Anabolic resistance

Here is a brief summary

1. Anabolic resistance is the impaired ability to build muscle caused by excessive calorie intake over time.
2. To build muscle it is necessary that you eat more calories, but there is a point of diminishing returns. You may reach a "nutrient overload" where fatty acids, triglycerides and glucose become toxic.
3. Insulin resistance is the first step towards anabolic resistance. You don't have to be fat to develop insulin resistance. Anyone who consistently overeats can develop insulin resistance within a few weeks.
4. To get anabolic resistance under control, you need to reduce your calorie intake below maintenance calories for a few weeks. Try to prevent inflammation as much as possible.

When mass gain goes down the drain

You have been dieting hard for months and have become hard and defined. Even though you have achieved a great shape, you have lost some muscle mass. Now the diet is over and you feel like eating a lot more again. This year, you tell yourself, you want to be bulkier than ever before.

You start to eat a lot to build up mass. You eat extra calories and train like a beast. Over the next few weeks, everything goes well: your strength increases, you get an incredible pump during training and you are hungry all the time. This is what "anabolic" feels like. You know you're growing.

After a while, however, things start to change. You start to look softer as your body begins to build fat. That full and muscular look you started with begins to fade. You become softer and flabbier, your abs start to diminish, and sight gags start to look at you in love.

Fast forward - a few months later. Your strength gains are less impressive, that legendary pump is gone and your joints start to ache - a sign of underlying chronic inflammation.

What went wrong? The simple answer is that the fat build-up generated by your mass-building phase has created a state of anabolic resistance. Yes, you need a calorie surplus to build new muscle, but a calorie surplus is only helpful up to a certain point. If you go beyond that point, then excessive fat gain, triglycerides and glucose become toxic.

At this point you are in a state of "nutrient overload" and you have reached the point of diminishing returns. Many exercisers have experienced this during their bulking phase.

When taken to the extreme, the same changes that limited your muscle growth during periods of nutrient overload will also cause metabolic syndrome, diabetes and cardiovascular disease.

This is not to say that you run the risk of becoming chronically obese and developing diabetes during your next mass-building phase. Those who train hard are metabolically resilient enough to avoid developing diabetes when calorie intake increases over a prolonged period.

But prolonged nutrient overload will eventually cause negative metabolic adaptations that will lead to some degree of anabolic resistance.

3 steps to anabolic resistance

It's important to understand the reason why your muscle growth slows down while your body fat percentage increases beyond your optimal range. Nutrient overload causes a cascade of negative effects that will eventually throw a spanner in the works of the muscle building process.

This is called anabolic resistance, which stands for a reduced ability to increase muscle protein synthesis in response to amino acids, mechanical overload or other anabolic agents such as insulin or IGF-1.

Excess fat accumulation can make you more resistant to muscle growth even in the presence of normal anabolic hormone levels. This is true regardless of the availability of insulin, IGF-1 or growth hormones.

Although training plateaus are unavoidable, "metabolic plateaus caused by a misguided diet while trying to build additional muscle mass can be completely avoided through smart nutrition. There are three factors associated with nutrient overload that lead to anabolic resistance.

1 - Insulin resistance

Insulin resistance might be the most important factor, as it tends to come about early on.

You don't have to be fat for several years to develop insulin resistance. Take a relatively young, healthy person, put them in a state of nutritional overload and insulin resistance will develop after just a few weeks.

Insulin resistance increases the tendency to store carbohydrates in the form of fat instead of storing them in muscle tissue in the form of glycogen. It also causes the accumulation of triglycerides (fats) in muscle tissue, which contributes to muscle insulin resistance.

When muscle insulin sensitivity decreases, glucose uptake into the muscles also decreases. The result is less stored glycogen, reduced muscle fullness and a reduced pump during training.

A mass-building phase will therefore only work well until you start to become less sensitive to insulin. As your body fat percentage increases beyond the optimal range, your insulin resistance becomes more and more severe.

At this point, things quickly start to go south from a metabolic perspective. Fat stores increase, your training gains slow down and it becomes difficult, if not impossible, to get a pump during training.

2 - Leptin resistance

You have now reached the point of diminishing returns. As your insulin resistance decreases, you build up more and more fat. This is the point where leptin resistance comes into play.

Leptin is a peptide hormone produced by fat cells (adipocytes) that acts as a sort of regulator of metabolism and hunger. Technically, it links changes in your body fat stores to CNS control of energy homeostasis.

It helps to think of leptin as a kind of fuel gauge that measures body-wide energy availability. Leptin monitors body-wide energy stores to coordinate energy expenditure, fat oxidation and overall metabolism.

When fat stores increase, adipocytes release more leptin, which crosses the blood-brain barrier and communicates with leptin receptors in the hypothalamus.

This is a signal that your energy stores are maximally full, which stimulates the hypothalamus to signal the brain and the rest of the body to decrease appetite and increase metabolic rate.

When calorie intake decreases, fat cells produce less leptin. This signals the hypothalamus that energy reserves are low, resulting in increased appetite and lower calorie consumption. However, the effects of leptin are not limited to the hypothalamus.

Leptin receptors are located throughout the body, allowing leptin to coordinate appetite, metabolism and energy expenditure throughout the body.

When fat stores increase significantly, more and more leptin is produced and released into the bloodstream. If leptin levels are high enough over a long enough period of time, you will eventually develop insulin resistance. Leptin binds to the leptin receptors, but it no longer transmits messages.

