If there was ever a time to load up on health products for the year, this is the week.

To save your valuable time & coin, I scoured, vetted & curated the ultimate list of top Amazon Prime Day deals to take advantage of this week (23 —25 June). As always, I’m only putting out products I use & trust.

Before you get into this year’s deals, reminder to review the guidelines we laid out how to navigate the Wild Wild West of the Amazon health marketplace – what scams to avoid, how to validate price history, & other tactics to save when browsing this week (or any time).

Here are the top 37 Phys approved deals for this year’s Amazon Prime Day.

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Protein

Powders

Levels Grass Fed Whey

My top preference for a grass-fed whey without artificial additives. Mixes easily & goes well in overnight oats and Greek yogurt parfaits.

$35.99 $44.99 — save 20%

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LEGION Whey+ Isolate

Top-tier isolate so it’s lactose-light and digests the best on this list. My pick on days I want to go easy on the gut. Naturally sweetened. Fully transparent label.

$47.23 $61.99 — save 24%

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Jocko Fuel Whey

Most cost efficient option with built-in digestive enzymes and probiotics. No added sugar. “Good” (*winks*…IYKY) post-lift protein option that doesn’t sit heavy.

$35.96 $44.95 — save 20%

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GHOST Whey

By far the best tasting protein on our list. Great flavor selection to diversify the homemade ice cream/Creami lineup.

$43.99 $54.99 — save 20%

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Bars

ALOHA Organic Protein Bars

A low sugar/no stevia or erythritol bar option. Shockingly good texture & taste for a minimal ingredient bar.

$20.36 $23.95 — save 15%

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Equip Prime Bars — Grass-Fed Beef Protein

Equip makes premier products across the board. A whole-food protein bar made from grass-fed beef, collagen, & tallow instead of the usual isolate-and-fiber-syrup formula.

$42.49 $49.99 — save 15%

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Pre-Workout & Energy

Gorilla Mind Pre-Workout

One of only a few pre-workouts I consistently come back to. Well-dosed and tastes exceptional (not too sweet).

$47.99 $59.99 — save 20%

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REDCON1 Total War

Efficaciously dosed & a budget pick with an insane deal this week. Tough to beat per serving.

$19.99 $44.99 — save 56%

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C4 Energy Drink (12-pack)

An all-time classic. But even better from the can. The grab-and-go option for days I skip the powder. Usually keep a couple in the gym bag as a just in case.

$21.36 $27.99 — save 24%

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Daily Stack Supplements

Nutricost Creatine Monohydrate

For you. For your sister. For your father. For your grandma. Everyone can benefit from the purest form of creatine. 5—10g daily, each & every day.

$16.60 $21.50 — save 23%

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Qunol Mega Ubiquinol CoQ10

Ubiquinol is the pre-reduced form so your body skips the conversion step regular CoQ10 forces on it. I run it for mitochondrial & cardiovascular support. Especially high ROI if you’re > 40 or on a statin.

Find out why ubiquinol is the superior form of CoQ10 here:

$24.52 $32.99 — save 26%

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NOW Foods NAC with Selenium

Direct precursor to glutathione (the master antioxidant) which is why it turns up in everything from liver to lung research. I cycle NAC for detox capacity & overall recovery load.

Also a critical & proven tool for the nicotine exit protocol:

$9.31 $12.70 — save 27%

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Carlson Cod Liver Oil

Preferred natural method of DHA/EPA. Omega-3s plus naturally occurring vitamins A & D in one liquid. Norwegian-sourced & clean. Lemon makes a teaspoon actually go down easy.

$26.66 $31.37 — save 15%

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Objective Nutrients Thiamax — Vitamin B1 (TTFD)

TTFD is a fat-soluble form of B1 that crosses into cells & the brain, unlike standard thiamine. If you run on stress, carbs, and caffeine you burn through B1 fast. Been using this during my most recent cutting phase and can notice a clear difference in afternoon energy & mental clarity. Zero fillers.

$22.78 $26.85 — save 15%

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Electrolytes & Minerals

Zeal Electrolyte Powder

Solid electrolyte ratios & incredible value for a ~zero calorie electrolyte powder. I use it for training & sipping throughout the workout to keep electrolyte & hydration dialed in.

$24.45 $34.95 — save 30%

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Transparent Labs Hydrate

My cleaner electrolyte pick with added taurine & coconut water powder. No sugar or dyes. Third-party tested. Great for cardio & lifting days alike.

$23.99 $29.99 — save 20%

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Jigsaw Health Adrenal Cocktail

Whole-food vitamin C from acerola plus potassium & minerals — the “adrenal cocktail” people use to steady energy and handle allostatic stress loads. Usually reserve this one for the winter mornings or post-sauna. Food-form C behaves differently than synthetic ascorbic acid.

$24.35 $39.97 — save 39%

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Sleep & Recovery Supplements

Centenarius Premium Glycine Powder

3—5g before bed is the vivid dreams elixir. Regulates core body temperature down & improves sleep onset. The highest quality glycine out there & you’ll taste the (sweet) difference.

$23.99 $29.99 — save 20%

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Solaray Magnesium Glycinate

High chance you’re deficient in it (especially if you’re in stressful conditions often). Best budget pick I found this week among the select few brands I trust for high quality magnesium.

Check out the complete guide to magnesium supplementation here:

$15.63 $22.99 — save 32%

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PreSleep Natural Sleep Powder

A melatonin-free sleep stack combining my basic sleep stack — magnesium + glycine + L-theanine. Win-win-win.

$39.99 $49.99 — save 20%

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Nutricost Taurine Powder

We are going to be talking about taurine next year the way most talk about creatine today. One of the most underrated aminos that supports cell hydration, calcium handling in muscle, & has a calming effect on GABA/glutamate balance. Bulk powder makes it pennies/serving.

$10.36 $12.95 — save 20%

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Nutricost L-Theanine

Ol’ calming reliable at even small doses of 200mg (& particularly powerful when you trend up to 1g). Smooths the jitters when stacked with coffee and takes the edge off a wired but tired monkey brain at night.

$15.96 $19.95 — save 20%

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NOW Foods Inositol Powder

One of my favorite current tools for reducing nighttime anxiety & racing thoughts. 3g in the evening sublingual has been the sweet spot to calm the monkey brain. Powder form makes the higher effective doses affordable.

Find out why this is the most overlooked supplement you’re not using:

$25.60 $32.00 — save 20%

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Gut Health Supplements

Revive MD Fiber

A good-tasting psyllium-based fiber. Great in Greek yogurt parfaits. Feeds your gut bacteria. Improves digestion. Stabilizes post-meal glucose spikes.

$20.99 $27.99 — save 25%

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Doctor’s Best PepZin GI

Zinc-L-carnosine is a compound supporting the gut lining. Not a general “gut health” supplement. My go-to (alongside oral BPC-157 & glutamine) when my stomach needs repair support.

$17.24 $23.99 — save 28%

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Nutricost Zinc Carnosine

Same active compound as PepZin GI at a higher dose & lower price. More of a value pick once you know zinc-carnosine works for your gut.

$15.96 $19.95 — save 20%

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Health Environment Products

BestQool Red Light Therapy Panel

I’ve had my BestQool for over 2 yrs now and it’s still functioning perfectly. This one is just large enough to use on any sore areas post-training (usually the legs) and on my face. Best value for a reliable red/NIR panel in a sea of scam/overpriced products.

$152.61 $189.00 — save 19%

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Loop Experience 2 Earplugs

Reusable. Comfortable. Discreet. Durable. I enjoy them for focus around a noisy house & sleeping. Owned mine for 4+ yrs now and they’re still in the same condition I got them in.

$27.95 $34.95 — save 20%

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Breathe Right Nasal Strips — Extra Strength

An elite nighttime sleep quality hack — nasal breathing improves sleep quality and is the cheapest snoring fix I’ve found. Mechanically opens your nasal passages so you breathe through your nose.

$15.03 $20.99 — save 28%

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runquiz Amber Incandescent Bulbs

Now that they’re back on the market — a no-brainer switch. Swap these into the lamps you use after sunset. Cheap circadian hygiene hack.

$19.19 $23.99 — save 20%

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Sleep ZM Blue Light Blocking Glasses

The cheapest, most effective circadian hack to improving overall sleep quality → amber/red lenses block isolated blue light from screens. I put them on a couple hours before bed & pair them with the f.lux app & amber bulbs.

$37.98 $49.99 — save 24%

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Training Gear

Lacuffy Walking Pad (6% Incline)

No excuse to not hit 15k steps/day with this (& a standing desk). Walk on it during calls & while reading. The most underrated lever for the last few pounds of any legitimate cut phase.

$94.99 $117.99 — save 19%

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Abiarst Ab Roller Wheel

When performed properly, ab rollouts will cook your core muscles. And you can do it at home anytime. Easy add to the home office training gear arsenal.

More on how to efficiently build an elite set of abs:

$13.42 $19.99 — save 33%

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UUJOME Hand Grippers (Adjustable Set)

Easy at your desk style training for forearm work. Zonkfest meetings become productive forearm training sessions.

$20.89 $24.99 — save 16%

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Biomarkers

iHealth Smart Blood Pressure Monitor

Blood pressure is the canary in the cardiovascular coal mine. No excuse not to track it at home and you’ll catch problems years before a routine visit would. This cuff is Bluetooth-synced & fits well for most.

$27.99 $49.98 — save 44%

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Kitchen Optimizers

Ninja Air Fryer & Toaster Oven Combo

Highest ROI kitchen gear I own. Elite deal at half price this week. The easy way to avoid some of the common toxic elements in the typical air fryers. 10-in-1 type & it’s big enough to meal prep potatoes/sweet potatoes for the week.

$199.99 $399.99 — save 50%

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Ninja CREAMi

Hands down the greatest nutrition hack I’ve adopted in the last couple years. The tool behind every great high protein dessert. And I’ve been using it way more than I initially expected. You’ll wonder how you ever operated without it.

$169.99 $219.99 — save 23%

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Etekcity Food Kitchen Scale

High chance you’re underestimating portions by eye. Have now had mine for 3+ yrs. Reliable. Durable. Simple & gets the job done…your cutting phase will thank you.

$9.99 $13.99 — save 29%

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VocVoi Stainless Steel Pan

Time to toss the toxic nonstick pans. Learning the art of cooking with stainless steel takes ~1 week. After that, it’s clockwork and a high ROI health investment.

$28.47 $39.99 — save 29%

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Evoloop Rapid Egg Cooker

My convenient (lazy) method to hit my daily egg intake if I need to meal prep or I don’t want to pan fry.

$23.99 $29.99 — save 20%

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Oliva Dorado Organic Extra Virgin Olive Oil

The purest & best-tasting extra virgin olive oil I’ve ever used. Single-origin, early-harvest, polyphenol-rich. Will never go back to another brand. It is that good.

$38.40 $48.00 — save 20%

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OLD BAY Seasoning

The S-tier way to make high-protein dishes much less boring (eggs, fish, chicken, shrimp). Don’t neglect the king of seasonings.

The proper way to leverage Old Bay:

$7.62 $10.91 — save 30%

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Bob’s Red Mill Gluten-Free Rolled Oats

The key to gluten-free overnight oats. Ditch the Quaker slop.

$10.17 $11.96 — save 15%

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Skin & Low-Tox Personal Care

Native Body Wash

Clean body wash without the sulfates, parabens, silicones, or dyes most brands lean on. Minimal ingredient (12) formulas & still manages to work well/smell great.

$9.09 $12.99 — save 30%

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Mirror Skin Copper Peptide Serum

The only GHK-Cu copper peptide I’ve leveraged in the last year (the market on Amazon is egregious — avoid others). I run it at night with 15—20 min of red/NIR directly to the face. Incredible difference maker on skin clarity after a couple months of consistent usage.

$74.00 $88.00 — save 16%

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Dr Teal’s Aluminum-Free Deodorant

Most suck…but this is the aluminum-free deodorant I’ve settled on that works best → magnesium & arrowroot handle odor well. An easy low-tox swap I’ve been using for years.

$14.01 $16.49 — save 15%

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Oral Health

NOBS Toothpaste Tablets

Nano-hydroxyapatite instead of fluoride. Remineralizes enamel through the same mechanism (without the fluoride toxicity). Plastic-free, travel-friendly tablets. Another product you’ll use once and you’ll never return to your typical toothpaste. (& your dental bill will reflect accordingly).

$38.24 $44.99 — save 15%

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Spry Xylitol Gum

A staple cure to bored mouth & curing cravings. Added bonus of xylitol after meals — the bacteria that cause cavities can’t metabolize xylitol so chewing it starves them & boosts saliva.

$8.49 $9.99 — save 15%

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Hope this one saves you guys some time & money this week on a lot of products you’d otherwise be scooping up at normal prices.

Reminder: the Prime Day Deals end on 25 June.

Happy hunting. And until next time, stay after it.

Your friend,
Phys

The Phys Debrief · #03
Practical takeaways & the latest research from the health space’s most valuable long-form content, without the rest.

Centralized medicine has defaulted to handing you a reference range and calling it a day. Dr. Deep takes a refreshingly different approach.

His thesis is simple: the 40—50 decade is when entropy starts winning and the people who thrive through it are the clear thinkers who stop outsourcing their health to a system built for averages.

An rising voice in the longevity space, Deep thinks in mental models, ratios, & root causes, rather than single value biomarkers. So you can imagine why we chose to debrief this one.

Contents:

• In 1 Sentence

• In 250 Words

• Practical Takeaways

• Episode Blueprint

• Where to Listen & Watch

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In One Sentence

Midlife is a high-entropy inflection point, and surviving it well means abandoning population-based “normal” ranges and single-metric thinking in favor of individualized targets, root-cause anti-inflammatory living, and data used to investigate.

In 250 Words

Dr. Deep’s organizing idea: modern medicine optimizes for the average patient, but the average patient is getting sicker so “normal” is a moving target you shouldn’t aim at. 70% of Americans are overweight or obese. 60% are diabetic or pre-diabetic. A testosterone of 300 & a testosterone of 900 are both “normal” and represent completely different lives. His clinic builds tighter, individualized ranges instead.

The episode’s most useful reframes are diagnostic. High cholesterol alone doesn’t cause heart attacks — you also need damaged vascular endothelium, which comes from high blood pressure, smoking, diabetes, or inflammation. Low VO2 max carries a far larger mortality signal than a modestly elevated LDL. A lean marathoner can still be insulin-resistant and over-trained into chronic high cortisol because muscle is the glucose sink and cardio alone doesn’t build it. Fasting insulin is a leading indicator of diabetes. A1c is a lagging one that fires after damage is done.

“Inflammaging” is chronic low-grade inflammation from poor sleep, stress, visceral fat, and constant sympathetic activation that smolders until it ignites real disease. The fix is root-cause, not symptom suppression.

Practically: Pair carbs with protein and fat. Run a CGM for a month to learn your responses. Use the 3-2-1 sleep rule (no food 3h before bed, no screens at 2h, limit fluids at 1h). Use wearables to build body literacy, then stop letting them override how you actually feel.

Practical Takeaways

Mental Models (first principles)

• Treat “normal” as a warning (not the objective:) Population reference ranges drift with the population’s health, but the population is getting sicker. A result inside the “normal” band can still be far from optimal. Ask for individualized targets.

• Think in ratios and systems (not single numbers): Sex hormones especially only make sense in relation to each other (testosterone to estrogen, plus SHBG), and “biological age” of one organ is meaningless if another is failing. Stop optimizing one metric in isolation.

• Use data as a prompt to investigate: A bad biological-age score or a high HRV-variance reading is a signal to go check the engine. Beware false precision — obsessing over two-beat HRV swings isn’t useful.

Cardiometabolic Screening

• Get apoB measured, not just cholesterol: apoB counts the number of atherogenic particles (”cars and trucks on the highway”). Standard cholesterol counts how full each particle is, which matters less. Particle number is what drives the traffic-jam event.

• Track fasting insulin as your early-warning light: Elevated fasting insulin means your pancreas is already working overtime — a leading indicator of impending diabetes. Hemoglobin A1c is a lagging indicator that confirms damage already done. Check insulin to get ahead of it.

• Don’t let leanness or fitness reassure you: A great VO2 max can coexist with low muscle mass, chronic hypercortisolemia, hyperglycemia, & insulin resistance. “Lean” is not “metabolically healthy.” Quantify the hidden risks instead of eyeballing them.

• Weigh VO2 max heavily in your heart-risk picture: Low cardiorespiratory fitness carries a mortality hazard ratio in the same range as (or larger than) smoking or diabetes, far above a modestly elevated LDL. Building aerobic capacity is one of the highest-leverage moves available.

Muscle & Metabolic Flexibility

• Build muscle as a glucose sink: Muscle pulls blood sugar into productive storage instead of letting it glycate and damage tissue. Cardio alone doesn’t do this. If you only train endurance, you’re leaving a major metabolic lever untouched.

• Mind muscle loss on GLP-1s: Rapid weight loss on GLP-1 / weight-loss drugs can strip muscle along with fat, which may undercut the same glucose-sink protection — a reason to pair these drugs with resistance training and protein.

• Avoid naked carbs: Pair carbohydrates with protein and fat to blunt glucose spikes. Run a CGM for at least a month to learn your personal responses (including how poor sleep and acute stress spike glucose in real time) then apply the lesson without wearing it forever.

Inflammaging & Recovery

• Hunt the root cause of inflammation: Smoldering low-grade inflammation from poor sleep, chronic stress, visceral fat, or autoimmune conditions is the kindling for most age-related disease. Suppressing inflammation (i.e. via a hyperbaric chamber) while leaving the cause in place is a half-measure.

• Shift the autonomic balance toward vagal tone: Modern life keeps you in chronic sympathetic activation (blue light, doom-scrolling, stress), which feeds inflammation. The highest-yield move is removing the offending stimulus without adding a hack.

• Run the 3-2-1 sleep rule: No food 3 hours before bed, no screens 2 hours before, limit fluids 1 hour before. Dr. Deep calls this the hidden unlock for the over-stimulated executive archetype and screens at the 2-hour mark are the hardest and most important one to hold.

Tools & Diagnostics (how to actually use them)

• CGM — worth a month, not a lifetime: Available over the counter now. Use it to build intuition about your glucose responses, then stop before it makes you neurotic.

• Full-body MRI — bullish, with a caveat: Prices are collapsing (Ezra around $500, headed toward DEXA-like ubiquity). The real prerequisite is a clinician who has prepped you for incidental findings so a benign spot doesn’t terrify you. Data in the wrong hands is “a monkey with a machine gun.”

• Wearables — let how you feel win: Sleep trackers and Whoop are useful for a month or so to learn your patterns, but they fill in gaps and estimate (the Apple Watch VO2 max formula reportedly traces to one tiny old study). When the tracker and your felt experience disagree, trust your body. Letting the device dictate how you feel is “orthosomnia.”

Episode Blueprint

[00:00:00–00:08:10] Intro: Dr. Deep & the Velocity Health Model

Key Points

• The guest is Dr. Sandeep “Deep” Palakodeti, MD/MPH, founder of Velocity Health and author of The Ultimate Asset. The MD/MPH combination gives him both the population bird’s-eye view and the individual clinical lens, which is the source of his core critique.

