“Fueling Growth: The Physiological Role of Macronutrients in Muscle and Fat Metabolism”

[7evenvox22]

Spoiler: Macronutrients and Hypertrophy

The main context in which macronutrients matter is for body composition (body fat, water weight, and muscularity), which involves weight training too, as that is a large determining factor of your muscularity. We will dive into how these macronutrients actually affect weight training outcomes, hypertrophy, and weight loss.
The three primary macronutrients—proteins, carbohydrates, and fats—each play very distinct roles, and the degree to which these macronutrients actually help hypertrophy is very situational.

Spoiler: Protein and Hypertrophy

Protein: The Building Block of Muscle​

Mechanisms that benefit hypertrophy:​

• Stimulates myofibrillar protein synthesis (MYOPS) which creates new contractile proteins (which is the only cause of resistance training based muscle growth)
• Stimulates mTOR / muscle protein synthesis (MPS) which repairs muscle damage (but does not build muscle)

When does protein help for hypertrophy?

• Protein only helps within the 48 hour period following a training session. After 48 hours of no training, MYOPS is no longer being stimulated and the high threshold muscle fibers (which are the first to begin atrophying) will now begin to atrophy - regardless of protein intake.
• Protein continues to assist in repairing muscle damage for far longer than a 48 hour period, because muscle damage can be present for many days. This happens through mTOR which can still be stimulated by protein intake.
• So… protein can almost always REPAIR muscle but it cannot always BUILD or MAINTAIN muscle. If you are not actively training, the only time that protein would maintain muscle tissue is if you are atrophying for so long that even your type 1 muscle fibers (the muscle fibers that you stimulate just by walking around, typing on your keyboard, etc) begin to atrophy - in that case, protein could maintain those fibers, because they are still being stimulated by daily activities.

Spoiler: Carbohydrates and Hypertrophy

Carbohydrates: The Primary Energy Source​

Mechanisms that benefit hypertrophy:​

• Increases motor unit recruitment: since type 2 muscle fibers rely on anaerobic glycolysis, they require sufficient glucose in order to be recruited properly. As you learnt earlier, motor unit recruitment is one of the biggest factors for hypertrophy. Without sufficient carbohydrates, your type 2 muscle fibers cannot use any other type of fuel (e.g. fat, ketones, or stored body fat) for efficient energy production.
• Spares protein: when sufficient carbohydrates have been consumed, gluconeogenesis will be reduced, and therefore the amino acids that were obtained from your protein intake will not be wasted and converted into glucose.
• Decreases excitation contraction coupling failure (ECCF): low muscle glycogen, a consequence of a low-carbohydrate diet, can lead to calcium ion-related fatigue, known as ECCF, which reduces mechanical tension (which is one of the other biggest factors for hypertrophy). Eating sufficient carbohydrates decreases ECCF.

When do carbohydrates benefit hypertrophy?

• Carbohydrates only function to improve hypertrophy by improving the stimulus that you can impose on your muscles within a training session, and therefore, their utility is predicated on whether you are planning to train in the near future. For example, if you just trained yesterday but now you are going on a holiday for the next week and will not be training for at least a week, consuming carbohydrates for the next week is useless and will not be benefitting hypertrophy at all, nor will it prevent atrophy.

Spoiler: Fats, Calories and Hypertrophy

3. Fats: The Ultimate Evil​

Mechanisms that benefit hypertrophy:​

NONE except for maybe MARGINAL effects on hormone production, which won’t even be relevant if you are taking exogenous hormones.
“But what about calories? Fats have a lot of calories which could help me get into a caloric surplus if I have trouble eating enough!” Here are some quick pills that you need to swallow:

