#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

Feb 26, 2024 Episode Page ↗
Overview

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.

At a Glance
27 Insights
2h 38m Duration
17 Topics
9 Concepts

Deep Dive Analysis

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

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.

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What is testosterone's primary role in the body for both men and women?

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.

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What are the risks of high-dose testosterone use in women?

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.

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Is DHEA supplementation useful for men?

In men, DHEA supplementation shows no utility for increasing testosterone levels; at best, it may cause a spike in estrogen.

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Is DHEA supplementation useful for women, especially those on oral contraceptives?

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.

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What is the role of progesterone in women beyond reproduction?

Progesterone produces an array of anxiolytic (anti-anxiety) and sleep-aiding metabolite hormones, such as allopregnenolone, which can balance sympathetic drive and improve sleep.

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How accurate are different blood tests for testosterone and estradiol?

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.

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What can skew hormone blood test results?

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.

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What are the long-term risks of using Clomid for TRT in men?

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.

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What is the role of HCG in assessing testicular function before starting TRT?

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).

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What lifestyle factors significantly impact natural testosterone production?

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.

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What does the FDA's Category 2 ruling mean for peptides like BPC-157?

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.

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Does follistatin gene therapy effectively increase muscle mass in adults?

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.

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What is a sustainable rate of weight loss for most people?

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.

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How does prolonged fasting impact testosterone and thyroid hormones?

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.

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How effective is caffeine for fat loss and energy during a deficit?

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.

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.

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
10x
Testosterone production difference between men and women Men produce approximately 10 times more testosterone than females.
50 mg
DHEA supplementation dose for women on oral contraceptives Daily dose shown to restore total and free testosterone levels to baseline in women on combined oral contraceptives.
502 ng/dL
Peter Attia's testosterone immunoassay result Compared to 381 ng/dL via LCMS (gold standard).
41.3 pg/mL
Peter Attia's estradiol immunoassay result Compared to 18.3 pg/mL via LCMS (gold standard).
50 mg
Typical Clomid dose for TRT Daily or three times a week.
25%
Increase in muscle mass in mature mice with near complete myostatin block Achieved with >99% mRNA deletion of the myostatin gene.
~2 lbs
Lean body mass gain from follistatin gene therapy in human trials Reported in a phase one open-label trial.
~1%
Body fat reduction from follistatin gene therapy in human trials Reported in a phase one open-label trial.
1 gram per pound
Recommended protein intake for muscle preservation during deficit Of body weight, without fail.
1% of body weight
General rule of thumb for weekly weight loss Or 1-2 pounds per week for sustainable fat loss.
300 calories
Recommended initial calorie deficit Below maintenance to start a fat loss phase.
40% protein, 40% carbs, 20% fat
General macro split for fat loss A common ratio for sustaining hormone production and gym performance.
<2000 calories
Bodybuilder calorie intake (stage ready, natural, sub 200 lbs) Typical intake for natural bodybuilders weighing under 200 pounds when stage-ready.
2500-2600 calories
Bodybuilder calorie intake (stage ready, IFBB pro, 260 lbs) Typical intake for top IFBB professional bodybuilders weighing 260 pounds when stage-ready.
From 500-600 ng/dL to 100-200 ng/dL
Peter Attia's total testosterone drop after 7-10 day water fast Observed during personal experimentation with prolonged fasting.
From 2 to 4-6
Peter Attia's TSH increase after 7-10 day water fast Observed during personal experimentation with prolonged fasting.
From 3 to 1.5
Peter Attia's Free T3 drop after 7-10 day water fast Observed during personal experimentation with prolonged fasting.
From 12 to 32
Peter Attia's Reverse T3 increase after 7-10 day water fast Observed during personal experimentation with prolonged fasting.
10-15%
Oral L-carnitine bioavailability Requiring higher oral doses to achieve the same yield as injectable forms.
400 mg
FDA's recommended upper tolerability and safety threshold for caffeine Daily intake.
600 mg per week
Testosterone dose in the Boston study Used in a graded dose-response study, approximately 6x physiologic dose.
$300
Cost of whole genome sequencing today For 3 billion base pairs.
$600
Cost of Gary Brecka's gene testing For a limited amount of common SNPs.
$140,000
Cost of Gary Brecka's red light bed An example of an expensive product he sells.