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Understanding mTOR: a master regulator of hypertrophy and performance

Muscle growth isn’t just about lifting heavy weights and eating enough protein and carbs, it’s about activating the right pathways inside your body. One of the most powerful regulators of muscle hypertrophy and performance is mTOR (mechanistic or mammalian target of rapamycin). This cellular signaling pathway controls aspects such as protein synthesis, cell growth, and energy balance, making it a key factor for bodybuilding and athletic performance. But how does mTOR work, and better yet how can you make it for you for maximum muscle gains?

In short, mTOR is an evolutionarily conserved serine/threonine protein kinase that acts as the central switch for anabolic processes in the body, playing vital roles in muscle and energy synthesis. It exists in two complexes, C1 and C2:

mTORC1

Regulates the rate between protein synthesis and degradation, the size and growth of muscle fibers, and recovery;

mTORC2

Involved in cell survival and cytoskeletal organization but less relevant for hypertrophy.

When activated, mTORC1 increases muscle protein synthesis, allowing muscles to grow larger and stronger in response to training and nutrition.

mTOR activation

There are several ways to induce mTOR activation for muscle growth and performance, and I bet you’re doing at least some of them already:

Resistance training

Mechanical tension (lifting heavy weights) is one of the strongest activators of mTOR;
Eccentric contractions (slow negatives) with a deep stretch stimulate greater mTOR activity;
High volume training may increase muscle fiber stimuli, which triggers repair through mTOR signaling.

Protein and amino acids (particularly leucine)

Leucine, a branched-chain amino acid (BCAA), is a direct activator of mTOR;
Consuming at least 3-5g of leucine per meal can maximize mTOR stimulation;
Whey protein, eggs, and red meat are rich sources of leucine and other essential amino acids.

Carbohydrates and insulin

Carbohydrates spike insulin, which enhances mTOR activation and muscle glycogen replenishment;
Consuming protein and carbs together post-workout creates the ideal environment for muscle anabolism.

Hormonal optimization

Testosterone and growth hormone indirectly support mTOR activation by increasing protein synthesis;
IGF-1 (Insulin-like Growth Factor-1) is a potent mTOR stimulator, increasing muscle repair and growth;
Avoiding excessive cortisol (chronic stress) prevents mTOR inhibition and muscle breakdown.

Nutrient timing and fasting

Post-workout nutrition is critical: fasting too long after training can limit mTOR activation;
Intermittent fasting has a dual effect: prolonged fasting downregulates mTOR, but refeeding with protein and carbs causes a strong anabolic rebound.

Drawbacks

However, as with most things in the human body, constantly activating mTOR pathways comes at a cost. While it’s is essential for muscle growth, chronically high mTOR activation may have drawbacks:

Accelerated aging and disease risk: mTOR activity is linked to aging and maybe certain diseases like acne, cancer, obesity, diabetes, and neurological conditions;
Reduced autophagy: constant mTOR stimulation can inhibit natural cellular repair and metabolic waste management mechanisms;
Balancing mTOR activation with periods of lower activity (for example fasting and low-calorie phases) may improve longevity and metabolic health.

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In conclusion, mTOR is one of the key drivers of muscle growth and performance, and it should be a crucial point for bodybuilders and athletes looking to maximize it. By optimizing training, nutrition, and recovery, you can activate mTOR more frequently for faster gains, better recovery, and increased strength. However, balancing mTOR activity with proper recovery and metabolic health is essential for long-term success, as well as making you look younger for longer. In the end, it’s all about training hard, eating smart and making mTOR work for you.

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Testosterone Replacement Therapy – Is it time for it?

Typically starting at about the age of 30, a man’s testosterone levels drop by about 10% every decade. Together with that, sex binding hormone globulin (SHBG) levels start to increase, “trapping” much of the circulating testosterone and making it effectively unavailable to exert its expected effects on the body. The resulting difference between the total testosterone and the bound, unavailable is what we call free or “bioavailable” testosterone and, more importantly than the total levels of the hormone, plays a major role in the health, drive, quality of life and performance of an individual.