• 1. Calories are MEANINGLESS for hypertrophy as long as you have sufficient body fat stores. If you are 70kg at 15% body fat, that means you have 10.5kg of body fat. There are roughly 7700 calories in 1kg of body fat, therefore you have an 81,000 calorie surplus already on your body. The only nutritional factors that matter for hypertrophy are eating sufficient protein and eating enough carbs to keep your glycogen stores full. I guarantee you 99.9% of you are not lean enough to be worrying about calories.
• 2. Fat intake is a hard gainer’s worst nightmare. Many “hard gainers” try to consume large amounts of foods like peanut butter, oil, butter, milk, cheese, etc. and these actually hinder their goals of building muscle because these foods contribute nothing towards hypertrophy but they fill up your stomach, satiate you, take a long time to digest, and essentially stop you from having the appetite and digestion space to be consuming foods like carbohydrates and protein that will actually benefit you. Many “hard gainers” will talk about eating 5000 calories and waking up 1kg lighter the next day… and then you realize that it’s because their diets are extremely fatty with not enough carbs, so they’re losing water weight from their glycogen stores depleting while they’re putting fat on at the same time, and so they think they “didn’t eat enough” even though they were in a surplus and are gaining body fat.

I repeat… caloric intake is IRRELEVANT for hypertrophy. There are 3 dietary factors that matter for hypertrophy:

• 1. Sufficient protein to stimulate MYOPS and create new contractile proteins.
• 2. Sufficient carbohydrates to maximize the two most important elements of training stimulus (mechanical tension and motor unit recruitment)
• 3. Sufficient energy, but this includes not only calories but STORED calories. Fat tissue is stored energy that your body can use for later. Why would you eat a bunch of triglycerides when you already have enough stored in your adipose tissue? Lipolysis (breaking down triglycerides into energy) is just as effective as eating a bunch of fat, but it keeps you leaner in the process).

“But when I wasn’t eating enough, I was losing weight and losing strength!”

• Track your carbohydrates and protein at the time. I can almost guarantee that it was your carbohydrate intake that was the main shortcoming. Calories overall are a proxy for carbohydrate intake (since, if you aren’t paying attention to what you eat, you will obviously be eating more carbohydrates on average if you are eating more calories). If you are eating in a calorie deficit (or even at maintenance) while eating a lot of fat though, you are getting very little actual macronutrients that will benefit your workout, and therefore it’s understandable that you will mistake the carbohydrate deficiency as being a calorie deficiency.

Spoiler: Ideal Macro Consumption

So to put it simply, we have learnt that you need protein AFTER training, you need carbohydrates BEFORE training, and you don’t need fat at all. Let’s outline the ideal macronutrient consumption ranges:
Protein: 0.75-1g per lb
Carbohydrates: 2.5-4g per lb
Fats: 0.1g per lb
This means if you’re a 200lb male, you should be eating 150-200g of protein, 500-800g carbohydrates, and 20g fat per day.

Spoiler: Fat Loss: Mechanisms

Hormones:​

• Insulin: A peptide hormone made by pancreatic beta cells, released when blood glucose is high. It binds to cell receptors, activating Glut-4 to uptake glucose. Insulin boosts glycogenesis, lipogenesis, and amino acid uptake while inhibiting gluconeogenesis and lipolysis.
  Glucagon: A peptide hormone from pancreatic alpha cells, opposing insulin. Released during low blood glucose, it triggers glycogenolysis and lipolysis via kinase cascades, increasing blood glucose and free fatty acids.
  Epinephrine: A catecholamine from the adrenal medulla, released during stress. It activates adrenergic receptors, promoting glycogenolysis and lipolysis while blocking glycogenesis, raising blood glucose and fatty acids.
• Cortisol: A stress hormone from the adrenal cortex, regulated by ACTH/CRH. It raises blood sugar by stimulating gluconeogenesis/glycogenolysis while blocking insulin's Glut-4 action (contributing to diabetes risk). Cortisol also breaks down muscle (proteolysis) and fat (lipolysis via HSL), explaining the fat redistribution (midsection/face) in Cushing’s disease.
  Triiodothyronine (T3): Thyroid hormone triggered by TSH/TRH. Binds nuclear receptors to boost metabolism by increasing Na+/K+ ATPase production (raising ATP demand) and enhancing lipolysis.