• His framing of the system: physicians become “widgets in a machine” with ~10 minutes per patient, structurally unable to do prevention or deep individualized care.

• Velocity is pitched as a digitally native concierge precision-medicine clinic, licensed in all 50 states — “your doc in your pocket” for high performers who travel and want quarterly 90-minute visits rather than rushed appointments.

• The macro case for urgency: ~70% of Americans overweight or obese, ~60% diabetic or pre-diabetic, with cancer and neurodegenerative disease climbing. “What we’re doing is obviously not working.”

[00:08:10–00:12:55] The Concierge Awakening & the “Not-Normal” Patient

Key Points

• Rapid hair thinning in host’s late 20s sent him through urologists and endocrinologists with no answers, until a cash-pay clinic caught a lifelong-missed Hashimoto’s, diagnosed low testosterone, and walked him through hCG, fertility preservation, and vitamin D in a single unhurried visit.

• High performers who can model a portfolio for decades but have no system for their own health, and who don’t fit the “normal patient” mold a 10-minute visit assumes.

• Fringe communities (i.e. bodybuilding forums) often run 10–20 years ahead of mainstream medicine on practical protocols.

[00:12:55–00:16:37] BS or Not: Slower Metabolism & Broken Lab Ranges

Key Points

• “Midlife means a slower metabolism no matter what” — BS. Elite marathon and endurance performance often peaks later than sprint sports because mitochondrial biogenesis takes years to build. Midlife can be an inflection point toward peak health.

• The 40–50 decade is real “peak entropy”. Things break down faster and require more intentional effort to hold together.

• Lab reference ranges are population-derived so they drift as the population changes. Median testosterone for a 40-year-old male was ~700 forty years ago; it’s closer to ~400 now, yet the “normal” band widened to accommodate the decline.

• A T of 280–300 and a T of 900 are both “normal” and are completely different lives.

[00:16:37–00:18:30] Does High Cholesterol Actually Cause Heart Disease?

Key Points

• High cholesterol is a single input. You need both atherogenic particles and damaged vascular endothelium for the heart-attack cascade to start.

• Endothelial damage comes primarily four ways:

  • High blood pressure

  • Smoking

  • Diabetes

  • Chronic, low-grade inflammation

• On relative weighting: low VO2 max carries a ~4x hazard for cardiac events vs. ~1.2x for elevated LDL-C. Control the bigger levers and there’s likely a healthy middle range for cholesterol rather than a “lower is always better at all costs” mandate.

• A coronary calcium score of 0 in a young person can be falsely reassuring — soft plaque hasn’t had time to calcify into the hard plaque the scan detects.

Studies referenced

• Association of Cardiorespiratory Fitness With Long-Term Mortality Among Adults Undergoing Exercise Treadmill Testing (JAMA Network Open, 2018; Mandsager et al.) — In 122,007 patients, low cardiorespiratory fitness vs. elite carried an adjusted all-cause-mortality hazard ratio of ~5.0, exceeding smoking, diabetes, and coronary artery disease, with no observed upper limit of benefit.

[00:18:30–00:21:26] The Marathon Runner Heart-Attack Paradox

Key Points

• A 50 yr old patient in good shape who ran a half-marathon had a heart attack anyway.

• Two failures stacked: 1) too little muscle (muscle = glucose sink that keeps blood sugar from glycating & damaging tissue) and over-training into chronic high cortisol & chronic hyperglycemia → producing insulin resistance.

• “Just because you’re lean doesn’t mean you’re healthy.” Metabolic health has many independent levers. You can be excellent on a handful and in the dumpster on the rest. Eyeballing someone tells you almost nothing.

• Concern flagged for GLP-1 / weight-loss-drug users: rapid loss of weight can mean loss of muscle, potentially eroding that same glucose-sink protection.

[00:21:26–00:24:04] Is “Biological Age” Just a Gimmick?

Key Points

• The absolute number is largely unproven. No one has run the multi-decade follow-up to confirm a “15 years younger” score means you actually live longer.

• Directionally useful, though. Most tests amalgamate many data points so a sudden jump after a bad 6 months is a signal to go investigate.

• Per-organ “ages” are misleading when siloed. A 22-year-old immune system is irrelevant if your cardiac age is 74. The body is one system.

• The space loves data, but should temper it with humility about false precision. “Everyone’s neurotic age is very high.”

[00:24:04–00:26:39] Explain It to My Mom: apoB & Fasting Insulin

Key Points

• apoB analogy: Arteries are highways. A heart attack is a crash/traffic jam. What causes jams is the number of cars and trucks (not how many passengers are inside). apoB counts vehicles (particles). Cholesterol counts passengers (cargo), which matters far less.

• Fasting insulin analogy: When you eat too much sugar it sits in the blood and damages vessels. Insulin pushes it into safe storage. Elevated fasting insulin means the pancreas is working overtime — a leading indicator of impending diabetes.

• Hemoglobin A1c is a lagging indicator: By the time it’s high, the damage is already underway. Checking fasting insulin gets you in front of the disease process.

[00:26:39–00:28:14] What Is “Inflammaging”?

Key Points

• Inflammaging = chronic low-grade inflammation → the “little smoldering fires” all over the body. Driven by poor sleep, high stress, autoimmune conditions, & excess visceral fat.

• Those baseline fires are what let other disease processes catch and spread. Put them out and it’s much harder for downstream disease to take hold.

• On suppressing inflammation without fixing the cause: Always pursue the root cause.

[00:28:14–00:30:01] Vagal Tone & the 3-2-1 Sleep Rule

Key Points

• The body runs on a balance between sympathetic activation and parasympathetic “rest and digest.” Modern life (blue light to midnight, chronic stress, doom-scrolling) keeps us over-activated, which drives inflammation and heart disease.

• The first move to raise vagal tone is to remove the offending stimulus, not to add a gadget or supplement.

• The 3-2-1 sleep rule:

  • 3 hours before bed = Last meal

  • 2 hours before bed = Screens off

  • 1 hour before = Fluids limited 1 hour before

[00:30:01–00:37:01] The Health-Trends Tier List: CGMs, MRIs & Wearables

Key Points

• Metabolic flexibility — S tier. The single biggest thing. Avoid naked carbs. Pair carbs with protein and fat. Consider a CGM for at least a month.

• Stem cells / PRP — A tier on promise. Still early on data. Bullish long-term but not yet proven.

• CGM — A tier for short-term use. Great for learning how sleep and stress move your glucose, available OTC, but easy to get neurotic about.

• Full-body MRI — A-to-B tier. Bullish as prices crater (Ezra ~$500), but only valuable with a clinician who preps you for incidental findings. The “find stuff we don’t know what to do with” objection is really a failure of the doctor-patient relationship.

• Wearables / sleep trackers — Useful for ~a month to build body literacy, then optional. They estimate and fill gaps. How you feel wins. Letting the tracker dictate your mood is “orthosomnia.”

[00:37:01–00:39:46] Your Evolutionary Duty in Midlife

Key Points

• The closing reframe: Why do humans live well past reproductive age when most male animals don’t? The elephant/wolf analogy — elder “institutional knowledge” (where the distant watering hole is) protects the whole tribe.

• The leaders of consequence (CEOs, governors, legislators) cluster in the 50–65 decade, exactly when peak biological entropy sets in. Failing to fight that decline systematically is, in his framing, a failure of duty to the people who depend on your knowledge.

• Whether you DIY or hire a team, the mandate is the same: Arm yourself with real information and build a system around your health instead of waiting for the system to fail you.

Listen & Watch

• YouTube

• Spotify

• Apple Podcasts: Down to Health

• Where to find Dr. Deep:

  • Velocity Health: velocityhealthclinic.com

  • Book: The Ultimate Asset

  • His podcast: The Ultimate Asset

We’re pushing out way more content on our paid side (some new n=1 experiments + a few new protocols you’re not going to want to miss).

All of which is made possible by you guys here on Substack. And we couldn’t be more grateful for the continued support.

More to come in the next few weeks. Stay after it until then.

Subscribe now

Your friend,
Phys

Most recipe sites have become insufferable.

They’re tests of patience wrought full of ads leaving you scrolling for 12 min before you actually land on anything close to a recipe.

Inspired by my own personal annoyance, we’re kicking off the Phys Recipe Series that will follow a simple template. I’ll give you the trifecta:

• Ingredients

• Deliberate step-by-step with some photos

• Nutritional breakdown (macros + micros)

Nothing more. Nothing less.

No better way to start than a family favorite (& new favorite of many in our health space).

This one is long overdue.

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What Even is Old Bay?

If you’re a Maryland/Chesapeake Bay area native, you already know the deal.

If you’re not, a quick primer: Old Bay is a celery-salt-based seasoning blend → mostly celery salt, paprika, and black/red pepper, with some background notes of mustard, allspice, ginger, cardamom, & cinnamon. It’s salty…so don’t add any more until you’ve tasted it.

At a Glance

• Yield: 3 lbs (~6 servings)

• Prep Time: 10 min (cubing 3 lbs is the bulk of it; oiling & seasoning are quick)

• Cook Time: 30–35 min

• Total Time: 45 min

Ingredients You’ll Need

• 3 lbs sweet potatoes = ~4 medium (one of the most budget friendly hacks out there → $3.99 at Costco for this 5 lb bag)

• 3 Tbsp extra-virgin olive oil (a light coat only — see Step 3)

• 3 Tbsp Old Bay seasoning

• 1 tsp ground cinnamon (go organic)

• 1 tsp garlic powder (recommended for depth)

• A few cracks of fresh black pepper (Old Bay already has some)

Step-by-Step

1. Preheat the oven to 425°F (220°C). Line two large sheet pans with parchment paper.

2. Cut the sweet potatoes into ¾- to 1-inch irregular cubes (skin on — excellent for texture, fiber, & nutrients). Keep pieces roughly uniform so they cook evenly.

Note: Be sure to trim off the ends.

3. Lightly oil. Place cubes in a large bowl and drizzle with the 3 Tbsp EVOO. Toss gently until every piece has a thin sheen — no pooling at the bottom of the bowl. Intention is a light coat here.

4. Season. Sprinkle the Old Bay, cinnamon, garlic powder, and black pepper over the oiled cubes. Toss thoroughly until every piece is evenly coated and the color looks like the photo.

5. Spread across two pans. Divide the cubes between both parchment-lined pans in a single layer with a little space between pieces. Crowding steams them instead of roasting them (& you lose out on the crispy edges). This volume needs two pans; don’t force it onto one.

6. Roast for 30–35 minutes, flipping and tossing once at the ~15-minute mark. If your oven runs uneven, rotate the pans top-to-bottom when you flip. They’re done when fork-tender inside with crispy, caramelized edges & deepened color. Time will vary based on cube size & oven, so go by look and feel.

7. Finish. Straight out of the oven, toss with an extra pinch of cinnamon and Old Bay for brightness and aroma. Serve immediately.

8. Optional added bonus → resistant starch. Cook, then cool the potatoes in a glass container overnight. Cooling retrogrades the starch (converting some into resistant starch, which feeds gut bacteria and blunts the glucose response). Reheat in an air fryer for 5–8 minutes to restore the crisp.

Learn more about how to leverage this process here:

Nutrition Breakdown (per serving)

Approximate values for 1 serving. Recipe yields ~6 servings.

Macros

✔ Calories: 230 kcal
✔ Protein: 3 g
✔ Total Carbs: 38 g
✔ Fiber: 6 g
✔ Net Carbs: 32 g
✔ Fat: 8 g

Notable Micronutrients & Relevance

✔ Vitamin A (~18,000 IU, 380%+ DV): One of the densest beta-carotene sources there is — supports vision, immune function, and skin.

✔ Potassium (~450 mg): Key electrolyte for blood pressure regulation & muscle function. Balance K:Na to ~2:1 ratio.

✔ Fiber (~6 g): Feeds gut bacteria and slows glucose absorption. Cook-and-cool step adds resistant starch on top.

✔ Vitamin C (~20 mg): Survives roasting partially. Supports collagen synthesis and immune function.

✔ Sodium (~400–600 mg): From the Old Bay.

As promised, we’ll be running plenty of these easy-to-prep meals in the future.

Remember to support the BTP publication while you’re here. You fuel each week.

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Until the next rep, stay after it. And we’ll see you next week.

Your friend,
Phys

The Phys Debrief · #02
Practical takeaways & the latest research from the health space’s most valuable long-form content, without the rest.

No serious metabolic health discussion can happen without an emphasis on the information processes of the body: mitochondria.

Right now, there’s no better individual to hit this topic than Chris Masterjohn, who runs the mitochondrial testing company Mitome and has spent 20+ years on the biochemistry of nutrition.

Masterjohn’s underlying thesis: mitochondrial energy production is what builds, maintains, repairs, and moves everything in the body.

Dave Feldman, the engineer behind the lipid energy model and the keto-CTA trial, hosted a dense one released earlier in the week. One we’ve made as digestible & practical as possible and extracted a plethora of hidden gems in here from both of these guys.

Contents:

• In 1 Sentence (30 sec)

• In 250 Words (1 min)

• Practical Takeaways (4 min)

• Episode Blueprint (11 min)

• Where to Listen & Watch (30 sec)

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In One Sentence

Mitochondrial energy production is the upstream determinant of most health and disease because nearly every cellular process that protects you (clearing cholesterol into cells, activating immune cells, defending membranes from oxidation) is an active, ATP-dependent process, which reframes high LDL, plaque, seed-oil damage, and even inflammatory disease as downstream symptoms of bottlenecks in energy metabolism rather than primary causes.

In 250 Words

The organizing lens is that movement implies energy. The LDL receptor pulling cholesterol into a cell, a T-cell activating to kill cancer, an endothelial cell chaperoning a lipoprotein across its wall — all are active processes powered by ATP from the mitochondria. Treat mitochondrial function as the root system and most “diseases of high markers” look different.

On atherosclerosis, Masterjohn and Feldman largely converge: native LDL concentration is not the primary driver. Damage to the particle is. Oxidation of polyunsaturated fats in the LDL membrane, and the LDL aggregation that follows, is what drives macrophage uptake and plaque. Plaque is framed as a containment response, dynamic and at least partly reversible if you remove the conditions that created it.

This is why seed oils harm. Their polyunsaturated fats are an oxidative liability: they load your membranes and lipoproteins with the fatty acids most vulnerable to peroxidation, and aging guarantees the oxidative stress. The only two long-term, large, double-blind RCTs ever run point toward harm for heart disease and cancer.

A second theme runs throughout: research is mostly broken. Short trials get extrapolated to long-term claims, “linked” hides whether an effect went up or down, peer review is single-blind theater, and trials stopped early for benefit exploit regression to the mean.

Practical bottom line: support the mitochondria first, minimize the most oxidizable fats, and treat dramatic short-term findings as likely to shrink.

Practical Takeaways

Mental Models (first principles)

• Treat movement as a tell for energy demand: If a biological process requires movement, whether pulling cholesterol into a cell, activating a T-cell, or transporting a vitamin, it requires ATP, which means it depends on mitochondrial function. Use this as a default lens: when a marker is off, ask what energy-dependent process upstream might be the bottleneck.

• Read diagrams as snapshots of dynamic processes, not static endpoints: Most bad mechanistic reasoning treats a textbook figure as the final state. Molecules have a distribution of kinetic energy and interact stochastically; what goes into a space (an oxidized LDL particle in the artery wall) can also come back out. Assume reversibility by default.

• Calibrate your confidence to the evidence and say so out loud: Distinguish wild speculation from mechanism from observational association from RCT, and label which one you’re standing on. The failure mode in nutrition is using vague language to smuggle a causal claim you won’t defend openly.

• Expect dramatic short-term findings to shrink (regression to the mean): A huge effect in a first or short study is usually supplanted by less impressive results later, and the larger the follow-up, the smaller the effect. When you see something dramatic, your base case should be that it gets less dramatic with more data.

Atherosclerosis & the lipid debate

• Target particle damage, not just particle count: The model both experts converge on is that oxidation of polyunsaturated fats in the LDL membrane, and the LDL aggregation it promotes, drives macrophage uptake and plaque — not the native LDL concentration itself. Lowering oxidizable substrate and oxidative stress is the lever, not chasing the number in isolation.

• Mind your saturated-fat-to-choline ratio: Phosphatidylcholine is the primary anti-aggregation molecule on the LDL particle and is fully dependent on dietary choline, an essential nutrient. The more saturated fat in the diet, the more choline you need — a driver Masterjohn has long tied to fatty liver as well. Egg yolks and liver are dense choline sources.

• Don’t throw out coronary calcium, but know its limit: The calcium that shows up on a CAC scan is macro-calcification, which is relatively stabilized. The micro-calcifications that make a fibrous cap brittle and rupture-prone don’t show on imaging. CAC can correlate with the process without being the thing that determines whether a plaque breaks.

• Plaque progression is largely driven by existing plaque: Once you have plaque you tend to get more, but mainly because the conditions that created it are still present. Remove those conditions and the animal literature supports regression. Plaque is a situational best-effort response, not a one-way ratchet.

Seed oils & PUFAs

• Treat seed oils as an oxidative liability, not an acute poison: Their polyunsaturated fats don’t damage you on contact. They make your membranes and lipoproteins more vulnerable to oxidative damage that aging then guarantees. The “house of glass” framing: fine until something throws a stone, and aging always eventually throws stones.

• It’s the bis-allylic carbon, so PUFAs are the real exposure: The carbon sitting between two double bonds is what’s highly vulnerable to peroxidation, which is why polyunsaturated (not monounsaturated) fats carry the liability. You still need essential PUFAs in small amounts. The problem is high chronic intake, not their existence.

• If you eat something daily, make it the highest-quality fat you can: Masterjohn’s practical heuristic on the “dose makes the poison” question — occasional canola in a salad dressing is trivial, but anything that becomes a base fat in your daily diet should not be a seed oil. The harm is a function of chronic membrane loading over years.

• Weight your evidence toward long, large, blinded trials: The short trials (8–12 weeks) tend to show metabolic benefit from seed oils. The multi-year trials trend neutral-to-harmful for heart disease and increased for cancer. When short- and long-term data conflict in nutrition, the long-term data wins.

Biomechanics, longevity & inflammation

• Train movement quality, not just cardio, for longevity: Cardiorespiratory fitness is real but probably overweighted. Elite athletes in sports demanding excellent joint function and biomechanics (pole vault, gymnastics) outlive the population by ~8 years versus ~2–3 for runners/cyclists. The hypothesis: high-quality biomechanics and extracellular matrix may support both immune surveillance against cancer and resistance to inflammatory disease.

• For Crohn’s, internal vs. external pressure is an underrated axis: A leading genetic driver is PIEZO1, a pressure receptor. Track with travel to altitude (lower external pressure) and the Ensure-based liquid diet works partly by reducing intestinal pressure. If you or someone you know manages IBD, the pressure dimension is worth raising with a clinician alongside diet.

• Breastfeeding duration tracks lower Crohn’s risk: The meta-analysis shows a dose-dependent protective association, strongest at the longest durations. Crohn’s is also strongly associated with a country’s degree of industrial development — close to non-existent before the modern food environment.

