#291 ‒ The role of testosterone in males and females, performance-enhancing drugs, sustainable fat loss, supplements, and more | Derek, More Plates More Dates Pt.2
Peter Attia and Derek from More Plates More Dates discuss exogenous molecules like testosterone, DHT, DHEA, and progesterone, their impact on male and female health, and the complexities of TRT. They also cover recent FDA peptide updates, myostatin inhibition, and practical, sustainable fat loss strategies, emphasizing critical evaluation of online health advice.
Deep Dive Analysis
17 Topic Outline
Testosterone and DHT: Mechanisms and Gender Differences
Testosterone Replacement Therapy (TRT) in Women: Risks and Dosing
DHEA Supplementation: Effects on Men and Women
Progesterone's Role and Supplementation in Men and Women
Accurate Measurement of Testosterone and Estradiol
Rising Interest in TRT and Risks of Underground Sources
Clomid, Enclomiphene, and hCG in TRT: Trade-offs and Concerns
Addressing Low Testosterone: Diagnostic Steps and Lifestyle Factors
FDA's Category 2 Ruling on Peptides and Its Implications
Follistatin Gene Therapy and Myostatin Inhibition for Muscle Growth
Bodybuilder Strategies for Sustainable Fat Loss
Protein Ice Cream and Diet Hacks for Satiety
Impact of Prolonged Fasting on Hormones
Fat Loss Supplements: L-Carnitine, Caffeine, Yohimbine
Addressing Hypercortisolemia and Metabolic Dysfunction
Importance of Diet, Exercise, and Sleep for Body Composition
Debunking Health Misinformation and Charlatans Online
9 Key Concepts
Androgen Receptor
A protein that binds to androgens like testosterone and DHT, inducing gene expression for muscle protein synthesis and other anabolic actions in tissues, determining masculine characteristics.
Viralization
The development of male-pattern characteristics in a female, such as clitoral enlargement, voice deepening, and acne, often resulting from exposure to high levels of androgens like testosterone.
Steroidogenesis
The biochemical pathway in the body that synthesizes steroid hormones from cholesterol, leading to the production of glucocorticoids, androgens (like testosterone and DHT), and estrogens.
Selective Estrogen Receptor Modulator (SERM)
A class of drugs that selectively act as either agonists or antagonists on estrogen receptors in different tissues, with Clomid blocking estrogen receptors in the hypothalamus to increase testosterone.
Category 2 Peptides
A classification by the FDA for certain peptides, including BPC-157 and CJC-1295, indicating they are high-risk substances that cannot be sold by compounding pharmacies or through interstate commerce due to insufficient safety data.
Myostatin
A protein that inhibits muscle growth, with its knockout in animals leading to a 'double muscle' phenotype, and its inhibition being a target for increasing muscle mass.
Follistatin
A protein that inhibits myostatin, and its activation through gene therapy or direct injection is explored as a potential way to increase muscle mass.
Non-Exercise Activity Thermogenesis (NEAT)
The energy expended for everything we do that is not sleeping, eating, or sports-like exercise, which can subconsciously decrease during calorie deficits.
Alpha-2 Adrenergic Antagonist
A type of drug, like Yohimbine, that blocks alpha-2 adrenergic receptors, leading to increased adrenaline signaling and stimulatory effects, potentially aiding fat loss and energy.
15 Questions Answered
Testosterone is the primary androgen dictating muscle growth and anabolic activity in tissues for both men and women, though men produce about 10 times more. It also influences sexual maturation and differentiation.
High-dose testosterone in women can lead to viralizing symptoms like clitoral enlargement, voice deepening, and severe acne, which can be irreversible if not closely monitored and addressed quickly.
In men, DHEA supplementation shows no utility for increasing testosterone levels; at best, it may cause a spike in estrogen.
DHEA supplementation (e.g., 50 mg/day) can be useful for women, particularly those on combined oral contraceptives, as it has been shown to restore total and free testosterone levels to baseline.
Progesterone produces an array of anxiolytic (anti-anxiety) and sleep-aiding metabolite hormones, such as allopregnenolone, which can balance sympathetic drive and improve sleep.
Enzyme-based immunoassays for testosterone and estradiol can be significantly inaccurate, with LCMS (liquid chromatography-mass spectrometry) being the gold standard for more precise measurements, especially for estradiol which can be off by more than 2X.