Macronutrient metabolism:​

• Carbohydrates: Glucose, from digested carbs, fuels ATP production via glycolysis, TCA cycle, and ETC. Simple carbs (mono-/disaccharides) break down easily; complex carbs (oligo-/polysaccharides) take longer. Glucose is stored as glycogen (glycogenesis) or made from non-carbs (gluconeogenesis). It’s broken down for energy via glycolysis (yielding pyruvate) or glycogenolysis (releasing glucose). Without oxygen, glycolysis leads to lactic acid. One glucose molecule can produce 32-34 ATP.
• Lipids: Fatty acids are stored as triglycerides (lipogenesis) or broken down for energy (lipolysis). Hormones regulate both processes. In lipolysis, triglycerides split into fatty acids and glycerol. Fatty acids undergo beta-oxidation, forming acetyl-CoA for the TCA cycle or ketones. A 16-carbon fatty acid yields ~129 ATP.

Spoiler: Fat Loss: Application

Maximizing Fat Loss Mechanisms: Lipolysis and Beta Oxidation​

Fat loss occurs through a series of biochemical processes, primarily lipolysis (the breakdown of stored fat into free fatty acids) and beta-oxidation (the burning of those fatty acids for energy). To maximize fat loss, both processes must be optimized. This article explores how to enhance lipolysis and beta-oxidation naturally and through pharmacological interventions.

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1. Maximizing Lipolysis (Fat Breakdown)​

Lipolysis is the process by which triglycerides in fat cells are broken down into free fatty acids (FFAs) and glycerol, which are then released into the bloodstream to be used as fuel.

Key Factors for Maximizing Lipolysis:​

• Hormonal Activation:
  • Catecholamines (Epinephrine & Norepinephrine) – Bind to beta-adrenergic receptors (especially β1, β2, β3) to stimulate lipolysis.
  • Glucagon – Works alongside catecholamines to enhance fat breakdown.
  • Low Insulin – Insulin inhibits lipolysis, so keeping insulin low (via fasting, low-carb diets, or drugs) promotes fat breakdown.
• Exercise:
  • High-intensity interval training (HIIT) and fasted cardio increase catecholamine release.
  • Cold exposure (e.g., cold showers, ice baths) activates brown fat, increasing lipolysis.

Drugs That Enhance Lipolysis:​

Clenbuterol: β2-agonist → ↑cAMP → ↑lipolysis. Powerful but can cause tachycardia. Yohimbine: α2-antagonist → blocks anti-lipolytic effects. Best in fasted state because insulin inhibits lipolysis.

Ephedrine + Caffeine: Stimulates catecholamines → ↑lipolysis. Synergistic fat loss combo.

Semaglutide (GLP-1 Agonist): Indirectly ↑lipolysis via insulin suppression. Also reduces appetite.

Growth Hormone (GH): Stimulates HSL (hormone-sensitive lipase). Expensive, best used in fasted state (due to insulin once again).

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2. Maximizing Beta-Oxidation (Fat Burning)​

Once FFAs are released, they must be transported into mitochondria and undergo beta-oxidation to be converted into ATP (energy).

Key Factors for Maximizing Beta-Oxidation:​

• Mitochondrial Efficiency:
  • Carnitine – Transports fatty acids into mitochondria.
  • Exercise (especially aerobic) – Increases mitochondrial density.
  • Ketogenic Diet / Fasting – Shifts metabolism to rely on fat oxidation.
• Metabolic Rate:
  • Thyroid Hormone (T3) – Increases metabolic rate and fat oxidation.
  • AMPK Activation (via exercise, fasting, or drugs like metformin) – Promotes fat burning.

Drugs That Enhance Beta-Oxidation:​

L-Carnitine: Facilitates fatty acid transport into mitochondria. Best injected (oral absorption is poor).