Personalization & supplements

• More CoQ10 is not better — there’s a dose ceiling: RCTs show ~100–200 mg/day modestly improves glucose and blood pressure, but past that the benefit reverses and markers can climb above baseline. Don’t megadose by default. The dose-response is an inverted U for most people.

• Use whole-genome sequencing over SNP chips for genetics: Masterjohn would only use whole genome sequencing for findings like COMT, not consumer SNP arrays. If you’re making decisions off genetics, the data quality of the underlying test matters more than the report.

• Reference point — Masterjohn’s own daily stack: 8 g creatine, 600 mcg molybdenum, 600 mcg K2, 100 mg CoQ10 as ubiquinol, a food-based vitamin C, plus ~100 g strawberries daily for additional vitamin C. Diet is beef and organs (liver, kidney, heart), eggs, dairy, some rice/corn tortillas/potatoes, olive oil — ~150 g net carbs, ~160 g protein. A data point, not a prescription.

Episode Blueprint

[00:00:00–00:10:00] Mitochondria as the root: ATP is the currency

Key Points

• Mitochondrial testing (Mitome) uses a cheek swab to read enzyme-complex patterns and ratios, flagging nutritional bottlenecks — e.g., a methylation-limited pattern (B vitamins, MTHFR) or a specific need for a nutrient like riboflavin or CoQ10.

• The reframe: even raising LDL receptors is an ATP-dependent process. The receptor capturing an LDL particle and moving it into the cell runs on motor proteins, chaperones, and cytoskeletal transport — all powered by ATP hydrolysis.

• ATP is a cellular currency with a variable “exchange rate,” but every active process carries an ATP cost. Mitochondrial output funds the production, maintenance, repair, and distribution of everything in the body.

• Action sits on two layers:

  • Universal basics (nutrition, exercise, sleep, sunlight, stress) that support all mitochondria

  • Idiosyncratic layer unique to your genetics, history, and current diet.

[00:10:00–00:21:00] Long time horizons, short-term miracles, and the limits of exercise knowledge

Key Points

• Optimize mitochondrial health on long horizons by default, but short-term “miracles” happen. One early Mitome customer with a CoQ10 bottleneck regained her period after 10 years of absence following targeted high-dose CoQ10.

• CoQ10 has a dose ceiling: ~100–200 mg/day helps glucose and blood pressure. Higher doses lose the benefit and can push markers above baseline.

• Our knowledge of what the average person should do for health is weakest exactly where it matters most. Elite-sport performance is well-characterized. Everyday human health optimization is not.

• Cardiorespiratory fitness is critical but likely overrated for longevity. The biggest lifespan gains cluster in sports with excellent biomechanics and joint function, not pure endurance.

Studies referenced

• Sport and longevity: an observational study of international athletes (GeroScience, 2024; Altulea et al.) — across ~95,000 athletes, male pole vaulters (+8.4 yrs) and gymnasts (+8.2 yrs) showed the largest lifespan extension while volleyball and sumo were negative; observational data.

[00:21:00–00:33:00] Biomechanics, the extracellular matrix, cancer & Crohn’s

Key Points

• Masterjohn’s brainstorm (explicitly hypothesis, not data): T-cell activation is energy-intensive and partly fueled by kinetic energy generated as the cell pushes off the extracellular matrix. Cancers can remodel that matrix to sabotage activation, so matrix quality maintained by good biomechanics may support immune surveillance.

• Population death structure runs in sequence: heart disease first, then cancer, then a diverse set of neurological/neurocognitive diseases as affluence and age advance. Larger longevity benefits imply protection drifting toward cancer and neurological disease.

• Crohn’s is reframed around pressure. The Ensure-based liquid diet rivals top biologics partly by lowering intestinal pressure. A main genetic driver is the pressure receptor PIEZO1. Flares track with travel to altitude (reduced external pressure).

• Cancer (pathologically anti-inflammatory: it evades the immune response) and Crohn’s (pathologically pro-inflammatory: it can’t resolve) are framed as opposite failures of the same pressure-and-inflammation regulation.

Studies referenced

• High altitude journeys and flights are associated with an increased risk of flares in inflammatory bowel disease patients (Journal of Crohn’s and Colitis, 2014; Vavricka et al.) — IBD patients experiencing flares had more often traveled above 2,000 m or flown within four weeks; matched case-control observational data.

[00:33:00–00:37:00] Crohn’s, development & breastfeeding

Key Points

• Crohn’s was probably near non-existent before the modern food environment. One of the strongest country-level associations is degree of industrial development, with a roughly 62-fold incidence difference cited between America and the Caribbean.

• Ecological data can’t establish individual causation but can flag what’s constant in a society — here, ultra-processed food exposure.

• Breastfeeding shows a dose-dependent inverse association with Crohn’s risk, strongest at the longest durations.

Studies referenced

• Systematic review with meta-analysis: breastfeeding and the risk of Crohn’s disease and ulcerative colitis (Alimentary Pharmacology & Therapeutics, 2017; Xu et al.) — pooled analysis found ever-breastfeeding lowered Crohn’s risk (OR 0.71), with the strongest reduction at ≥12 months duration; observational meta-analysis.

[00:37:00–00:48:00] Paleo vs. Weston Price, and the war on the word “linked”

Key Points

• Masterjohn came up paleo-adjacent but from a Weston Price lens: Price focused on what went wrong in the industrial revolution, paleo on the agricultural revolution. He locates the bigger harm in industrialization.

• His read on the agricultural transition: early populations adopted a single crop badly, hit nutrient deficiencies and stunting, then learned their way back to balance. The harm was the naïve implementation, not grain itself.

• The shared methodological obsession: the word “linked” should be purged from science because it hides both direction (did the thing go up or down?) and whether causation is being implied. An abstract should let you know the author’s view of the main findings without reading the full paper.

• The deeper problem is double-speak: researchers run studies because they want causal answers, then use vague language because they feel barred from claiming causation.

[00:48:00–00:58:00] Why peer review fails as a guardrail

Key Points

• Nutrition observational studies often use confirmatory, causal-sounding language while burying “exploratory” once or not at all — the Stanford twin (vegan) study is cited as an example of confirmatory framing.

• Peer review is described as largely theater: authors are incentivized to find a reviewer credible enough to satisfy an editor but not expert enough to mount a strong critique. Reviewers are unpaid and incentivized to do the minimum.

• Most journals don’t put a statistician on stats-heavy papers or a causal-inference expert on causal claims, so the “guardrail” depends on reviewers who often aren’t the right experts.

• Both favor transparency: single-blind review is the worst of all worlds because it lets reviewers retaliate while authors stay blind. Either fully open or double-blind would be better.

[00:58:00–01:17:00] The lipid model: oxidation, transcytosis & vitamin E as host defense

Key Points

• Feldman has long argued LDL particles don’t passively seep through healthy endothelium. The tight junctions are too tight and blood flow doesn’t favor it. Active transcytosis (notably via SR-B1) carries even unmodified LDL across — the field’s 2020 EAS consensus shift toward transcytosis is cited.

• Masterjohn agrees transcytosis matters and adds that branch points with disturbed flow and higher mechanical/shear stress are where atherosclerosis concentrates and where larger particles can cross — consistent with more endothelial damage and immune activity there.

• Both frame apoB-containing lipoproteins as part of the innate immune response. Vitamin E (alpha-tocopherol) protruding from the lipoprotein monolayer is read as host defense, not merely the particle’s own antioxidant — though Masterjohn notes vitamin E is also simply transported there.

• Familial hypercholesterolemia genetics were historically associated with lower mortality before the decline in infectious disease, supporting a quantitative trade-off: FH-range LDL is pro-heart-disease but may have been protective against infection.

[01:17:00–01:36:00] Familial hypercholesterolemia, Brown & Goldstein, and what’s really driving plaque

Key Points

• Monogenic FH carries atherosclerosis risk beyond what LDL level alone predicts (hazard ratios cited near ~2.0 for monogenic vs. ~1.3 for polygenic at matched LDL) — the steel-man counter is lifetime area-under-the-curve and in-utero exposure.

• Masterjohn’s position: the LDL-receptor impairment, not the native LDL concentration, drives atherosclerosis — by increasing particle residence time → modification → plaque.

• Feldman’s added layer: macrophages in the subendothelial space take up both modified and unmodified LDL as part of an immune response, and inflamed endothelium transcytosing more apoB lipoproteins is part of the innate-immune “dog pile.”

• Key area of friendly disagreement: whether stopping inflamed endothelium from transcytosing unmodified LDL would matter. Feldman thinks yes (part of the immune playbook); Masterjohn is more agnostic on magnitude.

[01:36:00–01:48:00] Plaque as dynamic and reversible

Key Points

• Both reject the “one-way ticket” view where a bound, modified lipoprotein simply traps a macrophage forever. By default everything is dynamic: what gets in can leave; binding affinities aren’t infinite.

• Mechanistic speculation gets a bad reputation mainly because people do it badly. Treating static diagrams as reality and forgetting basic chemistry (kinetic-energy distributions, stochastic interactions).

• Atherosclerosis is hard to study because it plays out over long horizons in a space you can’t easily film. Induced animal models often overwhelm the immune response in ways that don’t reflect everyday low-level plaque management.

• The early-20th-century animal literature found that removing the cause of atherosclerosis let lesions regress on their own — atherosclerosis as temporary and dynamic.

[01:48:00–01:57:00] The keto-CTA study and its fallout

Key Points

• The keto-CTA trial scanned lean mass hyper-responders on a ketogenic diet with very high LDL/apoB. Two headline findings: baseline plaque predicts future plaque progression. There was no meaningful association between LDL/apoB and plaque progression (R-squared near .01–.015).

• Feldman states he requested withdrawal of the paper containing the Cleerly analysis and the journal accepted, with no objection from the analysis provider — he describes the dataset as anomalous. The non-Cleerly readings (semi-quantitative, Qangio, HeartFlow) are described as still supporting the original thesis.

• More advanced statistics (minimal detectable change) imply only ~5 people in the cohort exceeded the noise floor for true progression vs. regression — consistent with a genuinely low-risk group and the reason a third (five-year) scan set is planned.

• The bigger-picture argument: even a smaller re-recruited cohort with average LDL ~240–250 should show a signal if the simplistic version of the lipid hypothesis (high LDL, high risk, every population) holds.

Studies referenced

• Plaque Begets Plaque, ApoB Does Not: Longitudinal Data From the KETO-CTA Trial (JACC: Advances, 2025; Soto-Mota, Norwitz, Feldman, Budoff et al.) — reported no association between apoB/LDL-C and noncalcified plaque progression in lean mass hyper-responders while baseline plaque predicted progression. Small single-arm longitudinal cohort. Since retracted at the authors’ request over methodological concerns affecting the data.

[01:57:00–02:16:00] Seed oils: the mechanism and the only two long trials

Key Points

• The core problem with seed oils is that polyunsaturated fats are an oxidative liability, more vulnerable to peroxidation than any other macronutrient, rather than an acute toxin. The damage shows up as membranes and lipoproteins become more oxidizable and aging supplies the oxidative stress.

• The vulnerable site is the bis-allylic carbon between two double bonds, which is why PUFAs (not MUFAs) carry the risk. Essential PUFAs are needed in small amounts. The liability is chronic high intake.

• Short trials (8–12 weeks) show seed oils improving liver fat and metabolic control. Multi-year trials trend neutral-to-harmful for heart disease and increased for cancer. In nutrition, short-term benefit reversing over the long term is a recurring pattern (the SSRI-discontinuation difficulty over years is offered as a parallel).

• The mechanistic trade-off even by the conventional lipid hypothesis: PUFAs lower liver fat and raise LDL-receptor activity, but enrich the LDL particle with exactly the fats that oxidize and seed plaque — a genuine double-edged sword, which is why long trials matter.

Studies referenced

• A Controlled Clinical Trial of a Diet High in Unsaturated Fat in Preventing Complications of Atherosclerosis (LA Veterans Administration Trial) (Circulation, 1969; Dayton et al.) — a multi-year double-blind RCT where the high-PUFA group showed no mortality benefit and higher cancer incidence; one of only two long, large, blinded seed-oil trials.

• Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73) (BMJ, 2016; Ramsden et al.) — recovered-data reanalysis of a double-blind RCT showing linoleic acid lowered cholesterol ~13.8% but produced no mortality benefit and higher death per unit of cholesterol reduction; the second of the two long blinded trials.

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[02:16:00–02:34:00] PUFA membrane loading, trial design & regression to the mean

Key Points

• Diet can shift the fatty-acid composition of membranes, expanding the PUFA slice of the phospholipid “pie chart,” but the change is slow (years) and tissue-dependent — biggest in adipose triglyceride, more modest elsewhere, tightly regulated in the brain.

• A hidden harm of chronic seed-oil intake: vitamin E gets diverted into expanding adipose stores, leaving less available to protect other tissues like skin.

• Trials stopped early for benefit exploit regression to the mean — a dramatic early result is more likely luck than a durable effect. Stopping locks in the favorable snapshot. Masterjohn frames this as the same statistical principle behind “tall fathers have shorter sons.”

• The longest seed-oil trial (LA Veterans, ~8 years) concluded its own duration was too short, since cancer incidence in the seed-oil group climbed most in years 5–7. The field then mostly produced 7–12 week trials.

[02:34:00–02:54:00] Research integrity, transparency & decentralized science

Key Points

• Most research is described as a waste because scientists chase fundable, low-disruption questions rather than the most important knowledge gaps — “dancing around the edge” of existing recommendations to avoid rocking the funding boat.

• Large trials are effectively never replicated given their cost, which raises the stakes on the objectivity and quality control of whoever runs and measures them.

• Feldman’s stated path forward: decentralized, crowdfunded science with open code and open data, releasing everything so anyone (now aided by AI) can re-run analyses and surface errors quickly — how he says problems in the keto-CTA data were caught within 24 hours.

• Political inertia around NIH funding is described as severe enough that meaningful reallocation would require Congress, which is partly why the open/crowdfunded route may move faster.

[02:54:00–03:00:00] Listener Q&A: defining food, diet & supplements

Key Points

• On defining “food”: Masterjohn treats it simply as something edible and rejects equating “food” with “what I should eat” — there are foods you shouldn’t eat. Echoes Gary Taubes’ “food vs. food-like substances.”

• His diet: beef and organs (liver, kidney, heart), 4–5 egg yolks/day, dairy including ~150 g heavy cream, some rice, corn tortillas, potatoes, vegetables, olive oil — ~150 g net carbs, ~160 g protein, ~2,800 kcal/day, all weighed out.

• Supplements: 8 g creatine, 600 mcg molybdenum, 600 mcg K2, 100 mg CoQ10 as ubiquinol, a food-based vitamin C, plus ~100 g strawberries/day for additional vitamin C.

• On genetics: use whole-genome sequencing, not SNP chips, for findings like COMT.

Listen & Watch

• YouTube

• Spotify

• Apple Podcasts

• Where to find Chris Masterjohn:

  • Here on Substack: Harnessing the Power of Nutrients ()

  • Mitochondrial testing: mito.me

  • On X

• Where to find Dave Feldman:

  • On X

  • On YouTube

  • Website: feldmanprotocol.com

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As promised, a dense one. But well worth at least the cursory understanding as these two gents are about as leading edge in the mitochondrial health space as they come.

Your friend,
Phys

80%+ of the time it’s feasible to hit a whole foods, home cooked meal. But in that 20% of the time it’s not, I prefer something quick without the compromise.

Each time I post what falls into that convenience bucket, the esoteric health bros come at my neck with “just eat real food”. Inevitable.

What these same dudes fail to take into account is most of us have lives we adapt to. We don’t shape them around a neurotically organized eating schedule. I’m not packing a Tomahawk steak in my gym bag when I’ve got somewhere to be/not heading home after a training session.

But lucky for us, it’s 2026 and there’s no excuse for not getting clean nutrition on the go.

V1 Nulla was good. I don’t like changing things up if they’re working. So I kept going back to the well. That was until Marc at CleanForm assured me these were in a league of their own. I was a bit skeptical at first, which I’ll explain later.

Let’s jump into what the V2 Nullas are all about.

What’s actually in it

Metabolic health is a priority here. That means we wouldn’t even bother discussing a product if it didn’t meet our clean ingredient profile standard.

A lot of protein bars are now shifting towards this nutritional gymnastics to keep protein content high with as minimal calories as possible. What that usually means is being deceptive about the actual calorie content (see: recent David protein bar controversy)

What you see is what you get with the V2 just like the V1.

Ingredient breakdown:

• Almond Butter (Almonds)

• Honey

• Allulose

• Milk Protein Isolate

• Whey Protein Isolate

• Dark Chocolate (Chocolate, Sugar, Cocoa Butter, Soy Lecithin (Emulsifier), Vanilla)

• Whey Crisp (Whey Protein Concentrate, Rice Flour)

• Vegetable Glycerin

• Monk Fruit

• Imitation Vanilla Flavoring (Water, Sugar, Alcohol, Vanilla Extract, Caramel Color, Vanillin)

• Sodium Beta-Hydroxybutyrate (as goBHB®)

Nutrition Facts (per 1 bar / 68g serving)

• Calories: 260

• Total Fat: 11g (14% DV)

• Saturated Fat: 2g (10% DV)

• Trans Fat: 0g

• Cholesterol: 5mg (2% DV)

• Sodium: 15mg (1% DV)

• Total Carbohydrates: 28g (10% DV)

• Dietary Fiber: 3g (11% DV)

• Total Sugars: 15g

  • Includes 12g Added Sugars (24% DV)

• Protein: 20g

• Vitamin D: 0%

• Calcium: 20%

• Iron: 4%

• Potassium: 4%

What I’m liking most about both versions is what they decided to leave out.

No seed oils. No filler ingredients. No gluten.

Look closely enough at most mainstream bars and they’re stacked with omega-6 oils as the default fat. From a margins standpoint, it makes sense – they’re cheaper & more shelf-stable. From a health of the customer perspective – not so much.

A quality off-the-shelf product in 2026 is defined less by what’s in it and more by what isn’t. CleanForm again has shown they get that.

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What’s different from V1

Not just a new flavor & taste profile. A couple new ingredients set the V2 apart: honey & goBHB.

They’re not just dumping high fructose corn syrup or even cane sugar in there to sweeten the flavor profile. It’s real honey. And if it’s one thing you shouldn’t fall for here, it’s the dietary reductionism of “muh liquid sugar”. Honey is nature’s sweet medicinal elixir.

The other piece added is the goBHB — a patented, exogenous ketone supplement made from beta-hydroxybutyrate (BHB) salt. A nice addition for appetite suppression & the natural energy feel, but a supplement that I haven’t been totally sold on yet. Plus the ~1g isn’t close on the 8—10g+ clinically-tested dosing. Point being, I’m not buying these for the BHB.

How they actually taste

If I can sum it up quickly: cookie dough crisp.

These came in a few weeks ago…just as I was ~3 weeks into my current 10 week cut. If this is you, just buy one of those cell phone lock boxes before you get a box of these. You’ll take one down and want six more.

They’re dangerously good. I’ll put it into perspective: Lady Phys despises the typical protein bar – Quest, Pure Protein, Kirkland…the list goes on (cottage cheese is her primary source…IYKYK). Her initial reaction: “I feel like I’m eating straight cookie dough. Get these away from me before I eat the box.”