Certain supplements like biotin can dramatically skew immunoassay results for hormones and thyroid values, making it important to stop them several days to a week before testing.
Long-term use of Clomid for TRT is not considered sustainable for vitality, as it involves chronic estrogen receptor antagonism in certain tissues, which can lead to issues like ocular problems, skewed lipid parameters, and unstable mood.
HCG can be used to mimic the pituitary's luteinizing hormone (LH) signal to the testes, helping to assess the testes' ability to produce testosterone and determine if hypogonadism is central (pituitary issue) or peripheral (testicular issue).
Adequate sleep, proper micronutrient intake (e.g., zinc, magnesium, vitamin D), sufficient macro intake relative to training stimulus, and consistent resistance training are crucial for optimizing natural testosterone levels.
The ruling places these peptides on a high-risk list, making them difficult for compounding pharmacies to produce and sell, and inviting legal scrutiny, though some research chemical sites may continue to operate under a 'research purposes only' pretense.
While myostatin knockout in young animals produces profound muscle growth, human trials with follistatin gene therapy have shown only modest increases in lean body mass (e.g., 2 pounds) and slight reductions in body fat, with some adverse metabolic effects.
A sustainable rate of weight loss is typically around 1% of body weight per week, or roughly 1-2 pounds per week, to avoid rapid adaptation and excessive hormone suppression.
Prolonged water-only fasting (e.g., 7-10 days) can profoundly suppress testosterone (e.g., from 500-600 to 100-200 ng/dL) and significantly impair thyroid function, increasing TSH and reverse T3 while decreasing free T3.
Caffeine is a reliable stimulant that can increase metabolic output, enhance gym performance, suppress appetite, and help attenuate energy deficits, with a generally safe upper limit of around 400 mg per day.
27 Actionable Insights
1. Prioritize Foundational Health Habits
Focus on diet, exercise, and sleep as they account for 90% of body composition and overall health outcomes; even performance-enhancing drugs yield minimal results without these core pillars.
2. Exercise Caution with Unregulated Peptides
Approach hormone replacement therapy and novel molecules with extreme caution due to prevalent irresponsible practices and unregulated products; prioritize foundational health habits over quick fixes promoted by influencers.
3. Opt for Accurate Hormone Testing
Choose LCMS (liquid chromatography-mass spectrometry) for testosterone and estradiol measurements, as enzyme-based immunoassays can be highly inaccurate, showing significant discrepancies.
4. Pause Biotin Before Blood Tests
Discontinue biotin supplements for at least a few days to a week before blood tests, as biotin can dramatically skew thyroid values and other hormone measurements, leading to inaccurate results.
5. Preserve Fertility with HCG on TRT
Men on TRT who desire to preserve fertility should consider concurrent HCG use to prevent testicular atrophy and maintain natural production, as recovery after long-term TRT can be arduous and not always successful.
6. Avoid Long-Term Clomid/Enclomiphene
Do not use Clomid or enclomiphene for long-term testosterone replacement therapy due to potential long-term estrogen receptor antagonism in various tissues and anecdotal reports of unstable mood.
7. Women: Dose Testosterone Cautiously
Women considering testosterone replacement must exercise extreme caution with dosing, as common recommendations often exceed natural physiological limits and can lead to irreversible masculinizing side effects.
8. Women: Monitor Testosterone Side Effects
Women using testosterone should meticulously monitor for side effects like clitoral enlargement, acne, facial hair, and voice changes, as some viralizing effects can be irreversible if not caught early.
9. Assess Testicular Health Before TRT
Before starting TRT, assess your testicular health and response by checking LH and FSH levels and potentially using HCG to gauge your testes’ ability to produce testosterone; this helps determine if hypogonadism is central or peripheral.
10. Optimize Natural Testosterone Production
Ensure adequate micronutrient intake (zinc, magnesium, vitamin D), sufficient macro intake relative to training demands, and proper recovery to optimize natural testosterone production, as deficiencies can significantly impact hormone levels.
11. Aim for Sustainable Weight Loss
Target a sustainable weight loss rate of no more than 1% of body weight per week (or about one pound) to avoid rapid adaptation, nutrient deprivation, and the risk of digging yourself into a metabolic hole.