Berberine / Metformin: Activates AMPK → ↑fat oxidation. Also improves insulin sensitivity.

T3 (Cytomel): ↑Metabolic rate → ↑fat burning. Risk of muscle loss if overused.

Ketone Esters / Exogenous Ketones: Forces body into ketosis → ↑fat oxidation. Useful for non-keto dieters.

GW501516 (Cardarine): PPARδ agonist → ↑fat oxidation + endurance. Controversial (potential cancer risk). Depletes carnitine—relies on sufficient carnitine for beta oxidation effects.

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Best Stack for Maximum Fat Loss​

For those considering pharmacological aids, a well-structured stack could include:

1. Lipolysis Boosters: Clenbuterol (2 weeks on/off) + Yohimbine (fasted cardio) + GH
2. Beta-Oxidation Enhancers: L-Carnitine (injectable) + Cardarine (PPARδ agonist)
3. Metabolic Support: T3 (low dose) + Berberine (for AMPK)

Note: Always consult a doctor before using any fat-loss drugs, as many have side effects.

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Why do lipolysis and beta oxidation matter? Isn’t it just calories in calories out?​

To maximize fat loss, both lipolysis and beta-oxidation must be optimized. The main missing piece of the puzzle when you think it’s calories in calories out is you’re forgetting about burning glucose/glycogen as fuel. If you have low lipolysis, you will prioritize burning glucose even at rest, which means you will not be able to maintain sufficient glycogen stores (which are mandatory for optimized hypertrophy as we’ve established), and you’ll be burning less fat and more glycogen each day. Cumulatively, over a period of weeks, this will add up to losing out on kilograms of fat loss, and being perpetually glycogen depleted.

Spoiler: Carbohydrate Selection

Carbohydrate Selection for Optimal Energy Partitioning: Why White Sugar is King (For Some)​

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The Problem with Modern Carb Selection:​

Most people blindly follow generic advice like "eat complex carbs" or "avoid sugar" without understanding energy density, digestion speed, and appetite impact. The truth? Carbohydrate selection should be based on your incretin/metabolic profile:

• Low appetite + high BMR? → White sugar is ideal (high caloric density, minimal bulk)
• High appetite + low TDEE? → Fiber-rich carbs (low caloric density, high satiety)

Let’s break it down.

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White Sugar: The Ultimate High-BMR Fuel​

If you struggle to eat enough (hard-gainers, high-metabolism individuals), white sugar is the most efficient carb source available.

Why?

Extreme caloric density – 4 kcal/g (same as all carbs, but with zero water or fiber)
Maximal volumetric efficiency – Dissolves in water completely, density of 1.6g/cm³
Rapid digestion – Efficiently hydrolyzed by sucrase into glucose and fructose, minimal digestive stress.
Pure energy – No micronutrient competition (unlike fruit/honey)

Macros per 100g:

• Calories: 400
• Carbs: 100g (all sucrose)
• Fiber: 0g
• Water: 0g

Compare that to:

• Cooked rice: ~130 kcal/100g (mostly water), 0.7g/cm³
• Oatmeal: ~68 kcal/100g (fiber + water), 1.3g/cm³
• Sweet potato: ~86 kcal/100g (water + fiber), 0.5g/cm³

If you need calories without stomach distension, sugar is unbeatable.

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Who Should Avoid White Sugar?​

If you have:
High appetite (prone to overeating)
Low BMR (easy fat gain)
Poor glucose tolerance (pre-diabetic, insulin resistant)

→ Sugar will make you fat.

For these people, low-calorie, high-satiety carbs are superior:

• Vegetables (broccoli, spinach, zucchini) – ~25 kcal/100g, 0.4g/cm³
• Psyllium husk – ~20 kcal/100g (mostly fiber), 0.6g/cm³
• Konjac noodles – ~10 kcal/100g (pure fiber), 1g/cm³

These foods mechanically fill the stomach without adding significant calories, suppressing appetite through sheer bulk.