But the real standout piece of V2 is the texture. You’ll immediately be blown away by the crisp on the first bite.

Overall, the flavor profile & texture is incomparable to any bar I’ve ever tried. And I’ve tried my fair share over the last couple decades.

Yes – think back to the PowerBar days…and every bar since then. Those who know, you can practically taste the font.

How I’ve been eating them

Just like the V1 Nullas, these are best coming out of the fridge. Even better crumbled over a Creami as a topping.

Beyond that, they do exactly what a convenience food should. These are excellent for travel or a fast 20g protein bolus post-training when going home to cook isn’t in the cards.

Verdict

These are a clear add to my rotation. They hit every wicket I care about on the protein-snack front:

• Strong protein-to-calorie ratio: 20g protein at 260 calories. No goofy macro 4D chess to get there.

• Clean ingredient profile: No seed oils, no filler, no gluten.

• Texture and taste like you’ve never had in a “protein bar”: the crisp…oh man the cookie dough crisp.

• Fair price: especially for a brand-new DTC entrant in a brutally competitive category.

• Portable: this is the entire point, of course.

Where to Buy

Grab a pack of 12 for $36 with code PHYS10 at checkout.

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Enjoy, friends. And I hope you guys love ‘em as much as I do.

Until next week. Stay after it.

Your friend,
Phys

The Phys Debrief · #01
The practical takeaways & latest research from the health space's most valuable long-form content, without the rest.

Peptides have officially become a household term.

It was only a matter of time before the biggest names in the health game caught on. And who better to welcome the topic into the mainstream peptide era than the most based doctor on this side of the health space:

Given our immense respect for Abud, we’re kicking off The Phys Debrief series immortalizing his most recent & wildly popular podcast appearance.

Side note: You can manifest things. You can just speak them right into existence. A month-old prediction coming true.

Full episode linked below for your next Zone 2/3 session.

Contents:

• In 1 Sentence

• In 50 Words

• In 250 Words

• Practical Takeaways

• Episode Blueprint

• Where to Listen & Watch

Share

In One Sentence

The most useful way to think about today’s peptide boom is to ask whether a given peptide has a known receptor — GLP-1s do and work predictably, while most everything else (like BPC-157, Russian bioregulators, thymic peptides, GHK-Cu) is promising but rests on animal models, single-lab data, and anecdote, which implies lifestyle fundamentals and clean, physician-monitored sourcing matter more than the molecule itself.

In 50 Words

Peptides are exploding in popularity and poorly understood. Bakri’s lens: known-receptor peptides (GLP-1s) are strong and predictable; no-receptor peptides (BPC-157, bioregulators, thymic peptides, GHK-Cu) are promising but thinly evidenced in humans. Most people buy from an unverified gray market. Foundations first. Physician oversight and reputable sourcing are paramount.

In 250 Words

Bakri’s organizing framework is one question: does a peptide have a known receptor? GLP-1s do, so their effects are strong and consistent. BPC-157, TB-500, and the Soviet-era “bioregulators” don’t (or we haven’t found them…yet), so they likely act by modifying existing proteins or as epigenetic modifiers. And their human evidence is thin.

BPC-157 is the centerpiece. Discovered from gastric juice by one Croatian group (Sikirić’s lab), its impressive healing data is almost entirely animal. It appears to accelerate repair by upregulating angiogenesis, nitric-oxide signaling, and growth-factor activity, which is also why a theoretical cancer concern exists (it could feed an existing tumor). Oral BPC doesn’t seem to reach the bloodstream, but injectable does. Bakri thinks the underexplored gut and neuro effects (gut protection, blunted addiction/stimulant reward) are more interesting than the musculoskeletal hype.

The bioregulators (pinealon, epitalon, vilon) act like transcription-assisting epigenetic modifiers. Huberman reports pinealon dramatically raising his REM fraction. The thymus shrinks from puberty and its decline tracks cancer/autoimmune/cardiovascular risk. A $3 lymphocyte-to-monocyte ratio is a usable proxy almost no clinician checks. GH secretagogues raise your own IGF-1 but worsen insulin sensitivity. GLP-1s are the one category with robust receptor-based human data and are reshaping metabolic medicine.

Nearly all peptide Active Pharmaceutical Ingredients (API) is Chinese and splits into big-pharma, compounding, gray-market, and black-market tiers of wildly varying quality → Wild Wild Peptide West. Get the foundations right first. If you proceed, do it with a peptide-literate physician, objective endpoints, and verified sourcing.

Practical Takeaways

Mental Models (first principles)

• Sort any peptide by one question: Does it have a known receptor? Receptor peptides (GLP-1s) produce strong, predictable effects. No-receptor peptides (BPC-157, TB-500, bioregulators) may act via protein modification or epigenetics, but their human effects are largely unproven. As a shortcut, a drug name ending in “-tide” signals a peptide and the root often hints at the mechanism.

• Foundations are the floor & peptides are additive on top: AM sunlight, consistent sleep, minimally processed food, and regular training come first. Bakri is explicit: stacking peptides is pointless if the basics aren’t in place.

BPC-157

• Calibrate your confidence to the data: Almost all efficacy and safety data is animal and comes from a single Croatian group. Meaningful human data amounts to roughly one small ulcerative-colitis trial. The most-cited “proof” (an Olympic athlete’s Achilles recovery) is hearsay.

• Mechanism is pro-repair, not anti-inflammatory: It appears to upregulate VEGF/angiogenesis, nitric-oxide signaling, growth-factor receptor density, and cell migration (especially stacked with TB-500). The same angiogenesis is the basis of the theoretical tumor-vascularization concern, which is exactly why Huberman won’t take it when he isn’t injured.

• Route matters: Oral and rectal BPC don’t appear to reach systemic circulation (not detected in blood); injectable does. Most people inject ~100–250 mcg, but Bakri argues the effective human dose is probably far higher. Dosing is guesswork because there’s no human pharmacokinetic data.

• The under-discussed effects are gut and neurological: Gut protection (anti-ulcer, anecdotal travel/GI resilience), plus a homeostatic dampening that in animals blunts intoxication and withdrawal — and in some users blunts stimulant/addiction reward (reported “blunted Adderall,” low mood/anhedonia).

• “PDA” is BPC-157: Compounded “pentadecapeptide arginate” is the same molecule in a different salt. The current legal workaround as FDA compounding status shifts.

Bioregulators (pinealon / epitalon)

• The naming is backwards: Pinealon (tripeptide EDR) comes from cortex extract, not the pineal. Epitalon (AEDG) is the pineal one. Both behave like transcription-assisting epigenetic modifiers with no known receptor.

• Timing flips pinealon’s effect: Morning or pre-workout, it’s an anti-fatigue/cognitive tool. High doses near bedtime can fragment deep sleep. Huberman’s anecdote: a small dose taken on a mid-night waking sharply increased his REM fraction with lingering benefit on subsequent nights.

• Watch blood sugar and expect vivid dreams: Pinealon modulates metabolic and antioxidant pathways (PPAR-α/γ, SOD, GDF11, irisin). Some users see blood glucose (& HbA1c) drop. Use extra caution if hypoglycemia-prone. Intense, unusually vivid dreams are common.

• Epitalon is interesting because it targets repair machinery, not a downstream receptor: Animal data span retinal degeneration (retinitis pigmentosa, glaucoma models) and restoration of melatonin rhythm in aged animals.

The peptide space has become the Wild Wild West of the health world.

In a category this unregulated, inside a health movement getting more decentralized by the day, I refuse to gamble on anything less than the highest-quality tools.

That’s why I’ve been using YourProtocol. Every batch is 3rd-party lab tested for purity and made in an FDA-registered, GMP-certified facility. They’ve built their reputation on proof and became my only source for oral BPC and bioregulators.

• Restore BPC: what I used to heal my gut lining last year.

• PinealON: for clear, focused cognition when the stress load piles up.

• EpitalON: for deeper sleep and the long game on recovery and longevity.

Don’t take my word for it. Check the lab tests and reviews yourself.

Pick up your protocol (& use PHYS10 at checkout for 10% off your next order).

Pick Up Your Protocol Here

Thymus & Immunity

• The thymus is a longevity-relevant organ, not vestigial: It shrinks from puberty (driven by sex hormones and corticosteroids), and its decline tracks rising cancer, autoimmune, and cardiovascular risk. Removing residual thymus during cardiac surgery carries a measurable mortality signal.

• Use the cheapest immune-aging proxy you already have: The lymphocyte-to-monocyte ratio from a standard CBC with differential (~$3) tracks outcomes across many diseases. Aim for robust lymphocytes (~1,500–3,000) with low monocytes. Almost no clinician looks at it.

• Know the thymic peptides apart: Thymosin α1 is pro-immune (Bakri self-experiments with ~2.5 mg twice weekly as travel/hospital prophylaxis — not an approved use). TB-500 is a synthetic Thymosin β4 fragment (and a known doping agent, especially equine). Thymalin (Russian peptide mixture) is not Thymulin (the French zinc-dependent nonapeptide). Thymulin requires adequate zinc; falling thymulin is the earliest marker of zinc depletion.

GHK-Cu

• Strongest evidence is topical for skin: This copper tripeptide (Gly-His-Lys) sits in type-1 collagen, is high in youth, and both builds and remodels collagen. Topical human data on photoaging is reasonable (roughly comparable to retinol/vitamin C). Hair data is weak as it’s not a minoxidil replacement and at best an adjunct.

• Use it with a routine and pair with red light: GHK-Cu and red-light therapy appear synergistic for collagen/photoaging. A legitimate product should be blue (from the copper). Don’t inject it into your face.

Growth Hormone Secretagogues

• These raise your own GH/IGF-1 rather than injecting GH: GHRH-type (sermorelin, tesamorelin) vs. ghrelin/GHRP-type (ipamorelin, MK-677). MK-677 drives large, non-pulsatile GH and the most appetite and side effects. Tesamorelin + ipamorelin can push IGF-1 to puberty-range levels.

• There are trade-offs: GH and secretagogues worsen insulin sensitivity (A1c rises). The bodybuilding maxim is “get lean enough to run GH”. The open question is promotion of an existing cancer, not initiation. Huberman tried sermorelin: it boosted deep sleep, suppressed REM, and spiked his PSA — he stopped immediately.

GLP-1s

• This is the one category with strong, receptor-based human data: It’s reshaping metabolic medicine (10–30% body-weight loss). The class originated from Gila-monster peptide. Retatrutide (a GLP-1/GIP/glucagon triple agonist) is the next wave.

• Titrate slowly and pair with lifestyle (”training wheels”): Many reported negatives (like low mood, fatigue) track with under-eating, low electrolytes/protein, and crashed blood sugar from mega-dosing, not necessarily the drug itself. Bakri’s own 1 mg cold-start produced a night of projectile vomiting. Don’t cold-start high.

• Mind the second-order effects: Microdosing under monitoring at the lowest effective dose is the sane approach. Fertility can rebound as obese/anovulatory women lose weight and leptin normalizes (”Ozempic babies”). GLP-1s are not contraception.

Sourcing & safety

• Understand the supply chain: Nearly all peptide API is Chinese. It then splits into big-pharma (most stringent), compounding pharmacies (variable), gray-market “research use only” (unknown identity, dose, and batch-to-batch consistency), and black market (avoid entirely). Gray market is how most people actually buy.

• Ask your prescriber the markup question: Ask what the compounding pharmacy charges them vs. what they’re charging you. The spread often goes to the clinician, a practice of dubious legality. And no malpractice carrier covers non-FDA-approved injectable peptides.

• If you proceed, do it right: A peptide-literate physician, objective monitoring (e.g., IGF-1 on secretagogues), and verified sourcing. The likely near-term future is physician-led telehealth that drives prices down and surfaces which compounders are reliable.

Subscribe now

Episode Blueprint

[00:00:00–00:06:26] Introduction & What Peptides Are

Key Points

• Huberman frames the “celebrity protocol”: stacking a GLP-1, a GH modulator, and androgen therapy to transform body composition fast as the cultural backdrop.

• Bakri’s core taxonomy: peptides are a cellular communication “language” sitting between steroid hormones and full proteins. The key split is known-receptor vs. no-receptor.

• GLP-1s have clear receptors (strong, consistent effects). BPC-157 and TB-500 have no identified receptor.

[00:06:26–00:19:27] BPC-157: Discovery, Mechanism & Neuro/Gut Effects

Key Points

• Origin story: Pavlov’s gastric-juice work + Hans Selye’s stress-damage observations led a Croatian group (1991) to isolate the 15-amino-acid BPC-157 from a larger gastric protein. We don’t natively make BPC-157. We make the parent protein.

• Animal work: faster healing of severed tendons/ACL, protection against burn-induced gastric ulcers. The Achilles paper is what ignited athlete interest.

• Proposed mechanism is pro-repair: VEGF/angiogenesis, nitric-oxide signaling, more growth-factor receptors, cell migration and it preserves healing even alongside corticosteroids.

• Bakri finds the neuro/gut effects more compelling than musculoskeletal: animals get “less drunk,” withdraw less severely, and some users report blunted stimulant reward via the gut-brain axis.

Studies referenced

• A new gastric juice peptide, BPC (Journal of Physiology-Paris, 1993) — Frames BPC as a gastric-juice peptide that protects organs against stress-induced damage; the conceptual root of BPC-157 (Sikirić group).

• BPC 157 accelerates healing of transected rat Achilles tendon (Journal of Orthopaedic Research, 2003) — In rats and tendon-cell culture, BPC-157 sped healing of a fully severed Achilles tendon; the result that drove athlete interest.

• Achilles detachment in rat and BPC 157: tendon-to-bone healing, opposed corticosteroid aggravation (Journal of Orthopaedic Research, 2006) — BPC-157 improved tendon-to-bone healing and counteracted corticosteroid-impaired healing; basis for the “pro-repair, not anti-inflammatory” claim.

[00:19:27–00:29:41] BPC-157: Adverse Events, Trials & Legality

Key Points

• No known LD50 (animals tolerated ~1,000× doses), which itself blocks FDA approval.

• Human data ≈ small phase 1/2 rectal-enema trials for ulcerative colitis (~80 mg) from the same Croatian group (abstracts only, full data unavailable). Orally/rectally administered BPC wasn’t detectable in blood.

• Legality is shifting and state-dependent: BPC-157 was never FDA-approved → moved to a “do-not-compound” list in late 2024 → then off it in 2025. Compounded “PDA” is the workaround. Telehealth law follows the patient’s state.

[00:29:41–00:41:32] The Peptide Market: Compounding, Gray & Black Market

Key Points

• The GLP-1 shortage pushed people to compounding pharmacies and gray-market “research only” sites. Injecting became normalized, which de-stigmatized peptides broadly.

• Nearly all API is Chinese. Quality runs from excellent to dreadful, batch to batch, with no way for the buyer to verify.

• More than half the peptide market is women (GHK-Cu, skin/collagen). Affiliate selling exploded.

[00:41:32–00:54:19] Tumor/Angiogenesis Risk; Patents & Designing a Real Trial

Key Points

• The honest worry: BPC-157’s angiogenesis could vascularize an undetected tumor. No human signal exists, but there’s also no good human data and in some models it actually decreased VEGF (e.g., a melanoma line).

• Patents are weak (add one amino acid and it’s a “new” compound). The original patent passed to Teva, which has no incentive to develop it.

• A sensible trial program: finish the colitis work (encapsulated, not enema), test GERD vs. pantoprazole, and study tendon-repair endpoints (e.g., post-surgical bicep/ACL recovery time).

[00:54:19–01:07:25] BPC-157 Anecdotes; Physician, FDA & Malpractice

Key Points

• Bakri’s grade-2 tricep tear (normally ~3-month recovery) healed in 3–4 weeks with local high-dose injection plus other peptides. Huberman’s acute neck/trap pull resolved in 2 days after ~200 mcg. Both stress these are uncontrolled anecdotes.

• Dosing online is set by “what fits in the vial,” not data.

• Patients can sue the physician, the pharmacy, and the recommender. No malpractice carrier covers non-FDA-approved injectables. The right model is a frank physician-patient discussion with monitoring and clear endpoints.

[01:07:25–01:29:38] Bioregulators: Pinealon/EDR & Epitalon

Key Points

• Pinealon (EDR) derives from cortex extract. Epitalon (AEDG) from the pineal — the names mislead. Both act like epigenetic modifiers that help expose promoter regions of DNA.

• Pinealon improves daytime cognition/anti-fatigue (Khavinson’s athlete studies) and raises REM fraction with lingering effects. Watch for blood-sugar drops and vivid dreams.

• Epitalon targets DNA-repair machinery relevant to retinal degeneration and melatonin-rhythm restoration. Khavinson’s framing: replenishing youthful peptides that decline with age, with benefits that accrue even when off-cycle.

Studies referenced

• Pinealon increases cell viability by suppressing free radicals and activating proliferation (Rejuvenation Research, 2011) — In neuronal/cell models, pinealon raised viability by lowering free-radical levels. Mechanistic support for the “better oxidative state” story, not human sleep data.

[01:29:38–01:50:33] Thymus, Thymosin α1, TB-500, Thymulin & Pets

Key Points

• The thymus shrinks from puberty under sex hormones and corticosteroids. Lower thymic function tracks worse outcomes across diseases. Fahy’s TRIIM trial regrew it with GH + metformin + DHEA.

• Thymosin α1 (pro-immune; FDA-approved abroad/for congenital athymia as Zadaxin) used by Bakri as travel prophylaxis. TB-500 = Thymosin β4 fragment (actin/cell migration; equine doping agent).

• Thymalin (Russian peptide mix) ≠ Thymulin (French zinc-dependent nonapeptide that augments end-organ hormone responses and requires adequate zinc).

• Veterinary openness to peptides is high. A large “pet peptide” market is emerging.

Studies referenced

• Health consequences of thymus removal in adults (New England Journal of Medicine, 2023) — Adults who had the thymus removed showed higher all-cause mortality and cancer risk; the residual adult thymus still matters.

• Thymic health consequences in adults (Nature, 2026) — In a human MRI cohort, higher thymic scores tracked lower cardiovascular and cancer mortality; supports thymic function as a measurable longevity metric.

• Reversal of epigenetic aging and immunosenescent trends in humans (TRIIM trial) (Aging Cell, 2019; Fahy et al.) — A 12-month GH + metformin + DHEA cocktail regrew thymic tissue and reversed epigenetic-age estimates; proof-of-concept, small and uncontrolled.

• Chemical characterization of thymosin β4 (Journal of Biological Chemistry; Goldstein lab) — Characterized the thymosin β4 peptide, the parent of TB-500.

• Human whole-blood NAD+ levels do not vary with age or lifestyle interventions (Nature Metabolism, 2026) — Whole-blood NAD+ didn’t decline with age or shift with lifestyle interventions. Complicates the “boost NAD for longevity” narrative behind NMN/NR (raised in the same tangent).

[01:50:33–02:04:01] GHK-Cu & a $3 Immune-Aging Blood Test

Key Points

• GHK-Cu (Gly-His-Lys + copper) sits in type-1 collagen, declines with age, and both synthesizes and remodels collagen. Discovered by Loren Pickart. Topical skin data is reasonable, but the hair data is weak.

• Illness recovery: every infection causes transient thymic atrophy. Chronic stress prevents rebound, leaving people repeatedly sick.