Every man will experience a decline in free testosterone as age comes, but some men will experience it harder and faster than others. The reason for that may be physical, psychological, environmental or as a result of years of natural-production suppression due to steroid usage when younger. When this happens, these men will go through a variety of negative symptoms that can severely impact their day-to-day life and even expose their health to the long-term risks of low testosterone. Some of these risks are:

- Cardiovascular disease
- Cancer
- Diabetes
- Osteoporosis
- Depression
- Alzheimer’s
- Erectile Dysfunction
- Metabolic Syndrome

The last one, metabolic syndrome, may very well be the most common one, and is linked to an insulin-sensitivity condition, believed to be related to type 2 diabetes. It can be defined as the presence of 3 out of 5 of the following risk factors:

1 - Abdominal fat: waist circumference above 40 inches in men; 35 inches in women.
2 - Elevated blood pressure: greater than 140/90 mmHg.
3 - Decreased HDL “good” cholesterol: less than 45 mg/dL in men; less than 50 mg/dL in women.
4 - Elevated triglycerides: greater than 150 mg/dL.
5 - Elevated fasting glucose: greater than 110 mg/dL.

Ok, so at this point we’ve established some of the major risks of low testosterone levels in aging men, but how can you tell if you’re suffering from low testosterone levels? This is usually done via bloodwork, but as the hormone levels naturally fluctuate significantly throughout the day or the week (i.e., if you have been eating and sleeping properly, if your week has been especially stressful or busy), usually at least a few test results under different conditions are required for accurate diagnosis. If one’s testosterone levels are often beneath the physiological levels (male: 300 to 1,000 nanograms per deciliter (ng/dL) or 10 to 35 nanomoles per liter (nmol/L) or female: 15 to 70 ng/dL or 0.5 to 2.4 nmol/L), then that person is a candidate for testosterone replacement therapy. Other than that, while the range is extensive, an individual with low testosterone will experience one or more of the following clinical symptoms:

- Frequent emotional changes
- Diminished sex drive
- Some form of erectile dysfunction (or less rigid erections)
- Decreased morning erections
- Decreased strength and/or muscle mass
- Decreased feeling of well-being
- Reduced mental quickness and sharpness
- Decreased energy, strength and endurance
- Less desire for activity and exercise
- Increased body fat
- Night sweats and trouble sleeping
- Some level of depression and irritability
- Loss of enthusiasm for daily life

Say you’ve established you need to undergo a TRT program, how do you do it? The best way is of course going to a specialized doctor and following his directions. If you want to do it by yourself, though, a good starting point is trying to replace the 5-7mg/day of testosterone that a healthy adult male typically produces with testosterone injections. To save you the math, accounting for the ester availability, that will be around 100mg of injectable testosterone every 10 days (50 mg of testosterone cypionate or enanthate every 5 days would be better to mitigate ups and downs in seric levels). This will probably be enough to keep you in the physiological levels of testosterone action, but further bloodwork is advised to make sure. More than that and you’re no longer in TRT range, but rather doing a steroid cycle.

Other options include the use of transdermal gels and creams, patches, pellets and implants. To stay within physiological testosterone levels range, you will need to check the concentration and bioavailability of the chosen method in order to work out your dose.

However, it may not be that simple. Some individuals may need to use other medications during their TRT programs. These include:

Aromatase inhibitors (Anastrozole/Exemestane): AI’s block the conversion of testosterone into estrogen. TRT patients who suffer estrogen elevations above the top of normal range are often given an aromatase inhibitor.
Selective Estrogen Receptor Modulators (SERMs), (Nolvadex/Tamoxifen): SERMs hinder the action but not the production of estrogen. In TRT contexts, this drug is usually taken to counter the physical manifestations of estrogen-related problems like gynecomastia.
Human Chorionic Gonadotropin (hCG): even at TRT does, Testosterone supplementation suppresses natural production. Over time, this can lead to testicular atrophy. hCG helps restore and maintain Testosterone production and testicular size by mimicking LH and stimulating the production and release of natural Testosterone.
5-Alpha Reductase Inhibitors (Finasteride, Dutasteride/ Propecia, Proscar): These drugs are specific inhibitors of the 5a-reductase, the enzyme responsible for conversion of testosterone to dihydrotestosterone (DHT). In men, DHT has its own pros and cons. DHT is three times more potent than Testosterone, doesn’t aromatize to estrogen, and is associated with high libido. However, it’s also linked to male pattern baldness, acne, and prostate cancer.