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Practical Applications:​

For the Hardgainer (Low Appetite, High BMR):

• Add white sugar to shakes, milk (preferably skim milk because fat is evil), coffee, or meals.
• Use syrups (maple, glucose) for easy liquid calories when applicable
• Avoid fiber-heavy carbs (they’ll fill you up too fast)

For the Fat-Prone (High Appetite, Low BMR):

• Base meals around vegetables, konjac, psyllium
• Never drink calories because they are not satiating (eliminate juice, soda, milk, sugary coffee)
• Use fiber supplements to blunt hunger between meals

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White Sugar's Glycemic Index: The Overblown Myth​

• Glycemic index: 65 (moderate, not extreme)
• Lower than: White bread (75), rice (70), potatoes (78-111)
• Why? 50% fructose (GI 15-19) slows glucose release

Reality:

• Only relevant for insulin-resistant individuals
• Healthy metabolisms handle it fine
• Less crash-prone than pure glucose/dextrose

→ GI is a non-issue for intended users (hardgainers/high-BMR)

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Conclusion:​

Sugar is not evil—it’s a tool.

• Under-eaters? Sugar is the most efficient way to hit calorie/carbohydrate targets without digestive stress.
• Over-eaters? Fiber is your best friend for appetite suppression.

Stop moralizing food. Optimize for your physiology.

Spoiler: GLP-1 Agonists

GLP-1 Agonists for Fat Loss: A Raw Comparison​

Appetite signaling is 90% of the battle with weight loss. If you can’t be bothered eating, you will naturally lose weight. The majority of appetite signaling comes from incretins, which are gut hormones such as GLP-1 and GIP. Weight loss now has little to do with willpower—it's about optimizing your incretins through pharmacology. Semaglutide, tirzepatide, and retatrutide are the three contenders, each with distinct advantages.

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1. Mechanism: Single, Dual, or Triple Hormone Manipulation​

Semaglutide – The original GLP-1 agonist. Works by:

• Slowing gastric emptying
• Suppressing appetite via central nervous system action
• Stimulating insulin secretion
• Simple. Effective. Limited.

Tirzepatide – Dual GLP-1 + GIP agonism. Adds:

• Enhanced insulin sensitivity (GIP effect)
• Potentially greater fat oxidation
• More robust glucose control than semaglutide
• Superior to semaglutide in trials, but still not the final form.

Retatrutide – The first triple agonist (GLP-1 + GIP + glucagon).

• Glucagon increases energy expenditure (burns more fat)
• Early data suggests 24%+ weight loss—unmatched by the others
• Potential for better metabolic flexibility
• The future, if tolerability holds.

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2. Efficacy: Fat Loss & Glucose Control​

Semaglutide (Wegovy/Ozempic)

• Weight loss: ~15% at 68 weeks
• HbA1c reduction: ~1.5–2.0%
• Cardiovascular benefit: Confirmed (SELECT trial)
• Good, but no longer the best.

Tirzepatide (Zepbound/Mounjaro)

• Weight loss: ~21% at 72 weeks
• HbA1c reduction: ~2.0–2.6% (superior to semaglutide)
• Cardiovascular data: Pending (likely positive)
• Currently the most balanced option.

Retatrutide (Phase 2 Data)

• Weight loss: ~24% at 48 weeks
• HbA1c reduction: ~2.0–2.5%
• Too early for CV or long-term data
• If approved, it will redefine the standard.

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3. Side Effects:​

All three cause nausea, vomiting, diarrhea—standard GLP-1 fare.

• Semaglutide: ~20-30% nausea (most tolerable)
• Tirzepatide: ~30-40% nausea (GIP adds GI distress)
• Retatrutide: Likely worse due to glucagon’s metabolic push
• If you can’t handle discomfort, semaglutide is the safest bet.