• Practical tool: the lymphocyte-to-monocyte ratio on a routine CBC is a cheap, ignored proxy for immune robustness and disease risk.

Studies referenced

• Protective effects of GHK-Cu in bleomycin-induced pulmonary fibrosis (Life Sciences, 2020) — In an animal fibrosis model, GHK-Cu reduced fibrosis via anti-oxidative/anti-inflammatory pathways; basis for emerging (preclinical) interest in lung/COPD/long-COVID regeneration.

[02:04:01–02:15:36] Growth Hormone Secretagogues

Key Points

• Secretagogues raise endogenous GH/IGF-1: GHRH-type (sermorelin, tesamorelin) vs. ghrelin/GHRP-type (ipamorelin, MK-677). MK-677 produces the largest non-pulsatile GH and most side effects.

• Somatopause (GH decline in the 30s) is the target; the debate is whether replacing it helps or harms longevity (GH-deficient models often live longer; antagonistic pleiotropy).

• GH worsens insulin sensitivity and may promote existing tumors; Huberman’s sermorelin trial spiked his PSA and suppressed REM.

[02:15:36–02:20:25] GHK-Cu Topical + Red Light

Key Points

• Best results: a well-formulated topical (should be blue) used alongside a normal skincare routine, not instead of it.

• GHK-Cu and red/near-IR light appear synergistic for collagen and photoaging. Sunlight is the original full-spectrum source.

Studies referenced

• Longer wavelengths in sunlight pass through the body and improve vision (Scientific Reports, 2025) — Red/near-IR wavelengths penetrate the body and exert systemic effects, including on vision. Context for the GHK-Cu + red-light synergy and “sunlight is the best source.”

[02:20:25–02:39:03] GLP-1s & Retatrutide

Key Points

• The class (from Gila-monster peptide) is transforming metabolic medicine; without it the system would buckle under obesity/diabetes. Robust receptor-based human data sets it apart.

• Long-term/cognitive effects of thousand-fold GLP elevations are unknown. Reported mood/energy issues often trace to under-eating and electrolyte/blood-sugar problems rather than the drug.

• Retatrutide (39 amino acids) is being positioned as a biologic (longer patent protection, harder to compound). Nomenclature is a mess — “peptide” is too broad to be a useful category (carnosine and retatrutide are both peptides).

Studies referenced

• Early onset of reproductive function in female mice treated with leptin (Science, 1997; Chehab et al.) — Leptin accelerated onset of reproductive function in female mice. Mechanistic backdrop for the fertility rebound (”Ozempic babies”) as body fat and leptin normalize.

[02:39:03–02:48:00] Women’s Reproductive Disorders, TBI & Safe Sourcing

Key Points

• No animal or human data supports BPC-157 or similar for endometriosis/fibroids. Those are hormonal/metabolic problems where the hormonal lever is far stronger.

• TBI: Russian work on cortexin and cerebrolysin exists but won’t be US-available. BPC’s neuro effects are homeostatic (”won’t let the brain go too far in either direction”).

• Where to get peptides safely: not gray-market sites; build a relationship with a peptide-literate physician, monitor objective endpoints, and expect physician-led telehealth to improve sourcing and price over 6–24 months.

Listen & Watch (on 0.75x speed…IYKYK)

• YouTube:

• Spotify:

• Where to find Dr. Bakri:

  • Here on Substack:

  • On X

  • On Instagram

Pair this together with our peptide history timeline & you place yourself in the top 1% of knowledge in this space.

Downloadable PDF plot below for detailed viewing (abridged version):

Peptide Hype Cycle

525KB ∙ PDF file

Download

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And we’ll be talking a lot more about these in the near future.

Stay after it until then.

Your friend,
Phys

If your great-grandfather were alive today, he’d be horrified at the thought of his 25 yr-old self being plagued by a disease of the elderly.

Now we’re in the midst of a silent epidemic.

It’s the single most common issue men in their 20s and 30s ask me about — they can’t get it up. Or they can, but their drive sucks. Morning wood vanishes. Vitality lost. Sex embarrassingly bad.

It’s the same story over & over again:

1. Can’t get it up.

2. Take the PDE5 inhibitor (tadalafil or sildenafil).

3. All is well.

4. Come off.

5. Limp again.

Just anecdotal?

Nope.

More than HALF of all guys under 35 are experiencing erectile dysfunction, while 75% suffer in silence.

One pediatric urology practice just found a 31x increase in teenage males with ED since 2014.

Still not buying it? Then follow the money and it’ll make more sense: the ED drug market already clears $3 billion a year and is projected to double by 2033.

Here’s the good news: ~90% of cases are reversible when you address the root causes early enough. And the sooner you address them, the better. Upstream damage that’s easy to reverse at 25 becomes a decade of dysfunction by 35.

But we’ve been having the wrong conversation.

For the past decade, the health space has offered a single villain: “It’s the porn!” It’s repeated ad nauseam and nothing has changed (situation has only worsened).

The explanation isn’t wrong. It’s just reductionist, incomplete, and frankly lazy. We build strategies here. We don’t hunt tactics.

So it’s time to go upstream. To the 5 systems & 15 causal factors actually driving the modern flaccidity epidemic.

System 1: Vascular Engine

Factor #1 — Cardiometabolic dysfunction

How

• Body fat past ~20% kills erection quality: Excess visceral fat is a cocktail of aromatase + poor mitochondrial function + inflammation + leptin/insulin resistance.

• Combined high-fat & high-carb breaks metabolic flexibility: Hyperpalatable foods (highly processed) impairs glucose oxidation. Clean carb oxidation generates the CO₂ driving vasodilation & libido.

• Metabolic slowdown makes a low-energy state: Low thyroid. Low gut short-chained fatty acids (SCFAs). Elevated chronic stress hormones. Micronutrient scarcity.

• ED² (Endothelial Dysfunction = Erectile Dysfunction): Leptin/insulin resistance, low-grade chronic inflammation, & oxidative stress suppress NO signaling in the tiny helicine arteries of the penis well before the coronaries. It’s why ED is the earliest canary in the CVD coal mine.

Evidence

A 2025 analysis found metabolic disease raised ED odds 2.3x.

Molina-Vega et al. (2019) reported 42% ED prevalence in non-diabetic obese men.

In 193 young men with early coronary disease, ED prevalence was 57.8% vs. 31.1% in controls.

Fix

• Track cardiometabolic health biomarkers: See below.

• Build your aerobic engine (most validated non-drug ED fix): A 2023 RCT meta-analysis improved erectile function 2.3–4.9 points. Base building with 60+ min daily of low-level aerobic movement (walks) & 2–4 focused sessions (1–2 HIIT & 1–2 moderate intensity).

• Build muscle as a glucose sink: Lift 3–4x/week. Clears glucose & improves androgen signaling.

• Fix fuel partitioning: Favor clean carbs (potatoes + rice + fruit) without added fats. Avoid high-fat + high-carb combos that drive insulin resistance. Warm hands/feet, no post-meal crashes, & morning wood are solid biofeedback forms.

• Drop to ~12–15% body fat: Strips the aromatase converting your testosterone to estrogen.

• Support the mitochondrial cofactors/substrates: B-vitamins. Creatine. Magnesium. Ubiquinol (preferred CoQ10 source). Taurine. PQQ. K2. Zinc/copper (balanced to ~10:1).

• Hold off on TRT: Lose the visceral fat first. Then weigh the decision. A 2014 RCT found it didn’t fix insulin resistance or visceral adiposity.

Factor #2 — Redox imbalance

How

• Modern stress bottlenecks the electron transport chain: Concentrated blue light. nnEMF. High Omega-6/Omega-3 loads. Mouth breathing. Endotoxin. Nutrient gaps. Electrons leak → reactive oxygen species spike → depletes glutathione (master antioxidant) → NADH backs up (reductive stress) → lactate increases.

• Stressed mitochondria deprioritize sex steroids: Cholesterol reroutes toward cortisol in what is known as the pregnenolone steal & androgen receptors get sequestered. Total T levels usually will read as normal (deceptively).

• Imbalanced GABA/glutamate drives excitation: Glutamate & Ca²⁺ influx (cortisol, adrenaline, blue light, nnEMF) collapse mitochondrial membrane potential and spike ROS.

• Low T3 starves the system: Weak thyroid impairs mitochondrial biogenesis & ATP production further tanking steroidogenesis & Leydig responsiveness to LH.

Evidence

Xu et al. (2024) found that better oxidative balance scores built from 16 dietary and 4 lifestyle components tracked with lower ED risk.

Fix

• Rebuild ETC cofactors: Thiamine (B1). All B-vitamins (B2/B3/B5/P5P/B9/B12). Ubiquinol. Taurine. Magnesium. Balanced copper/zinc & selenium/iodine. Adequate saturated fat.

• Load testicular antioxidants to protect sperm from peroxidation: NAC. Taurine. Tyrosine. Vitamin E + C. Ubiquinol. L-carnitine. Selenium. Ginger. Creatine. to protect Leydig cells and .

• Eliminate oxidative inputs: Seed-oil PUFA. Alcohol. Hyperpalatable processed foods.

• Support glucose oxidation & thyroid: Carbs timed with light (breakfast w/ sunrise & lunch w/ UV-B midday sun). Avoid high Omega-6 & estrogenic toxins. Supplement T3 if needed.

• Deploy targeted libido tools: Low-dose tadalafil (5 mg). Tribulus. Black ginger. Capsaicin-based foods. Agmatine sulfate. Red/IR on the balls. Brief cold exposure.

• Clear the upstream stressors first: Fix gut/endotoxin (#4). Lower prolactin/serotonin excess. Balance pregnenolone/progesterone (#11).

Factor #3 — Micronutrient depletion

How

• Sad story of SAD: Standard American Diet is one of micronutrient insufficiency (undernourished) & caloric excess (overfed).

• Modern depletion outpaces intake: Soil depletion. Processed/plant-heavy diets. Hydrogenated vegetable oils. Gut dysbiosis. All cut absorption and raise demand for the cofactors Leydig cells need for cholesterol side-chain cleavage and steroidogenesis (zinc, copper, magnesium, retinol, B-vitamins, selenium, electrolytes).

• Zinc depletes first: The cofactor for testosterone synthesis, LH signaling, and aromatase control. Drains from tissues for years before labs reflect. Then low T, high estrogen, wrecked sperm count/motility/morphology, weak libido.

• Copper collapses on unbalanced zinc: Cytochrome c oxidase loses efficiency, dopamine synthesis falls (tyrosine hydroxylase), thyroid conversion stalls, and iron gets trapped. All starve gonadal energy & NO production.

• Magnesium burns under high stress, excess blue light, & nnEMF: SHBG rises (locking up free T), vascular smooth muscle can’t relax, and mitochondrial ATP decreases.

• Fat-soluble vitamins fail without synergy: Retinol, E, K2, & D need dietary fat and ratio balance.

• Gut damage compounds it: Endotoxin & low-grade inflammation block nutrient transporters and raise burn rate. So even adequate intake is inadequate that never reaches the gonads.

• Use caution with a diversity-lacking gym-bro diet: Chicken/rice/veg without organ meat means no heme iron, poor zinc:copper ratio, no choline. All meaning it’s easier for mitochondrial failure & dopamine to crash.

Evidence

Men on a micronutrient-dense Mediterranean diet show significantly lower ED risk.

Liao et al. (2024) found unexpectedly high ED rates in GLP-1 users → micronutrient depletion during rapid weight loss.

Fix

• Test then address (deficiencies): Confirm gaps where you can (RBC magnesium, serum zinc/copper, ferritin/serum iron/TIBC/saturation, plasma homocysteine, serum 25(OH)D, serum B9/B12). Track intake closely for 8–12 weeks. Then maintain.

• Fix the gut first for enhanced absorption (#4): Or you’re just pouring high-quality foods & supplements down the inflamed/leaky gut drain.

• Integrate the ancestral micronutrient stack: Oysters (zinc/copper/selenium/B12). Dark/organ meats (retinol, copper, folate). Egg yolks (choline, K2). Red meat (zinc, heme iron, carnitine). Full-fat dairy (calcium, magnesium, iodine).

• Balance the antagonists: Never megadose zinc without copper. Pair magnesium with a 2:1 potassium to sodium ratio. Keep retinol and D in ratio with E and K2.

• Replenish electrolytes aggressively: Magnesium (taurinate/pidolate /glycinate/chloride/sucrosomial). Potassium (coconut water/potatoes). Sodium. All critical for CO₂ tolerance & vascular relaxation.

• Cover the missed mitochondrial cofactors: B2/B3/B5/P5P/B9/B12, manganese, taurine, glycine, tyrosine to keep the ETC running.

• Add the NO-pathway lever: L-citrulline 6–8g/day (superior bioavailability to L-arginine which saw a 74% improvement in vasculogenic ED)

Factor #4 — Leaky gut & microbiota dysbiosis

How

• Modern environments spike zonulin & shred tight junctions: Isolated blue light. nnEMF. High Omega-6/low Omega-3 intake. High pesticide exposure. Low stomach acid. Excessive intense exercise without recovery. Poor circadian consistency. Endotoxin flood in → trigger systemic & neuroinflammation → blocks androgen & progesterone receptors.

• Low stomach acid lets the upper GI overgrow: Fermentation & pathogens grow leading to an imbalance of the “good” bacteria to “bad” bacteria ratio. Malabsorption of the zinc, copper, B-vitamins, & magnesium that testosterone synthesis depends on occurs.

• Training without fuel & fiber accelerates gut leak: Exercise drops gut blood flow. Missing soluble fiber (from fruit) gives a gut barrier breaking down faster than it rebuilds tanking thyroid conversion & NO bioavailability.

• Dysbiosis nukes the gut lining: Lost butyrate & SCFAs deteriorate gut lining enterocyte mitochondria → thin the mucus layer → leaky gut/more porous → amplify cytokines & reactive oxygen species → dysregulate vagus nerve & HPA axis.

Evidence

Schmidt et al. (2019) found 94% of inflammatory bowel disease patients reported ED symptoms. Geng et al. (2021) reported lower microbiome diversity in ED patients.

Fix

Heal the gut with the 6R framework.

1. Recon: Assess before you intervene

   1. Track at-home signals daily: Morning wood frequency and strength. Pre-caffeine AM blood pressure. Energy-to-anxiety ratio (spread across day). Digestion. Facial puffiness. Skin clarity. Headaches. Stool frequency & Bristol type. Breath.

   2. Order a comprehensive stool panel (like Genova or Doctor’s Data): Dysbiosis. Pathogens. Calprotectin. Zonulin. Pair with an organic acids test (OAT) for fungal and bacterial metabolites.

   3. Pull the systemic inflammation markers: hs-CRP. Homocysteine. Metabolic biomarkers.

   4. Run the gut-critical nutrient panel: RBC magnesium. Serum zinc & copper. Ferritin/serum iron/TIBC/saturation. 25(OH)D. Serum B9/B12 (w/ MMA if borderline).

   5. Map the gut-adjacent hormones: Total & free testosterone. SHBG. E2 (sensitive assay estradiol). Prolactin. LH/FSH. TSH. Free T3 & T4.

2. Remove: Strip the triggers

   1. Strip dietary triggers: Seed-oil PUFA. Gluten. Ultra-processed hyperpalatable combos (high-fat + high-carb + MSG + additives). Industrial dairy, soy, alcohol, & high-FODMAP foods.

   2. Cut food-additive barrier disruptors: Carrageenan. Polysorbate-80. Food dyes. Artificial sweeteners. All directly damage tight junctions.

   3. Eliminate Big Pharma and toxin loads: NSAIDs & PPIs. Glyphosate (choose organic). Fluoride (filter your water). Address environmental mold exposure.

   4. Calm the nervous system input (cross-ref #11, #12, #15): GABAergic compounds. Resting heart rate reduction/breathwork. Digital fast. Brain dumps. Analog systems. Time outdoors in green.

3. Reduce: Lower the systemic inflammation

   1. Bind endotoxin and metals: Modified citrus pectin 5–8g in between meals.

   2. Disrupt biofilm presence: Nattokinase 10,800 FU/day. NAC 600–1,200mg/day. Lactoferrin 250–500mg/day.

   3. Supply the repair raw materials: Bone broth 1–2 cups/day as food-first lever OR glycine 3–5g + collagen 10–20g/day to feed the mucus matrix & connective tissue

   4. Run targeted anti-inflammatory herbs: Black seed oil (Nigella sativa) 2–4g/day. Ginger 2–4g/day. Organic, heavy metal tested cinnamon 3–5g/day. Oregano oil 50–100 mg/day.

   5. Deploy the advanced peptide stack (every other day): BPC-157 250–500mcg/day (oral). KPV 500mcg–1mg/day.

      

4. Repair: Rebuild the barrier

   1. Restore stomach acid and motility before any lining-repair work: Sea salt (Diamond Crystal Iodized Salt or Jacobsen) & adequate sodium to supply chloride for HCl. Thiamine (B1) 100–200mg/day for gastric motility & vagal tone. Bitter herbs pre-meal (chamomile, gentian, dandelion, ginger) to trigger HCl and bile. Chew thoroughly and stop snacking so the migrating motor complex can clear the upper GI between meals. Test for and treat H. pylori if suspecting.

   2. Rebuild tight junctions and mucus: L-glutamine 20–30g/day (primary enterocyte fuel). Zinc-carnosine 75mg twice daily.

   3. Feed enterocytes directly: Tributyrin 500–1,500mg/day for SCFAs delivery direct to the gut lining with less dependence on a working microbiome.

   4. Titrate fiber: Top 3 sources (partially hydrolyzed guar gum (PHGG), acacia fiber, psyllium husk). Start @ 1g & add 1 g/week working up to 3g/day. Stop if poor digestion or cramps.

5. Reinoculate: Repopulate after the barrier is sealed

   1. Clear biofilms: Nattokinase 10,800 FU/day. NAC 1,200mg/day. Lactoferrin 250–500mg

   2. Run a pulsed antimicrobial for 2–4 weeks: Berberine 500–600mg, 2–3x/day. Oregano oil 50–100mg/day. Black seed oil 1–2g/day. Rotate between agents to avoid resistance.

   3. Reseed with food-first targeted probiotics: Saccharomyces boulardii (kefir, kombucha, kvass, miso). L. reuteri (kefir, sauerkraut, kimchi, yogurt). Spore-based Bacillus subtilis (natto, miso). Akkermansia muciniphila (pomegranate arils/juice/whole, blueberries, walnuts)

   4. Layer prebiotics once the lining is sealed: PHGG 5–10g/day or acacia fiber 5–10g/day to feed new flora.

   5. Reload the gut-healing micronutrients (full stack in #3): B vitamins. Zinc/copper. Retinol. Magnesium. Wild-caught fish. Grass-fed meats.

6. Rebalance: Dial in the maintenance phase

   1. Eat in a screenless parasympathetic state: Chew thoroughly. No eating while stressed or scrolling (cross-ref #12).

   2. Anchor meal timing to the clock: Eat a daylight diet on a consistent day-to-day schedule. Finish 3+ hours before bed (cross-ref #13, #15).