As you can imagine, it gets a lot more complex when you add these other drugs to the mix. If you’re going down that route, I strongly advise you to seek professional help.

Overall, the health benefits to be gained overwhelmingly seem to support Testosterone replacement when you consider the beneficial effects to energy levels, metabolism, muscle mass/functionality, and even blood chemistry and cardiac health, if done correctly.

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Crashed Gear – Why it happens and what to do

For those unfamiliar with the subject, let’s start from the beginning: what is crashed gear? It’s simply the term used for when the hormone becomes unsolubilized within the solution and they become separated, usually forming crystals and giving the vial a waxy, sometimes white, sometimes gluey-looking appearance.

So, let’s go over some of the reasons as to why gear crashing may happen:

1 - How long the ester is: Shorter esters (e.g., propionate, acetate or phenylpropionate) form harder, stronger crystals, with a melting point close to 100ºC, while longer esters often have a melting point closer to a human’s body temperature of around 30 to 40ºC, the exception being cypionate, a longer ester with higher melting point. This explains why shorter esters tend to separate from the mixture as the ambient temperature decreases.

2 - Concentration of hormone: As logical as it may sound, the higher the concentration, the higher the tendency to crash. Manufacturers will of course try to compensate for it by using stronger, more concentrated solvents, but there’s only so much that can be done while keeping the gear usable. So, lower-concentrated vials with no blends (just one hormone) will probably crash far less often than the high concentrated stuff.

3 - Solvents used: Some solvents are capable of keeping a mixture stable through lower temperatures more easily than others. Of course, these tend to be more expensive and aren’t used as much.

4 - Mechanical Agitation: If you keep your gear sitting in a shelf or your bathroom closet for too long, crystals may start to form at the bottom, once a single crystal forms, it becomes easier and faster for many more to appear.

5 - Storage temperature: As we’ve discussed later, temperature plays a major rule in the solubility of hormones in oil, with higher temperatures making the gear harder to crash.

6 - Impurities: Any impurities that get pushed into the vial may contribute to forming a crystal. If your gear is on the verge of crashing and an impurity is pushed inside (via a dirty needle or rubber cap, for example), it may become easier for it to reach that crashed state.

So, it’s obvious gear crashing becomes more common comes wintertime, as temperatures decrease drastically, especially in environments with no consistent heating. Now some individuals will panic and toss away their gear as soon as they see it looking weird or crashed. Some will even bad-mouth brands about this online. This is not needed, as crashed gear may come back to its original state following a few basic steps:

1 - Keeping your gear at a proper temperature: Anywhere between 20ºC±10ºC (or 50 to 86 ºF) will probably be fine if your gear is properly made and has not crashed yet.

2 - Heating it up: You can try leaving your vials under hot running water from a tap for a few minutes, if that doesn’t solve it, you can bring water to a boil in a pan and place your vials in there, making sure to keep the water level just below the rubber caps (as some water may get in the vial that way).

3 - Adding more solvent: If you really don’t want to toss away your gear and none of the previous steps solves the issue, you can try ordering solvent online and a microfilter for syringes/needles and add a little bit of solvent at a time (about 1% of the mixture) and heat it up mixing thoroughly. Now please if you want to try this do your research first, know what kind of solvent is used in your particular gear and order the same and keep in mind that the concentration of gear will change slightly. Modifying the concentration of solvent also has to do with post injection pain, learn more by reading the PIP article.

4 - Lower concentration by adding sterile oil: You can simply purchase some sterile oil and add a percentage to your gear. Obviously, you need to do a little math to find out final concentration. It’s also a good idea to add around 1% of total volume of benzyl alcohol to keep your concoction sterile (total concentration of benzyl alcohol is normally over 0.9% to be effective). After doing this, a bit of heat should bring everything back into solution.

While some people will think crashed gear is garbage and got scammed by the store, it shows that there’s actually real hormones in it, otherwise there would be nothing to crash out of the mixture.

test-3-850x560.jpg


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