12. Maintain High Protein Intake
Consume one gram of protein per pound of body weight daily, especially when in a calorie deficit, to preserve lean muscle mass and support muscle protein synthesis.
13. Gradually Adjust Calorie Deficit
Implement a gradual calorie deficit (e.g., 300 calories) and maintain it until weight loss plateaus for about a week, then make small, incremental adjustments (e.g., add cardio or reduce 100 calories) to avoid aggressive cuts.
14. Swap Calorie-Dense for Lighter Foods
To reduce calorie intake sustainably, replace calorie-dense foods with lighter options while maintaining food volume, such as lean chicken breast instead of red meat, or fat-free Greek yogurt.
15. Meticulously Track All Food Intake
For effective weight management, meticulously track all food intake, including sauces, drinks, and small tastes, by reading nutritional labels to become intimately aware of calorie and macro content.
16. Move After Meals for Fuel Partitioning
Engage in light physical activity, such as walking, after meals to improve fuel partitioning and blood sugar stabilization, which can optimize body composition.
17. Supplement Creatine for Performance
Supplement with creatine for enhanced gym performance, muscle volumization, and anti-catabolic effects, as it is considered the best over-the-counter supplement for performance and helps preserve muscle.
18. Use Caffeine for Energy & Appetite
Incorporated caffeine (up to 400mg daily) to reliably increase energy, enhance gym performance, and suppress appetite, especially when in a calorie deficit, as it is a well-studied and generally safe stimulant.
19. Make High-Protein Ice Cream
Utilize a Ninja Creami to create high-protein, low-calorie ice cream from whey isolate and sweeteners; this provides a highly satiating and delicious alternative to traditional desserts, aiding calorie restriction.
20. Eat Calories, Don’t Drink Them
To enhance satiety and reduce calorie intake, prioritize consuming calories in solid form over liquid, converting caloric beverages (excluding water) into slush or solidified formats where possible.
21. Use Diet Soda for Sweet Cravings
When in a calorie deficit and experiencing sweet cravings, opt for diet soda over calorie-rich desserts to satisfy a sweet tooth and avoid derailing body composition goals.
22. DHEA for Women on Oral Contraceptives
Women on combined oral contraceptives experiencing suppressed testosterone may consider supplementing with 50mg of DHEA daily to help restore total and free testosterone levels.
23. Individualize Progesterone Dosing for Women
For women using progesterone, aim to find an individualized dose (e.g., 50-100mg) that can be tolerated and provides benefits, as individual biochemistry varies significantly.
24. Progesterone for Men on TRT (Caution)
Men on TRT experiencing anxiety or sleep issues, especially with lower SHBG, might consider progesterone supplementation (50-200mg) to help balance sympathetic drive and mitigate disproportionately high free androgen levels.
25. DHEA Caution for Women with Normal Levels
Women with already normal DHEA and testosterone levels should be cautious about DHEA supplementation, as it often leads to common side effects like acne without significant additional benefits.
26. Yohimbine for Targeted Energy (Caution)
Consider Yohimbine (or alpha-Yohimbine) for targeted energy boosts and potential fat loss during intense calorie deficits or before cardio/training, but use with extreme caution as it can spike adrenaline and cause anxiety.
27. Consider Hunting for Lean Red Meat
For a budget-friendly and healthy source of lean red meat, consider hunting wild game like deer or elk, which can provide a year’s supply of unstressed, high-quality meat.
7 Key Quotes
It's viewed as such a taboo thing, even though at the end of the day, it is just a natural hormone that you produce.
Peter Attia
There's no FDA approved women's testosterone as well.
Derek
You don't even know what your ideal target is. Even if you were getting blood work, oftentimes it's totally skewed.
Derek
HRT is serious business. I do think a lot of people are doing it incorrectly, and I think there are a lot of really irresponsible people out there who are frankly just practicing dangerous medicine, if not veterinary medicine outright.
Peter Attia
You do not achieve even the outcomes from anabolics without the support of a great infrastructure of diet and training and sleep.
Derek
Just notable, by the way, for anyone watching, who's not a member of the drive, like this is why I pay for your membership is like the trust factor I have in your stuff is like above and beyond any piece of content I consume.
Derek
I don't know, man. Like, some of the products he sells, it's like he has a $140,000 red light bed.
Derek