   3. Move after meals: 10–15 minutes to improve digestion, glycemic response, & bile flow.

   4. Treat sleep & stress as gut interventions: Poor sleep raises zonulin and endotoxemia within days (cross-ref #11, #13, #14).

   5. Protect the gut on training days: L-glutamine 10–20g + 20g collagen around intense or fasted/endurance work.

   6. Maintain the microbiome with food (full stack in #3): Organic. Mineral-dense. Fermented foods (yogurt, kefir, kimchi, miso, natto).

   7. Eat the occasional raw carrot salad between meals: One medium raw carrot dressed with a pinch of sea salt + a teaspoon of EVOO, & a splash of vinegar. The insoluble fiber binds bacterial endotoxin & excess estrogen out of the gut before they can be reabsorbed.

   8. Rerun Phase 1 Recon quarterly: Continue tracking at home signals daily & metabolic/inflammatory markers every 6 months

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Factor #5 — Nicotine

How

• Vasoconstrictor & a vascular toxin: Nicotine spikes sympathetic tone & constricts arteries acutely. Chronic use drives oxidative endothelial damage & kills NO bioavailability.

• Sympathetically pinned: Chronic nicotine elevates adrenaline/cortisol tone — the opposite of the parasympathetic state an erection requires (Factor #12).

• “Focus/dopamine” defense is a trap: Yes, nicotine bumps dopamine and acetylcholine acutely…but that’s exactly how it builds a habit loop downregulating baseline drive & speedrunning an anhedonic natural state.

Evidence

A double-blind, placebo-controlled RCT by Harte & Meston (2007) showed nicotine cut erectile response by 23%.

El-Shahawy et al. (2022) found e-cigarette users over twice as likely to report ED.

Fix

No dose will ever help your erectile quality.

Here’s exactly how to take the offramp:

Factor #6 — Weed

How

• THC suppresses the HPG axis: CB1 activation in the hypothalamus blunts GnRH pulses → lower LH/FSH → lower testosterone + higher prolactin (elevated prolactin alone tanks libido & erectile quality)

• Chronic use disrupts NO peripherally: Acute low-dose cannabinoids transiently vasodilate, but spamming too impairs endothelial NO signaling.

• The wrong blunt…of dopaminergic drive: Downregulated motivation/arousal circuitry compounds the hormonal hit.

Evidence

Pizzol et al. (2019) found that daily users had 2.7x higher ED odds than non-users.

Fix

• Taper to zero: Lower frequency. Take an extended break. Then reassess.

• Lower prolactin actively: B6 (P5P), zinc/copper (~12:1 ratio), selenium/iodine (~1:1 ratio) and tyrosine (1–2g on empty stomach in AM). Check prolactin on labs if libido stays low after quitting.

System 2: Dopamine Circuitry

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Raw dogging it isn’t sustainable. And if it’s your preferred path – expect max pain.

Fortunately it’s never been easier to take the offramp from your nicotine habit. (Ask how I know…)

After 10 months of testing, here’s what we’ve delivered:

• Why Quit

• Cold Turkey or Taper?

• Pre-Quit Setup

• Withdrawal Map

• First 72 Hours

• Tactical Toolkit

• Nicotine Mimetic Stack

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Why Quit

We can easily put together an entire article dedicated to the detrimental impacts, but here’s the abridged version of what chronic nicotine usage inflicts on your long-term health:

• Increases high blood pressure risk

• Overactivation of sympathetic nervous system

• Erectile dysfunction

• Increased pro-inflammatory response

• Increases periodontal disease risk

• Worsens gut microbiota composition, motility & function

• Immunosuppression

• Accelerates skin aging

• Hair loss

“Phys — spare me your nerd literature. Does this affect anyone in the real world?”

Checking in on Med Gold.

When I posted about there being no biological free lunch with Zyns. We got a lot of anecdotal feedback. Some of the first effects are felt on the drawdown in energy levels…& sexual vitality.

The most noticeable impacts though are felt on the cardiovascular front.

Gut function is not left untouched either.

And finally to why exactly we’ve cooked up this guide over the last year.

Cold Turkey or Taper?

Bioindividuality remains king and you know yourself best. That means the right method depends on:

1. How dependent you are

2. What your life looks like over the next two weeks (highest friction period)

3. What you’ve already tried (& failed with before)

I’ve found the below factors as a good set of proxies to choose the right path. You won’t fall cleanly into one bucket, but 5+ in a single column gives you an idea where to start.

Lean Cold Turkey If:

• ≤6mg pouches, fewer than 6 per day

• <2 years of consistent use

• 0–1 prior quit attempts

• Moderate withdrawal in past attempts (no big changes in cardiorespiratory measures – increased RHR or decreased HRV)

• Stable circadian regulation & sleep baseline (7+ hours nightly)

• Manageable current life stress

• Minimal alcohol use (<3 drinks/week)

• Schedule flexibility for the first 7 days

• No anxiety or low libido symptoms during prior quits

• Low cheap-dopamine load (limited degen tendencies = infinite scrolling + gaming + gambling)

Lean Structured Taper If:

• 8mg+ pouches or 8+/day (looking at you 28mg NYXX users)

• 2+ years of consistent use

• 2+ prior failed quit attempts

• Severe past withdrawal (elevated anxiety, poor sleep for >3 nights)

• Circadian dysregulated (i.e. not going to bed before 10 PM & waking up ~sunrise) & sleep already disrupted (<6 hours nightly)

• High allostatic stress load (work + relationship + finances)

• 4+ drinks/week or daily alcohol

• High susceptibility to caving (i.e. work, family obligations) in the next 10 days

• Anxiety or low libido during past quits

• Heavy cheap-dopamine consumption (high degen tendencies = infinite scrolling + gaming + gambling)

Taper Protocol

If you’re tapering, you obviously need to build in more time. Set a hard quit date & follow a simple, deliberate schedule. Don’t try to speedrun a protocol.

• Week 1: Drop strength (6mg → 3mg) at full frequency

• Week 2: Hold strength & cut pouches by 25%

• Week 3: Cut pouches by another 25%

• Week 4: Down to 2 pouches/day, then zero by end of week

• Quit date: Day 28.

Dopamine Audit (A Pre-req Before You Begin)

If there’s one area you need an honest audit of in advance of either protocol (and the one that one-shots most), it’s the dopamine baseline.

An anhedonic baseline is playing this on expert mode. A nicotine-saturated brain is a desensitized dopaminergic system. The absolute last condition you want to enter in with is a set of cheap, high-density dopamine sources normalizing an unnaturally high baseline.

Use these to assess if you’re ready to implement the protocol (yes = red flag):

1. Phone Reflex → Do you reach for your phone the moment you face uncertainty or silent boredom?

2. Sustained Attention → Does reading uninterrupted for 30 minutes feel like intense effort?

3. Social Media Fast Tolerance → Does a 24-hour social media fast feel difficult?

4. Audio Absent Movement → When you walk, do you need some form of audio on (i.e. podcast, music, or audiobook)?

5. Microvictory Threshold → Does completing a normal baseline task like meal prepping or finishing a workout fail to register as the least bit satisfying?

6. Morning Ritual → Is the first conscious act of your day reaching for your phone?

7. Solo Meal Capacity → Do you need a screen to eat a meal alone?

8. Stimulation Stacking → Do you regularly run two inputs at once (i.e. scroll with music)?

9. Silence Tolerance → Can you drive 20 minutes without sound?

10. Tab Hoarding → Are there 15+ tabs open on your phone or browser right now? Multiple feeds in active rotation?

11. Delayed Gratification → When was the last time you completed a 90-minute focused task without breaking for a hit of stimulation? If you can’t remember…

12. UV Walk → Does a walk in exceptional (high UV) weather feel flat?

A 7–10 day sensitization period before Day 1 is enough. Deprive to sensitize.

Pre-Quit Setup

Your system is your environment. Your environment determines the outcome.

Remember the Rule of 3

✅ 3 minutes to suppress the cravings
✅ 3 days to push past the withdrawals
✅ 3 weeks to form the new nic-free habit
✅ 3 months to rewire your brain chemistry

Pick the Right Launch Window

Quit into a busy weekend in a new environment. Attempting at home or office has every Pavlovian trigger working against your favor.

The ideal launch window is 3–4 days of social interactions, new experiences, & limited access to your autopilot’d routine. Whatever it takes to eliminate the habitual grab. A trip with your wife/girlfriend & kids. A bachelor party/wedding weekend. A long weekend traveling to friends or family.

You get the point. Remove yourself from your standard environments. And if you can’t do so over the entirety of the period, cycle in a new “third place” for a few days.

Clean the Environment

As important as the environment is with fat loss, it is equally important with your nicotine exit. Max the friction to the bad by eliminating every pouch from your possession. Your house. Your car. Your gym bag. Your desk.

An easy environmental lever as each can represents an opportunity to negotiate with yourself…and you don’t want to present yourself with that opportunity.

Stock Your Bored Mouth Substitutes

Into the later weeks, the nicotine pull becomes less neurochemical & more habit-based (i.e. reaching for the pouch out of habit/addressing boredom or uncertainty). We’ll discuss way more tactical tools below, but so much of the game up front is curing “bored mouth”.

✅ NZE Caffeine-Free Nootropic Pouches

✅ Zellie’s 100% Xylitol Gum

✅ Spry Xylitol Mints

✅ Xero Flavored Toothpicks

✅ Zevia/Swoon

Withdrawal Map

Read more

Few ever question it.

But look past the reductionist marketing and the research tells a different story. One worth paying attention to if you’re taking even 500 mg per day.

Because among certain populations at certain doses, vitamin C supplements come with a cardiovascular cost.

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The study that should change how you think about Vitamin C supplementation

In 2012, the Los Angeles Atherosclerosis Study (LAAS) tracked 573 healthy middle-aged adults aged 40–60 for a 3-yr period. The primary outcome measured was the carotid artery intima-media thickness (IMT). This is one of the most reliable early markers of atherosclerosis.

Researchers separated vitamin C intake into two categories: 1) from food sources & 2) from supplements.

What they found was a nearly 3X FASTER arterial wall thickening in the highest supplement quartile.

People taking no vitamin C supplements saw IMT progression of 7.6 µm/year.

While those in the 857–5,000 mg/day range saw IMT progression of 20.3 µm/year.

And the dose-response was linear: more supplemental intake = more progression (p-trend = 0.0009).

In the same study, vitamin C from food showed the opposite pattern.

The highest quintile of dietary vitamin C intake (~145–395 mg/day from actual whole food sources) was associated with less IMT progression (p = 0.008).

Some populations fare worse than others

The Iowa Women’s Health Study followed 1,923 postmenopausal women with diabetes for 15 years. After full adjustment for CVD risk factors, diabetes duration, & medications, women consuming ≥300 mg/day of vitamin C via supplements had significantly higher CVD & coronary artery disease mortality.

However worth noting — non-diabetic women from the same cohort had no association to increased CVD risk.

Two additional trials suggesting similarly:

1. In the WAVE trial, postmenopausal women with established coronary artery disease who took an antioxidant cocktail containing 1,000 mg vitamin C saw more coronary progression & higher all-cause mortality than placebo.

2. In the HATS trial, a similar antioxidant cocktail lowered HDL-C levels & blunted the lipid-lowering effects of statin + niacin therapy.

Why it happens

We know Vitamin C is a potent antioxidant. But at high intracellular concentrations, it shifts.

Vitamin C reduces Fe³⁺ to Fe²⁺ is what’s known as the Fenton reaction generating hydroxyl radicals & hydrogen peroxide.

In a healthy, iron-regulated system, it’s not a major concern. But inside atherosclerotic plaques/or with metabolically diseased individuals, redox-active iron accumulates and this reaction becomes locally destructive.

Food-sourced vitamin C doesn’t reach concentrations high enough for free radical byproducts to pose an issue. It also gets packaged with flavonoids, carotenoids, & a redox-balanced matrix of cofactors that supplements cannot replicate. Yet another case of nature winning. Many such of these.

Balanced Approaches > Maxxing

Your takeaway shouldn’t be to become vitamin C avoidant. Quite the contrary.

1. In a 6-year RCT of hypercholesterolemic men & women (ASAP trial), moderate combined supplementation of vitamin E (136 IU) + slow-release vitamin C (250 mg) 2x daily slowed carotid IMT progression by ~25–26% vs. placebo (p = 0.014).

2. Ellingsen et al. (2009) also found that elderly men who increased fruit / vegetable intake by only ~80g/day (& subsequently vitamin C intake by ~13 mg/day) led to significantly less IMT progression over 3 years.

Food-sourced vitamin C / moderate supplementation > chronic high-dose supplementation

Practical Takeaways

1. Food first.

150–300 mg/day in a bioavailable, cofactor-rich form.

2. If needing to supplement, choose moderate doses of natural extracts over ascorbic acid supplements.

Acerola cherry. Camu camu. Kakadu plum. Rose hips.

For most metabolically healthy men, ~400 mg/day vitamin C is the ceiling for chronic use. This saturates plasma without crossing into pro-oxidant territory.

Reserve 500–1,000 mg/day for an acute correction of seasonal sickness or documented deficiencies only. This can come in many forms. Once healthy again or levels normalize, drop back to food-first maintenance.

3. Let your biomarkers drive the decision.

Plasma ascorbate is what’s needed on bloodwork. Target 60–80 µmol/L where steady-state concentrations are met.

If you’re sitting in the mid-to-upper range from food alone, there’s very little evidence supporting additional supplementation.

Some adjacent markers to shape the full bioindividualized landscape:

hs-CRP: Elevated inflammatory load burns through antioxidant reserves faster. If CRP is chronically high, vitamin C turnover is higher and dietary intake needs to increase.

Ferritin & serum iron: High ferritin means more free iron available for the Fenton reaction. If ferritin is elevated (>200–300 ng/mL), high-dose vitamin C supplementation becomes unnecessarily risky.

Fasting glucose, fasting insulin, & HbA1c: A lack of metabolic flexibility & poor glucose metabolism amplifies vitamin C’s pro-oxidant potential and protein glycation effects.

Lipid panel (LDL-C, ApoB, oxLDL, Trig/HDL): The LAAS data showed the adverse effect of high-dose supplementation twice as much in those with elevated lipids in the top tertile.

4. Other factors influencing vitamin C status.

Several other factors increase vitamin C turnover and should influence how aggressively you’re going to prioritize intake:

➜ Training volume & intensity: High-volume endurance & intense resistance training increase the oxidative load. Match it to training load.

➜ Body composition: More lean mass increases high-ATP tissue demand.

➜ Heat exposure: Frequent sauna tips redox balance to an oxidative state and higher sweat-related micronutrient losses. Same goes with electrolyte losses.

➜ Excessive sunlight: UV radiation increases free radical production and subsequent antioxidant demand.

➜ High psychological stress loads: Cortisol & ascorbate compete for adrenal resources. Sustained stress via under-sleeping, overworking, & compounding life demands accelerates depletion.

➜ Age: Absorption efficiency declines and oxidative burden increases post-40.

➜ Restrictive diets: Carnivore. Keto. They will leave most functionally deficient.

➜ Acute illness: Immune activation depletes plasma levels. Needs will spike during infection, surgery, or recovery from injury.

If there’s anything that grinds my gears in the health space over the last year, it’s the “you need to be maxxing…” trend.

No. You shouldn’t be maxxing. Much more to come on this topic in the coming weeks.

For now, get your C from food.

Your friend,
Phys

If I had only 3 words to sum up what makes a successful dieting strategy, it’d be this: fix your environment.

Keep the tools around that minimize friction towards attaining the objective & increase any friction that veer you from that path.

To help you build the ideal dieting framework, here’s the set of tool I cycle through myself.

No aspartame. No seed oils. No fake ingredients that worsen gut function. Build the kitchen so that eating correctly eliminates willpower and the cut runs as a default system.

A couple notes before we begin:

→ If you’d like the 9-page PDF guide sent to you, just comment “Summer Shred Toolkit” and I’ll send it your way.

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→ For the complete fat loss strategy, visit here:

I. Volume Carb Swaps

Easy swaps of calorically dense versions for fiber-rich analogs that give you the same eating experience at a fraction of the caloric intake.

Retrograded Gluten-Free Overnight Oats — Easy hack to make your oats more filling: Microwave your oats the day before. Refrigerate for 12 hrs to retrograde the starch. Add your whey + fruit + cinnamon. More fiber. More volume. More satiating.

52USA Konjac Pasta — 12 calories per serving, clean ingredients (organic konjac, water, tapioca, citric acid), and the best texture of any shirataki on the market.

Miracle Noodle Konjac Rice — 5 calories per serving rice base for stir-fries & burrito bowls.

Miracle Noodle Egg White Pasta — 50 calories per serving. Satiating, protein-dense pasta alternative.

Palmini Hearts of Palm Pasta — Plant-based, potassium-dense noodle with an al dente texture. Holds sauce better than zoodles. Doesn’t get watery like shirataki.

Palmini Hearts of Palm Rice — Holds up in stir-fries where cauliflower rice disintegrates.

Spaghetti Squash — Roast once on Sunday, shred into noodles that last 2—3 days. A whole squash runs ~130 calories & yields ~6–8 cups of finished volume.

Butternut Squash — Naturally sweet, fiber-dense & high volume per calorie. Cube, toss with salt, roast at 425°F for 30 min.

Zucchini Noodles (Zoodles) — Spiralize fresh or buy pre-spiralized. Pasta swap. 2-minute sauté for hot dishes. Nearly zero caloric cost.

Cauliflower Rice — Sub for rice bases/bowls. ~25 cal per cup. Trader Joe’s Organic = my weekly staple.

Bibb Lettuce Wraps — Default tortilla swap option when you want a wrap.

Egg White Wraps — When you actually need a tortilla. 30—50 cal/wrap. Original, Southwest, Everything Bagel Wraps. Clean ingredients. No seed oils/modified starch.

Lundberg Organic Whole Grain Rice Cakes Cinnamon Toast — 70 cal each. Satisfies the crunch. Pre-training vehicle for peanut butter powder or salsa.

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II. Zero / Low-Cal Beverages & Hydration

A dual win: 1) eliminate the calories & 2) use the drinks themselves as friction- reducers for mid-afternoon cravings.

Zevia — Stevia-sweetened soda. You don’t even have to worry about the artificial sweeteners anymore.

Seltzer (LaCroix / Spindrift / Bubly / Kirkland) — Any seltzer brand. Spindrift is king. Kirkland (Costco) a good budget pick.

Kettle & Fire Bone Broth — 35–45 cal per cup. 10g protein. Glycine-dense. No better tool to satisfy the warm & savory craving.

Herbal Teas — Teas (especially hot) are great for appetite suppression & satiety boost.

Electrolytes — Tons of great brands out there. Highly specific to bioindividualized requirements. Match Na/K/Mg/Ca/Cl to your sweat rate, training load & baseline dietary micronutrient intake.

Matcha — Smoother energy curve than coffee for afternoons from the L-theanine content. Opt for ceremonial grade & USDA organic. Verify the “Sold By” isn’t an Alibaba-coded dropshipper.

Recipe: Nighttime Inositol-Glycine Sweet Tea

Functional benefits & sweetness without stevia’s bitterness. Inositol supports insulin sensitivity. Glycine supports sleep.

