is beneficial with respect to stimulating protein anabolism and preserving skeletal muscle tissue in times of muscle wasting/cachexia, the most prudent question most people are probably wondering about is, “How do we increase circulating levels of these moieties?”
Well, several factors influence the amount of IGF-1/IGFBP-3 (and GH) present in the blood at any given moment, including, but not limited to: genetics, biorhythms, age, exercise, nutrient status, stress, disease state, and ethnicity.
However, many people may assume that an increase in insulin will confer a subsequent elevation in IGF-1, which is not the case (remember, insulin and IGF-1 are structurally and somewhat mechanistically similar, but they’re produced in different fashions). Intuitively, since GH is ultimately what leads to the production of IGF-1 (roughly 6-8 hours post GH release/administration), it makes the most sense to focus on elevating endogenous GH levels (which we will discuss in the growth hormone section of this guide).
Editor's Note on Deer Antler Velvet supplements that claim to increase IGF-1: In recent years some supplement companies have tried to make the claim that deer antler velvet extracts are conducive to skeletal muscle growth and healing in humans due to the potent amount of IGF-1 contained in said extracts. However, don’t fall prey to the hype behind these supplements as IGF-1 is a peptide hormone, therefore any oral form of it will be rapidly cleaved in the gastrointestinal (GI) tract before it gets into circulation. This is why people who are type-1 diabetics have to inject insulin (also a peptide hormone) and can’t just take an oral form of it since that too would be degraded by the GI tract.