[@RenaissancePeriodization] Cardio & Weightlifting Now In A Shot IS REAL

Link: https://youtu.be/xXuHFDnZVhA

Short Summary

This YouTube video discusses a promising class of drugs called actin antagonists (like beagrammab) that block actin, leading to muscle growth and fat loss without diet or exercise. Clinical trials have shown significant fat mass reduction (around 20%) and lean muscle gain (3-4%) with minimal side effects, and future research is exploring combinations with existing weight loss drugs for enhanced results, as well as easier administration via pills or patches.

Key Quotes

Here are four quotes from the video transcript that I found particularly insightful or noteworthy:

1. "You take one drug, you lose 20% of your fat mass and gain 3 to 4% muscle mass from one drug with no diet and training in the mix. That's totally insane."
2. "Here's another crazy thing. this act R2 pathway uh is upstream of insulin and leptin and thus you get fat oxidation, you get fat burning without the hunger rebound or the energy decline seen in pure caloric restriction. Kind of your body's just none the wiser for it and it's like wow muscles sure are working hard and it doesn't make any other adjustments seemingly."
3. "Adding drugs will take your physique to places safely that diet and training alone never could. And if you want to go to those places, I think that's well, I think it sounds really exciting."
4. "It's not diet and training versus drugs. It's everything that can help you in a safe long term."

Detailed Summary

Okay, here is a detailed summary of the YouTube video transcript, broken down into bullet points covering key topics, arguments, and information:

I. Introduction: The Promise of Actin Antagonists

• The video introduces the concept of actin antagonists, a drug class that aims to promote muscle growth and fat loss.
• Dr. Mike states the dramatic claim that you can lose 20% of fat mass and gain 3-4% muscle mass with no diet or training.
• He highlights that the health changes are even more significant than just weight loss.
• He questions if it is possible to have cardio and lifting from a syringe.

II. Understanding Actin and the ACTR2 Receptor

• Actin antagonists are engineered antibodies designed to bind to actin molecules.
• Actin normally binds to the ACTR2 receptor, limiting muscle growth.
• Actin antagonists prevent actin from reaching the ACTR2 receptor, removing this muscle growth limitation.
• Normally, the body limits muscle growth to conserve calories for essential functions.
• Constant muscle growth consumes a lot of calories (ATP) to power muscle growth.

III. Clinical Evidence: Begrammab and Increased Energy Expenditure

• Clinical infusions of begrammab (an actin antagonist prototype) increased daily energy expenditure by 200 calories in obese individuals without changes in diet or exercise.
• This is attributed to the energy cost of the ongoing muscle growth.

IV. Fat Oxidation and Visceral Fat Loss

• Actin signaling impacts insulin and leptin and fat burning.
• Begrammab increases fat oxidation (fat burning) without the typical hunger rebound or energy decline associated with caloric restriction.
• The fat burned is preferentially visceral intra-abdominal fat (the dangerous kind) and deeper subcutaneous fat.

V. Brown Fat Activation

• Actin signaling typically limits brown fat activity.
• Actin antagonists convert more fat cells to brown fat-like behavior, increasing fat burning.

VI. Direct Trial Results: Lean Mass Gain and Fat Mass Loss

• Direct trials show lean mass gains of 3-4% and fat mass loss of over 20% in about a year with the drug alone.
• The video emphasizes that these results are achieved without diet or training.
• GLP-1 drugs cannot accomplish this by themselves.

VII. Potential Benefits for Athletes

• Actin antagonists could help athletes maintain muscle mass during injury recovery or time off.

VIII. Potential Side Effects and Management

• Generally well-tolerated, but administered via subcutaneous or IV injection.
• Mild flu-like symptoms and site aches may occur.
• Rare cases of transient elevations in hemoglobin/hematocrit (red blood cells). Phlebotomy might be needed for some patients.
• Rare low-grade nosebleeds or development of red capillaries near the skin (cosmetic).
• Rare instances of elevated liver enzymes.
• Side effect management strategies include rotating injection sites, regular blood work (red blood cells, liver panels), and stopping the drug if needed. Laser therapy for capillaries.

IX. Advantages Compared to Other Weight Loss Drugs

• No reports of hypoglycemia.
• No GI distress, unlike many modern weight loss drugs (semaglutide, tirzepatide).
• Does not affect appetite.

X. Combining with Diet and Exercise

• Suggests use with 500 calorie deficit, diet, and resistance training.
• In clinical tests, the average person lost 4 inches off their waistline and had a 20% reduction of their fat mass with 400mg administered IV every 4 weeks for 24-48 weeks.
• Average people gained 3-4 pounds of muscle during the first 3 months while eating at a submaintenance diet and not lifting weights.
• In combination with diet and exercise, could potentially increase fat loss by an extra pound per week and build several pounds of muscle over 12 weeks.

XI. Combination Therapies: Begrammab and Tirzepatide/Semaglutide

• The video discusses combining actin antagonists with drugs like tirzepatide (Mounjaro) or semaglutide (Ozempic/Wegovy).
• Combination therapies are in phase three clinical trials (BELIEVE and COURAGE trials).
• Begrammab with semaglutide led to 22% fat loss versus 16% with semaglutide alone.
• 90% of the weight loss was pure fat. Begrammab reduces muscle loss from Ozempic by 70%.
• Combination therapy also improved anti-diabetic outcomes.
• FDA filing could happen as early as 2027.

XII. Future Developments

• Next-generation subcutaneous versions are in development (self-injection at home every 6-8 weeks).
• Oral small molecule ACTR2 blockers are in pre-clinical trials (pills, potentially available around 2030).
• Muscle protein sensor patch is being developed to adjust the amount of the drug secreted to maintain muscle mass.
• Genetic alterations for myostatin and actin are in the works (potentially available in the late 2020s/early 2030s) for increased muscle growth response to stimuli.

XIII. Ethical Considerations and Conclusion

• Emphasizes that diet and training are still the foundation. Drugs are an enhancement.
• Using drugs responsibly will become more common as they become safer and more powerful.
• RP Strength will continue to provide updates on pharmaceutical developments.
• Encourages viewers to share their thoughts in the comments.