The level indicator for body-wide energy stores is out of action and any fat-burning effects are lost. Despite the extra body fat, the brain never gets the message that the body's energy stores are full. As a result, some appetite control is lost.

Certain people are more susceptible to this. The lucky ones among us develop only a slightly weaker insulin resistance in response to prolonged periods of bulking and only possibly a certain degree of leptin resistance.

Those of us with a far less resistant metabolism and a pre-existing tendency to build up fat easily will have a much harder time - appetite control is out of action, leading to a continual build-up of fat.

This causes a vicious cycle of increasing leptin resistance, which brings us to the final stage where the shit hits the fan and you develop full-blown anabolic resistance.

3 - ER Stress - The real cause of anabolic resistance

ER stands for endoplasmic reticulum. You can think of the ER as a kind of protein factory.

The endoplasmic reticulum processes metabolic signals to control glucose, lipid and protein metabolism. It is also a primary site of protein synthesis. After being folded and processed in the ER, proteins are transported to the Golgi apparatus for further sorting, "packaging" and distribution.

If the endoplasmic reticulum is the protein factory of your cells, then the Golgi apparatus is Fed-Ex. Proteins are then transported from there to the different parts of the cell.

Together, the endoplasmic reticulum and Golgi apparatus are responsible for the processing, transportation and delivery of all new proteins. The endoplasmic reticulum becomes stressed when the demands on protein synthesis exceed a cell's ability to synthesize, process and transport new proteins to their cellular destinations.

ER stress in adipose tissue

Fat cells are not only passive storage containers for body fat. They also function as endocrine organs that secrete a number of different proteins to control metabolism. These hormones include leptin, adiponectin and other peptide hormones. The larger the fat cells become, the more leptin they secrete, making the endoplasmic reticulum very important for the fat cells.

It is the job of the endoplasmic reticulum/Golgi apparatus to produce and process all this leptin. The system becomes overloaded when proteins are produced faster than they can be processed, resulting in ER stress.

This triggers the so-called unfolded protein response (UPR for short), which reduces protein synthesis and increases ER protein folding capacity to reduce the amount of unprocessed protein that has accumulated.

The problem, however, is that this comes at a price. URP triggers an inflammatory response that can lead to a vicious cycle of inflammation and oxidative stress.

This "metabolic inflammation" is both a cause and an effect of ER stress. Nutrient overload causes an increased need for protein synthesis in fat cells - both for the production of peptide hormones such as leptin, and for the proteins needed for triglyceride production and fat storage.

When nutrient overload ramps up protein synthesis beyond the endoplasmic reticulum's ability to process/fold these proteins, the UPR is triggered. All this protein synthesis is an energy expensive process.

Insulin resistant fat cells cannot take up enough glucose to meet the energy demands of protein synthesis. This triggers further ER stress. The result is a vicious cycle of inflammation, oxidative stress, insulin resistance and leptin resistance.

ER stress in muscle tissue

When nutrient overload triggers an ER stress response in fat cells, the uptake of fatty acids slows down. This causes a shift of these fatty acids into muscle tissue.

Insulin-resistant muscle tissue has difficulty burning this fat for energy, which is why it is stored in the form of intramuscular triglycerides. This ectopic fat storage reduces insulin sensitivity in muscle tissue and causes ER stress in the muscles, which is the root cause of anabolic resistance.

When the ER stress response is triggered in muscle tissue, you are in a state of anabolic resistance. The muscles become less receptive to triggers of protein synthesis. Leucine uptake, mechanical load and even anabolic hormones become less effective at activating the protein synthesis machinery.

In short, nutrient overload is a cause of anabolic resistance. The fatter you get, the more insulin resistant you become. Insulin resistance is both a cause and a consequence of leptin resistance, as it causes fat gain. If you are in an insulin and leptin resistant state, then you are more susceptible to ER stress, which is the primary cause of anabolic resistance.

Two tips to avoid anabolic resistance

1 - Don't get too fat

Keep your body fat within a certain range at all times. The ideal range is different for different people and depends on insulin sensitivity and individual factors. If you exceed this range, you will notice it.

More of the weight you gain will be fat and your gains will slow down, the pump during training will diminish and you won't have the muscle fullness you used to have. It's obviously best to prevent this from happening in the first place by eating smart.

2 - Solve the problem

To get better, we need to push the boundaries, which is why it's not uncommon to find yourself in a situation where you've overdone it on the calories for too long and have reached the point of diminishing returns. But all is not lost.

The only way to move forward in this situation is to go backwards a little. Reduce your calories below your maintenance calorie intake for a few weeks and reduce your carbohydrate intake. Add some cardio if necessary.

If chronic, underlying inflammation induced by nutrient overload could be a real problem, then supplements such as cyanidin 3-glucoside, curcumin and fish oil are available to help limit inflammation and boost your insulin sensitivity.

Increasing your intake of food-based antioxidants or supplements such as superfoods, which are packed with potent natural antioxidants, can also help reduce oxidative stress induced by nutrient overload.

Continue this diet phase to control inflammation and oxidative stress until your body fat is back in an acceptable range.

You will then have eliminated any anabolic resistance and will be metabolically prepared to continue building quality muscle. It's no coincidence that those who alternate periods of increased calorie intake with periods of dieting have bodies that seem to continue to develop over time. Whereas the typical "permabulker" who performs a year-round bulking phase is busily developing a spare tire around the waist.

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From Bill Willis