• 12 oz boiling water

• 1—2 Honey Vanilla Herbal tea bags

• 3—5g glycine powder

• 2—3g myo-inositol powder

• Squeeze of lemon

Stir until dissolved. Drink hot or pour over ice.

III. High-Volume Low-Cal Produce

If there’s one variable to rule them all, it’s volume. These are the highest-ROI produce choices for exactly that. Each category is ranked by a composite score based on pure calorie density, satiety index, & volume-to-calorie ratio.

Fruit (Ranked)

1. Watermelon — 30 kcal/100g · 0.4g fiber · 91% water. The king of volume-per-calorie. Two full cups runs ~90 cal. Peak summer seasonal pick.

2. Strawberries — 32 kcal/100g · 2.0g fiber. Highest fiber-to-sugar ratio of any berry. 500g lands at ~160 cal with 10g fiber.

3. Cantaloupe — 34 kcal/100g · 0.9g fiber · 90% water. Summer peak. Dense beta-carotene. Slower eating than watermelon because of density.

4. Honeydew — 36 kcal/100g · 0.8g fiber. Near-identical to cantaloupe with a cleaner sweetness.

5. Raspberries — 52 kcal/100g · 6.5g fiber. The highest fiber content of any fruit on this list.

6. Blackberries — 43 kcal/100g · 5.3g fiber. Lower-sugar berry with the same polyphenol profile as blueberries.

7. Peaches & nectarines — 39 kcal/100g · 1.5g fiber. Summer peak.

8. Blueberries — 57 kcal/100g · 2.4g fiber. Slightly higher cal than the other berries but anthocyanin density is unmatched.

9. Navel/blood oranges — 47 kcal/100g · 2.4g fiber. Ranked highest on the Holt satiety index among fruits. Peel format slows eating and pith fiber extends fullness.

10. Apples — 52 kcal/100g · 2.4g fiber. Pectin soluble fiber forms a satiety gel in the gut.

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Raw Crunch Vegetables (Ranked)

1. Cucumber — 15 kcal/100g · 0.5g fiber · 95% water. Pound-for-pound the lowest calorie density on this list. Eat by the whole cucumber w/ sauce of choice.

2. Celery — 16 kcal/100g · 1.6g fiber · 95% water. They’re not “negative-calorie” but it’s closer with celery than almost anything else. 6 cal per stalk.

3. Iceberg lettuce — 14 kcal/100g · 1.2g fiber · 96% water. Not nutrient-dense, but for pure volume crunch it’s excellent. Great taco shell.

4. Radishes — 16 kcal/100g · 1.6g fiber. Peppery bite. Near-zero cal. Pairs with almost anything.

5. White button / crimini mushrooms — 22 kcal/100g · 1.0g fiber. Meaty texture. Excellent bulk-up for ground beef or eggs. Much better when cooked.

6. Cherry tomatoes — 18 kcal/100g · 1.2g fiber · 95% water. Technically a fruit, but you get the point.

7. Bell peppers (all colors) — 31 kcal/100g · 2.1g fiber. Red has 3x the vitamin C of orange juice per serving. Sweet crunch vehicle.

8. Sugar snap peas — 42 kcal/100g · 2.6g fiber. Higher cal than the others here but higher fiber & a satisfying whole-pod chew.

9. Jicama — 38 kcal/100g · 4.9g fiber. Way underused. Chopped into fries or sticks & seasoned well.

10. Kohlrabi — 27 kcal/100g · 3.6g fiber. Dense fiber, potassium, Vit C content. Peels like a radish. Best roasted.

Cruciferous (Ranked)

1. Cauliflower — 25 kcal/100g · 2.0g fiber. Riced, roasted, mashed, or eaten raw. Most versatile crucifer.

2. Green cabbage — 25 kcal/100g · 2.5g fiber. Shredded raw in slaws, fermented as kraut, sautéed in butter. One head is ~6 cups of finished volume.

3. Napa cabbage — 16 kcal/100g · 1.0g fiber. Softer than green cabbage. Works raw in salads where regular cabbage is too dense.

4. Broccoli — 34 kcal/100g · 2.6g fiber. Roasted & seasoned at 425°F.

5. Red cabbage — 31 kcal/100g · 2.1g fiber. 10x the anthocyanins of green cabbage. Shred for tacos, slaws, or stir-fries.

6. Broccoli rabe (rapini) — 22 kcal/100g · 2.7g fiber. Grandma Phys classic. Sautéed with garlic & chili flakes.

7. Broccolini — 35 kcal/100g · 2.5g fiber. Milder & sweeter than broccoli. Longer tender stems. Faster to cook.

8. Brussels sprouts — 43 kcal/100g · 3.8g fiber. Highest-cal cruciferous here, but also highest fiber. Halve, drizzle balsamic glaze, & roast cut-side down for caramelized flavor.

9. Romanesco — 28 kcal/100g · 3.2g fiber. Broccoli-cauliflower hybrid. Same profile as cauliflower with a nuttier, more complex flavor when roasted.

10. Collard greens (sautéed) — 32 kcal/100g · 4.0g fiber. Technically cruciferous. Avoid raw. Ideal braised or as a wrap replacement for heavy flour tortillas.

Pantry & Frozen Volume

Frozen cherries — ~90 cal per cup. Let the cold slow eating pace & the tartness satisfy without triggering more.

Frozen dragonfruit — ~80 cal per cup. Potassium & magnesium-dense. Ideal for tropical smoothies.

Frozen mango chunks — ~100 cal per cup. Partially thawed. Eats like sorbet.

Frozen pineapple chunks — ~80 cal per cup. Bromelain is elite for digestion. Blends into protein smoothies for volume at low caloric cost.

Canned pumpkin purée (100% pumpkin) — 40 cal per half cup. Stir a spoonful into Greek yogurt, oats, or a shake for hidden volume & 3g fiber.

Grillo’s dill pickles — Light pre-training fuel. Great pre-HIIT. Live fermented, crunch and salt in one bite. Also one of the most underrated craving killers.

Raw kimchi & sauerkraut — Fermented vegetables to support gut microbiome diversity = enhanced ghrelin (hunger-hormone) signaling. Near-zero cal. Serve cold as a side to any protein.

Air-popped popcorn — ~30 cal per cup. Season with Tajin, Old Bay, or nutritional yeast. The volume-to-calorie ratio tough to beat.

Frozen spinach (chopped, whole-leaf) — Denser nutrition/$ than fresh. Thaw → squeeze dry → stir into eggs or shakes for more volume.

IV. Fiber & Satiety Stack

If your gut is in a healthy condition, fiber is the most underused satiety lever available. Soluble fiber absorbs 10–40x its weight in water → forms a viscous gel → stomach stretches → receptors in the gut lining fire signals up the vagus nerve to the brain → brain reads as fullness.

Psyllium Husk Powder — Viva Naturals mixes best. 5g in 12 oz of water 15–20 minutes before your biggest meal. Start low & work up to 5—10g.

Organic Chia Seeds — Soak in overnight oats or kefir for more filling breakfast. Expand 10—15x in liquid. Cheap alternative to psyllium.

Organic Inulin Powder — Prebiotic soluble fiber with mild sweetness. Ideal for overnight oats & yogurt bowls.

V. Bored Mouth Cures

Japanese culture understands the idea of “you’re not hungry, you’re just bored” best with the term kuchisabishii (口寂しい), which translates to “lonely mouth”. Some of my favorite tools for curing bored mouth.

Zellie’s 100% Xylitol Gum — My top gum pick. Xylitol has the oral health upside and the chew itself mitigates any snack impulse.

Pur 100% Xylitol Gum — Another clean gum. Cheaper alternative with a little less flavor.

Spry Xylitol Mints — Berry > Cinnamon > Peppermint > Lemon

Brushing your teeth after the last meal — Free one, yet under-discussed. Toothpaste makes food unappealing for an hour. A Pavlovian signal that the eating window has closed.

VIII. Sweetener Toolkit

Not all zero-calorie sweeteners are equal. Some of the ones we’re mitigating: aspartame, sucralose, acesulfame potassium, & saccharin.

Allulose — ~70—90% as sweet as sugar. Behaves exactly like sugar in heat → caramelizes, browns, dissolves. The only sweetener to use in baking or anything reduced on a stove.

Myo-inositol — Mild sweetness plus functional benefits (leptin/insulin sensitivity + anxiety reduction). 2—3g stirs into a hot drink well.

Glycine — ~70% as sweet as sugar. Clean, sweet taste Pairs synergistically with inositol. Also S-tier for dropping body temperature & reducing time to fall asleep at ~3—5g before bed.

Lakanto Monk Fruit Drops — Cleaner aftertaste than stevia if you dislike bitterness.

VI. Flavor Weapons

The path to upgrading every bowl.

Sauces & Dressings

Primal Kitchen BBQ, Ketchup, Steak Sauce, Mayo — Avocado oil base without seed oils, sugar, or corn syrup. One of only a few “mainstream” clean-sauce brand that actually delivers on flavor.

Noble Made Buffalo — Personal favorite buffalo sauce made with extra virgin olive oil.

True Made Foods No Sugar Added Ketchup — Sweetened with butternut squash, carrots, & apple instead of HFCS or sucralose. The cleanest no-sugar ketchup made.

G Hughes Sugar-Free BBQ or Asian Marinades — Ideal when you need a Asian-style or sweet-glaze flavor profile for bowls/stir-fry.

Fresh Salsa or Pico — 15–20 cal per 1/4 cup. Staple for any TexMex/Southwestern bowls. Make your own or buy refrigerated. Trader Joe’s selection also strong.

Huy Fong OG Sriracha — Still the best sriracha. Small amount of sugar but the flavor cannot be topped.

Coconut Aminos — Deep umami. 65% less sodium than soy sauce. Slightly sweet naturally.

White Miso — ~25 cal per tbsp. Savory flavor. Great for broths, marinades, & dressings with small quantities. Fermented so also great for digestion.

VII. Spreads & Nut Butter Hacks

Organic Peanut Butter Powder — Defatted peanut powder. 1/3 the calories of peanut butter. Mix with water for spread → add cocoa for chocolate peanut butter mousse.

Powdered Almond Butter Powder — The defatted almond butter powder alternative.

Organic Cacao Powder — ~3g carbs per tablespoon. Clean, intense chocolate. Foundation of any high-protein chocolate dessert hack.

VI. Flavor Enhancers

Bragg Nutritional Yeast — 45 cal per 2 tbsp. Cheesy-nutty umami. High B1 (thiamine). On popcorn, eggs, & roasted veggies.

Everything Bagel Seasoning (Trader Joe’s / Costco) — Zero-cal flavor for eggs, Greek yogurt based dips, & cottage cheese.

Old Bay — How to take baked sweet potatoes to the next level.

Mina Harissa — Newest addition to my lineup. North African pepper paste. ~15 cal per tbsp. Elevates marinades, bowls, & roasted veggies with minimal calorie cost.

IX. High-Protein Desserts & Frozen Snacks

The Base Ingredients

Ninja Creami — Remains my favorite health investment over the last couple years. Once you acquire, you’ll wonder how you ever operated in your B.C. era (Before Creami). It pays for itself in saved calories within a month.

Nonfat Plain Greek Yogurt — 17g protein, 90 cal per 6 oz. The foundation of half the recipes here.

2% Good Culture Low-Fat Cottage Cheese — 14g protein per 4 oz. Clean ingredients (milk, live cultures, salt). No gums or thickeners.

Siggi’s Nonfat Plain Skyr — Highest protein density of the three (17g per 5.3 oz), Icelandic-style. Thicker than Greek yogurt. Amazon

Transparent Labs Grass-Fed Whey Isolate — Minimal ingredient. No artificial flavors or sweeteners. Chocolate and vanilla are the workhorses. Amazon

Equip Grass-Fed Collagen Peptides — 14g hydrolyzed collagen peptides per scoops. Dissolves well into any hot drink.

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The Recipes

Recipe: Collagen Hot Cocoa

Evening wind-down, sleep support (glycine), & dessert in one mug.

• 12 oz hot water or unsweetened almond milk

• 2 scoops grass-fed collagen peptides powder

• 1 tbsp raw cacao powder

• 3—5g glycine

• 2—3g myo-inositol

• Pinch of sea salt

• Allulose or monk fruit (if you’d like more sweetness)

Blend for ~20—30 seconds until frothy. ~120 cal.

Recipe: Ninja Creami Chocolate Peanut Butter Ice Cream

More Ninja Creami recipes to come this summer. But for now, here’s a basic one to make a full pint at 450 cal & 50g protein total.

• 1 cup Good Culture 2% cottage cheese

• ½ cup unsweetened almond milk (or Fairlife skim)

• 1 scoop chocolate whey isolate

• 2 tbsp powdered peanut butter

• 1 tbsp raw cacao powder

• 2 tbsp allulose (what prevents the rock-solid freeze)

• ¼ tsp sea salt

• ½ tsp vanilla extract

Blend smooth, pour into Creami pint, freeze 24 hours, spin on “lite ice cream” setting, add another splash of milk, re-spin.

Recipe: Protein Fluff

High-speed blender or stand mixer, 5 minutes, massive bowl of mousse.

• 1 scoop whey isolate

• ½ cup frozen berries

• 2–3 tbsp unsweetened almond milk

• Sweetener to taste

Blend on high, adding almond milk tablespoon by tablespoon until the mixture quadruples in volume. Eat immediately. ~180 cal & 25g protein.

Recipe: Whey Protein Mousse (no blender)

• 1 scoop whey isolate

• 2 tbsp cold water ( too much ruins it)

• Pinch of salt

Shake hard in a closed container for 30 seconds. The texture transforms into a dense mousse. Top with cinnamon & fresh berries.

Recipe: Greek Yogurt + Sugar-Free Pudding Hack

• 1 cup nonfat plain Greek yogurt

• 1 tbsp dry Simply Desserts sugar-free pudding mix (chocolate, vanilla, or banana)

Mix for 60 seconds. The texture transforms into dense pudding instantly. ~130 cal, 20g protein. Simply Desserts is stevia-and-erythritol sweetened.

Recipe: Frozen Banana Nice Cream

• 1 frozen banana, sliced

• 1 tbsp raw cacao

• Splash of unsweetened almond milk

Blend until smooth. ~110 cal. Real ice cream texture.

Recipe: Cottage Cheese Chocolate Freeze

• ¾ cup Good Culture cottage cheese

• 1 tbsp raw cacao

• Sweetener to taste

• Small handful of frozen berries

Blend smooth, transfer to bowl, freeze 45 minutes (not fully frozen, just firm). Dense chocolate mousse texture.

Ready-to-Grab

GoodPop No Added Sugar Popsicles — Real fruit. Organic. No artificial sweeteners. ~25–50 cal per pop.

Final Word

It’s 2026. We no longer need to make dieting down painful. The tools are everywhere to make your life easier in getting there.

This year is the year you’ll stack the environment in your favor & build your dream physeek. Simple.

Until next week.

Your friend,
Phys

Ask someone about the origins of AI as we know it today and they’ll probably trace it back to 2022 when ChatGPT launched and became the fastest consumer app to hit 100M users in just 2 months. But few know the story actually started in 1956 at Dartmouth. It felt like it blossomed out of thin air, but it was really just building for more than seven decades.

Peptides follow the same arc – Amara’s Law:

“We tend to overestimate the effect of a technology in the short run & underestimate the effect in the long run.”

This idea is best modeled by the Gartner Hype cycle.

After a few mainstream podcasts and wave of viral X posts in 2025, “peptides” became the buzzword that means everything and nothing at the same time. To most, it all became relevant overnight.

But this short amino acid chain science has been building for over a century. Albeit quietly. In Soviet military labs, University of Arizona basements, Gila monster saliva, & Croatian gastroenterology departments.

As we write this in April 2026, we’re sitting near the peak of inflated expectations. And a sharp bifurcation is forming. The hype riders vs. the elite practitioners. The former as tactic hunters. The latter as strategic health infrastructure builders. If you’re reading this — congrats on finding your way into the latter.

Downloadable PDF plot below for detailed viewing (abridged version):

Peptide Hype Cycle

525KB ∙ PDF file

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1902–1953: The birth of peptides

The first peptide ever identified came in 1902 when William Bayliss & Ernest Starling discovered secretin, a chemical messenger released from the gut lining signaling the pancreas to secrete digestive enzymes.

Two decades later in 1921, Frederick Banting & Charles Best isolated insulin from canine pancreases. By 1922, a dying 14-year-old diabetic named Leonard Thompson received the first human injection.

This marked the first exogenous peptide therapy ever used in humans. Insulin proved the model that every peptide discussed here follows: isolate or synthesize a signaling molecule → deliver it exogenously → restore or redirect a biological process.

In 1954, chemist Vincent du Vigneaud rang in the era of synthetic peptide design as we know it today. He completed the first total synthesis of oxytocin & vasopressin assembling peptides amino acid by amino acid proving they can be built from scratch. He won the Nobel Prize the following year.

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1963–1979: The infrastructure gets built

Prior to 1963, making peptides in a lab was an arduous process. Every amino acid had to be coupled individually in solution, purified, & verified. Bruce Merrifield came along and invented solid-phase peptide synthesis (SPPS) that won him the Nobel Prize in Chemistry in 1984. SPPS automated the process by anchoring the growing chain to an insoluble resin bead making peptide production scalable.

Without SPPS, no peptide sold today would exist. Meanwhile, behind closed doors in the USSR, a mastermind was developing a parallel peptide vector.

Bioregulators: The classified Soviet program

In 1971, a military physician named Vladimir Khavinson started extracting peptide complexes from animal organs at the Kirov Military Medical Academy in Leningrad. The classified program objective was to protect soldiers, cosmonauts, & athletes from radiation exposure, extreme cold, & operational stress.

Khavinson’s team isolated short-chain peptides (2 to 4 amino acids long) from the thymus, pineal gland, brain cortex, prostate, & retina of calves. These became the first peptide bioregulators:

• Thymalin (from the thymus) regulated cellular immunity.

• Epithalamin (from the pineal gland) restored melatonin production and endocrine function.

Khavinson eventually proposed these ultra-short peptides could bind directly to DNA promoter regions and modulate gene expression. These were epigenetic switches that told aging cells to behave younger.

By 1982, Thymalin received formal registration for medical use in the USSR. Six peptide pharmaceuticals would eventually be approved for clinical use.

It wouldn’t be for another decade until the rest of the world heard of bioregulators.

Growth hormone secretagogues: An accidental discovery

In 1977, endocrinologist Cyril Bowers at Tulane University was studying small opioid-like peptides (enkephalin analogs) when he noticed certain chemical modifications that caused pituitary cells to release growth hormone.

This was the birth of the growth hormone secretagogue field.

1980–1989: Three parallel threads

The 1980s saw three separate research programs develop in parallel.

Thread 1: GH secretagogues mature

By 1984, Bowers synthesized GHRP-6 making it the first synthetic hexapeptide to dose-dependently release growth hormone. He was building the key before anyone knew the lock existed, which became known as “reversed pharmacology”. GHRP-6 worked through a receptor nobody had identified yet.

The endogenous hypothalamic hormone GHRH was discovered shortly after. Interest in GHRPs faded as most assumed GHRH was the primary GH regulator. That assumption turned out to be wrong. GHRP-6 & GHRH operated through completely distinct receptors and had synergistic effects on GH release.