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4. Cost & Accessibility:​

• Semaglutide:
  • 900–1,300/month
  • Insurance coverage decent for T2D, spotty for obesity
  • Oral version available (Rybelsus)
• Tirzepatide:
  • 1,000–1,500/month
  • Coverage improving, especially for obesity (Zepbound)
• Retatrutide:
  • Expected to be the most expensive ($1,500+?)
  • No guarantee insurers will cover it early on

Semaglutide is the most accessible, tirzepatide is catching up, retatrutide is a luxury. These prices are for mainstream sources. Inquire in the private discord about other sourcing options.

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5. Protocols​

• Semaglutide:
  • Must titrate dose upwards to mitigate side effects
  • Start with 0.25mg administered once weekly
  • Titrate up towards 0.5mg-1mg over the course of 4-8 weeks
• Tirzepatide:
  • Must titrate dose upwards to mitigate side effects
  • Start with 2.5mg administered once weekly
  • Titrate up towards 5mg-10mg over the course of 4-8 weeks
• Retatrutide:
  • Must titrate dose upwards to mitigate side effects
  • Start with 2mg administered once weekly
  • Titrate up towards 4mg-8mg over the course of 4-8 weeks

Semaglutide is the most accessible, tirzepatide is catching up, retatrutide is a luxury. These prices are for mainstream sources. Inquire in the private discord about other sourcing options.

6. Conclusion:​

• All around best option: Tirzepatide (best balance of efficacy and price)
• For those prioritizing safety/tolerability/price: Semaglutide
• For the pharmacologically ambitious: Retatrutide

Spoiler: Trenbolone

Introduction:​

Trenbolone has a reputation for being a magical yet very dangerous compound. It is unfairly fearmongered due to simply being abused by people. As is the case with anything, the dose is the poison. Trenbolone has arguably the most interesting and unique properties of any steroid. Its benefits go far beyond simple androgen receptor agonism.

Androgen Receptor Affinity/Potency:​

Trenbolone agonizes the androgen receptor approximately 4.5 times more potently than testosterone. This means that 450mg of testosterone and 100mg of trenbolone will exert the same AR-related genomic effects on hypertrophy.

Extreme Anti-catabolism:​

Trenbolone is the strongest anti-catabolic steroid in existence, and it has this title due to its several unique pathways of decreasing glucocorticoids.

Decreased tyrosine aminotransferase (TAT) expression:

Tyrosine aminotransferase is a gluconeogenic enzyme (meaning it causes gluconeogenesis, AKA, in this context, the breakdown of amino acids into ATP or glucose). Trenbolone decreases tyrosine aminotransferase expression in the liver, and thus limits the breakdown of tyrosine, limiting catabolism. [1].

Decreased glucocorticoid receptor (GR) expression in muscle tissue:

Glucocorticoids, such as cortisol, have catabolic effects through agonism of glucocorticoid receptors, wherein they cause gluconeogenesis and waste precious amino acids by converting them into immediate energy. Trenbolone drastically decreases the number of GR in skeletal muscle, thus decreasing the number of receptors that these glucocorticoids can bind to. [2].

Increases Satellite Cell Responsiveness To IGF-1:​

Trenbolone potently increases the proliferative responsiveness of skeletal muscle satellite cells to IGF-I. This causes more new muscle tissue to be built for the same IGF-1 concentration. [2]. This also synergizes with the glucocorticoid and TAT effects to drastically improve insulin sensitivity.

What Does This Mean For Nutrition?​

Trenbolone decreases your protein demands by decreasing the rate that amino acids are broken down into glucose. Trenbolone excels in a steep deficit because you can hold onto amino acids and skeletal muscle better even with minimal protein intake.

References:​

[1] https://pubmed.ncbi.nlm.nih.gov/6134779/

[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC8396102/

 

[gigacumster3000]

sigh... another one trying to lookmax with fitness shit

 

[Noesis]