Sermorelin, the synthetic form of GHRH, entered development during this period and would eventually receive FDA approval in 1997 as a diagnostic agent for GH deficiency.

Thread 2: Melanocortins emerge in the desert

At the University of Arizona, biologist Mac Hadley & chemist Victor Hruby were modifying alpha-melanocyte-stimulating hormone (α-MSH) — a naturally occurring peptide involved in skin pigmentation. Their goal was to create a stable synthetic analog that could induce tanning without UV exposure helping to reduce skin cancer risk.

Melanotan I came first: a linear 13-amino-acid peptide that closely resembled natural α-MSH but lasted longer in the body.

Then came Melanotan II: a cyclic heptapeptide that was much more potent and metabolically stable. Most peptides are straight chains where enzymes can attack the exposed ends and break them down fast. MTII had no free ends for enzymes to grab onto giving it longer lasting effects.

MT-II also bound to more than just MC1R (pigmentation) but also MC3R, MC4R, and MC5R. All of which were receptors involved in sexual function, appetite, & energy balance.

Thread 3: Soviet bioregulators go clinical

By the mid-1980s, Khavinson extracted over 20 peptide complexes from animal organs and synthesized 15 additional short peptides. Thymalin and Epithalamin had been in clinical use within the Soviet military medical service. Others followed: Cortexin (brain cortex, for cerebral function), Prostatilen (prostate), Retinalamin (retina).

Bioregulator treatment slowed age-related biomarker decline and suppressed tumor development in animal models showing lifespan increases of 20-40%.

But the work was still classified & published in Russian journals leaving it entirely invisible to Western science until the Soviet Union collapsed.

1990–1999: The discovery decade

Nearly every major category of peptide discussed online today has its roots in the 1990s.

BPC-157: Gastric juice yields a healing compound

In the early 1990s, Croatian pharmacologist Predrag Sikirić based at the University of Zagreb isolated a stable pentadecapeptide (15 amino acids) from human gastric juice. They named it Body Protection Compound-157 (BPC-157).

Sikirić sought to understand why the stomach heals its own lining despite constant exposure to hydrochloric acid. His team found a peptide fragment from a larger protective protein having cytoprotective effects across many tissue types including the gut, tendons, ligaments, muscle, bone, & vasculature.

Over the next three decades, Sikirić’s lab would produce the vast majority of published BPC-157 research: acceleration of wound healing, reductions in inflammation, & protection of GI lining from previous damage.

Exendin-4: The Gila monster connection

The Ozempic story is most unique in its origins. In 1991, endocrinologist John Eng was studying the venom of the Gila monster, a venomous lizard native to the American Southwest, when he identified a 39-amino-acid peptide called Exendin-4. It had extensive structural homology to human GLP-1, the incretin hormone that stimulates insulin secretion after meals.

The big difference between endogenous GLP-1 & Exendin-4: the former has a plasma half-life of ~2 min & Exendin-4 has a natural mutation extending its half-life to 2.5 hours.

After struggling to find institutional support, Eng patented Exendin-4 personally. He partnered with Amylin Pharmaceuticals years later to develop what became the first GLP-1 receptor agonist: exenatide.

Retrospectively, this was the start of a metabolic revolution. In 1991, the response was silence.

The Soviet collapse and bioregulator declassification

When the Soviet Union collapsed in 1991, Khavinson’s classified research became accessible. The St. Petersburg Institute of Bioregulation and Gerontology was established. The peptide bioregulator program transitioned from military secrecy to an open scientific publication.

Khavinson refined his approach as he shifted from crude organ extracts (Cytomaxes) to chemically synthesized short peptides (Cytogens). Epitalon became the most internationally recognized molecule from this program and one becoming increasingly popular today. In 2025, a UK-based group published the first independent replication confirming dose-dependent telomere extension in normal human cells

The synthetic bioregulator Thymogen (a dipeptide for immune correction) also emerged from this era. By the 2000s, Khavinson amassed over 105 patents and 775 published papers spanning four decades of research.

GH secretagogues: 2nd generation

The GHRP family expanded rapidly through the 1990s.

GHRP-2 (pralmorelin) was synthesized as a more potent second-generation analog having a stronger GH release than GHRP-6 with better sustained elevation over time. Hexarelin followed with similar potency.

In 1998, Novo Nordisk characterized ipamorelin as the first selective growth hormone secretagogue. Unlike GHRP-6 and GHRP-2, ipamorelin released GH without spiking cortisol, ACTH, or prolactin.

Melanotan II: Too hard to ignore (*winks*)

In 1996, the Arizona team ran a Phase I clinical trial of Melanotan II to evaluate its tanning efficacy. Five low-dose subcutaneous injections produced visible skin darkening. The tanning worked.

But MT-II’s broader receptor binding demonstrated unforeseen outcomes…inducing erections in each male subject. MC4R activation in the central nervous system was triggering penile erection through hypothalamic / spinal pathways independent of sexual arousal.

Many of the forums & Reddit threads have been detailing these very cases over the last decade.

Despite this not being the intended objective, it redirected the entire melanocortin research program. Sexual dysfunction became the new target. PT-141 (bremelanotide) was synthesized by Palatin Technologies as a derivative of the MT-II scaffold, which optimized for central melanocortin activity with reduced melanogenic effects.

Thymosin Beta-4 & TB-500

Allan Goldstein first described Thymosin Beta-4 (TB4) in the 1960s, but it didn’t gain traction until the 1990s. TB4 functions by maintaining a ready-to-deploy reservoir that cells can rapidly assemble into structural filaments when tissue is damaged. This is what allows reparative cells like fibroblasts, stem cells, & endothelial cells to physically migrate into a wound site and start rebuilding.

The synthetic fragment TB-500 was a TB4 fork, which distilled it into a shorter, more accessible molecule. It’s now become one of the most widely used recovery peptides in sports performance & recovery alongside BPC-157.

2000–2009: From labs to prescription pads

GLP-1 goes pharmaceutical

After a 14-yr period, the FDA approved the Gila monster peptide (exenatide (Byetta)) as the first GLP-1 receptor agonist for type 2 diabetes in 2005.

Novo Nordisk watched closely and began developing its own GLP-1 analog. Liraglutide used a different strategy. They attached a fatty acid chain (C16) to the GLP-1 peptide, allowing it to bind reversibly to albumin in the bloodstream. This slowed renal clearance and extended the half-life enough for a single daily dosing. It received EU approval in 2009 and went on the market as Victoza.

CJC-1295: Long-acting GHRH

ConjuChem Biotechnologies developed CJC-1295, a modified version of GHRH(1-29) with a Drug Affinity Complex (DAC) that bound to serum albumin extending its half-life to 6-8 days. The “no-DAC” version (Mod GRF 1-29) used the same GHRH analog without the albumin-binding complex. It was shorter acting requiring more frequent dosing, but it preserved pulsatile GH release that mirrors natural endocrine rhythms. Phase II trials showed dose-dependent GH increases of 2-10x sustained for 6+ days after a single injection.

Khavinson publishes landmark human data

In 2003, Khavinson & Morozov published the results of a 6-8 year clinical assessment of Thymalin & Epithalamin in 266 elderly subjects. The bioregulators normalized immune function, endocrine markers, & cardiovascular indices.

Mortality in the treatment groups was 28% lower than controls.

Though the story was compelling, the data came from Russian institutions and was published in Russian journals, which was met with Western skepticism.

Thymosin Alpha-1: Approved everywhere but the US

Thymosin Alpha-1 (Ta1) is a 28-amino-acid peptide derived from thymus tissue. It was approved under the brand name Zadaxin in 36 countries for hepatitis B, hepatitis C, & as an immunotherapy adjunct, though it’s never been submitted for FDA approval in the US.

Nootropic peptides: Selank and Semax

Two synthetic peptides with nootropic & anxiolytic properties emerged from Russian pharmaceutical development.

Semax: a synthetic analog of ACTH(4-10) with a Pro-Gly-Pro tripeptide extension known for its neuroprotection and was approved in Russia for anti-stress, cognitive enhancement, stroke recovery, & ADHD.

Selank: a synthetic analog of the immunomodulatory peptide tuftsin, also with a Pro-Gly-Pro extension showing anxiolytic effects (comparable to benzodiazepines without side effects/dependency risk) and was approved in Russia for generalized anxiety.

GHK-Cu: A copper tripeptide

In 1973, biochemist Loren Pickart discovered GHK-Cu (glycyl-L-histidyl-L-lysine complexed with copper) as a naturally occurring human tripeptide first identified in human plasma.

Endogenous concentrations decline significantly with age → plasma levels at age 60 (~80 ng/mL) are less than half at age 20 (~200 ng/mL).

GHK has now become a staple in the cosmetic & regenerative health space either applied topically or applied subcutaneously.

Through the 2000s, its research profile widened considerably given it modulates expression of hundreds of genes tied to:

• wound healing

• collagen synthesis

• antioxidant defense

• extracellular matrix remodeling

Mechanistically, GHK-Cu is unique in that it acts like a bioregulator but drives direct tissue repair like a healing peptide. And that’s why we’re seeing it show up in so many different protocols.

2010–2019: The pharmaceutical explosion

GLP-1 becomes a metabolic optimization story

The 2010s marked the shift of GLP agonists from a niche T2 diabetes treatment to one of the most powerful metabolic optimization tools in existence.

After liraglutide’s (Victoza) 2010 FDA approval in 2010 for type 2 diabetes, Saxenda (liraglutide at higher doses) became the first GLP-1 approved specifically for weight loss.

Shortly after, dulaglutide (Trulicity) arrived with once-weekly dosing. Then in 2017, semaglutide (Ozempic) shifted the entire metabolic landscape.

By 2019, oral semaglutide (Rybelsus) proved that a peptide could survive stomach acid and reach therapeutic levels orally. This was done via a co-formulated absorption enhancer called SNAC that raised local stomach pH and improved absorption.

Melanocortins reach the market

In 2014, the EU approved Melanotan I (Scenesse) for a rare condition causing extreme photosensitivity. This marked the first regulatory validation of melanocortin-based pigmentation therapy. The US followed with FDA approval in 2019.

That same year, bremelanotide (PT-141) sold under the brand name Vyleesi received FDA approval for hypoactive sexual desire disorder in premenopausal women.

Melanotan II has never received regulatory approval though. Its non-selective receptor binding (what made it versatile) also caused some regulatory complications.

The underground peptide economy gains momentum

By the late 2010s, a grey market peptide economy matured. Compounding pharmacies were focused on formulating BPC-157, TB-500, ipamorelin, & CJC-1295 for clinical use under physician prescription. The “Wolverine Stack” (BPC-157 + TB-500 for accelerated tissue repair) entered the world of sports medicine & decentralized biohacking communities.

Mitochondrial peptides are born

A newer class of peptides derived from mitochondrial DNA began attracting research attention.

MOTS-c: a mitochondria-derived peptide known for its effects on metabolic regulation & insulin sensitivity.

Humanin: another mitochondria-derived peptide known for its neuroprotective properties in Alzheimer’s disease models & anti-apoptotic effects.

AOD-9604: a modified fragment of HGH developed specifically for its fat-reducing properties without the diabetogenic effects of full-length HGH. It received Generally Recognized as Safe (GRAS) status from the FDA as a food ingredient.

2020–2026: Peak hype + peak friction

The GLP era

In 2021, Wegovy (semaglutide) received FDA approval for chronic weight management.

Average weight loss in clinical trials = ~15% of body weight. The GLP-1 era officially arrived.

In 2022, tirzepatide (Mounjaro) received FDA approval as the first dual GLP-1/GIP agonist for T2 diabetes.

Clinical trials showed ~21% average weight loss.

In 2023, tirzepatide (Zepbound) received obesity approval. By 2024, GLP-1 drug sales neared $14 billion.

By the end of 2024, soaring demand brought on new shortages. Compounding pharmacies began producing semaglutide copies under shortage exemptions. Chinese peptide imports to the US doubled to $328 million. Online peptide advertising increased 678% from 2022.

Meanwhile, the research pipeline continued moving. Retatrutide, a triple agonist targeting GLP-1, GIP, & glucagon receptors, entered late-stage clinical trials.

Orforglipron, an oral, non-peptide GLP-1 receptor agonist from Eli Lilly, advanced toward potential FDA approval. Though it remains much less effective than its injectable predecessors.

WADA says enough

In January 2022, the World Anti-Doping Agency added BPC-157 to its Prohibited List under category S0 (Non-Approved Substances). GHRPs (GHRP-2, GHRP-6, hexarelin, ipamorelin) were already banned under S2 (Peptide Hormones and Growth Factors).

FDA crackdown

In September 2023, the FDA placed 19 peptides in Category 2 meaning compounding pharmacies could no longer legally produce them. The stated rationale across these compounds included immunogenicity risk, peptide-related impurities, & insufficient human safety data.

Demand didn’t disappear. If anything, the restrictions amplified interest. Many turned to research chemical vendors and unregulated online suppliers. And so the peptide wild west was born.

Not without growing pains though. Enforcement escalated in June 2025 when the FDA raided Amino Asylum. More than 50 warning letters went to GLP-1 compounders a few months later and state-level enforcement followed. By March 2026, one of the biggest hubs, Peptide Sciences, voluntarily closed its doors.

The reclass

On February 27, 2026, HHS Secretary RFK, Jr. appeared on Joe Rogan hinting that he expects ~14 of the 19 previously restricted peptides to return to Category 1 status restoring the ability of licensed compounding pharmacies to produce them.

6 weeks later on April 15, 2026, the FDA made it official with a formal meeting scheduled for July 2026 where panelists will consider whether 12 peptides should be permitted for routine compounding.

2026 & beyond: Where we go from here

As of mid-2026, we’re sitting at the Peak of Inflated Expectations marked by the Hollywood GLP mismanagement look & the predatory TikTok affiliate culture.

Collectively, all of it has pushed expectations beyond what the evidence currently supports. And to be clear – the evidence is substantial by iteself.

So where do we go from here?

Like most technology curves, the correction is acute followed by a long-term stabilization.

The timeline forward is characterized by a few principles:

1. Real-world friction corrects the overshoot: Results are going to be bioindividualized & health context-dependent. Many will begin to discover that peptides amplify most lifestyle inputs rather than replace them. In other words, you can properly dose the MOTS-c all you want, but if diet isn’t dialed in, training is inconsistent, & sleep quality/circadian regulation is subpar, outcomes will fall short of expectations.

2. Maturing human data replaces hype with bioindividual precision: Expect to see much of Khavinson’s work replicated and even more mechanistic studies. Do not expect the RCTs to originate from the NIH, but instead from decentralized institutions/clinics running their own. Even the language shifts from generalized “peptides” to highly individualized, objective-driven interventions.

3. Oral / nasal delivery & commoditization strip away the mystique: The one thing standing in the way more than any other component for most is the fear of needles. A 2022 survey put that number at ~63% having at least some fear. Orforglipron-style molecules (oral + mass-manufacturable) transform GLP-1 therapy from an exclusive injectable to a widely accessible oral drug. This drives the most adoption and where we cross the chasm from early adopted crowd to gen pop adoption.

4. Regulatory stabilization prevents a deep trough: The RFK-led HHS reclassification (now formalized with a July 2026 FDA review) restores compounding access and pulls volume out of the gray market.

Beyond 2027, here’s what the Slope of Enlightenment & eventual Plateau of Productivity look like for each peptide category:

• GLPs: On the Slope, more large-scale outcome trials and decentralized data gathering clarify metabolic effects while microdosing/adjacent protocols mitigate side effects & muscle loss. By the Plateau, they sit as routine staples integrated into primary care and boringly effective lifestyle adjuncts.

• Healing peptides (BPC-157, TB-500/thymosins): The Slope brings targeted human RCTs and imaging data from decentralized, broscience style sources. This proves localized repair without systemic risks. On the Plateau, they become standard adjuncts in gut healing, sports medicine & post-surgical protocols.

• GH secretagogues: Maturing pharmacokinetic and safety studies on the Slope refine dosing windows & cortisol mitigation. At the Plateau, they stabilize as niche tools for GH deficiency cases, muscle loss in older adults, & GLP adjacent protocols.

• Bioregulators (Khavinson short peptides like Pinealon & Epitalon + GHK-Cu): Western replication trials on the Slope finally validate epigenetic gene regulation & oral bioavailability. By the Plateau, they emerge as foundational healthspan optimization tools for circadian rhythm regulation, skin, hair, thymus, & stress resilience.

• Nootropic peptides (Selank, Semax): The Slope brings clean cognitive and anti-anxiety trials detailing blood-brain-barrier penetration and neurotransmitter modulation. On the Plateau, they settle as targeted adjuncts for focus, recovery from stress, or mild neuroinflammation especially in older adults with early onset neurodegeneration.

• Melanocortins: Dose-response & long-term safety data on the Slope define targeted therapeutic windows for tanning, libido, & appetite with less of the old nausea worries. At the Plateau, they become staples at specialized med spas & peptide clinics. More accessibility, female adoption, & mobility enabled by nasal spray applications.

• Antimicrobial peptides (LL-37): The Slope sees microbiome and infection outcome studies proving selective pathogen control without dysbiosis. The Plateau integrates these as next-generation adjuncts for gut, skin, and chronic low-grade infections.

• Mitochondrial peptides (MOTS-c, SS-31): Early human energetics & fatigue trials on the Slope map vitality gains. By the Plateau, they anchor regenerative protocols for mitochondrial decline targeted for insulin/leptin sensitivity, chronic fatigue, or age-related vitality loss.

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Final word

Before we depart, here’s one practical takeaway to remember: peptides amplify inputs & will never replace the lifestyle boulders.

If the first century of our peptide timeline built the molecules, the next decade will build the infrastructure of sovereign decentralized testing, cleaner clinical evidence, & delivery innovation.

We’re cautiously optimistic as we continue our own research & spread the lessons learned from the research of other elite practitioners in the community.

In the meantime, steer clear of Peptide TikTok, study what’s presented here (much more to come), & stay elite. We’ll see you guys next week.

Your friend,
Phys

A younger dude recently came to me. Trouble falling asleep. Trouble staying asleep. Waking up around 2–3 AM every morning. After walking through his foundations: diet, bloods, gut function, daily routine including light environment, digital diet, movement, social habits and any acute/chronic stressors. Everything dialed in.

Having dealt with the same issue myself, I asked: “Do you wear a sleep tracker?”

“Yep.”

I told him to take it off for a month.

Three weeks later: “I’ve felt more refreshed this past week than I have in over 2 years.”

Turns out the research community already had a formal term for it: orthosomnia, where sleep tracker obsession itself disrupts sleep architecture increasing pre-sleep anxiety.

He’s not alone. People buy the Whoop or OURA to sleep better only to sleep worse because the device said so. The cycle repeats.

“So be ignorant…?”

Nope — it’s about learning to read the biologically built-in signals your body already provides.

Here are 12 proxies that replace performative tech with something more reliable: your own awareness.

I. The Morning Read (what your body tells you before you do anything)

#1: Sleep Quality → Morning Focus + Tolerance

Replaces: Oura/WHOOP/Apple Watch sleep scores

Can you sustain focus without a headache/brain fog for 30+ minutes upon waking? Does the guy chomping on his bagel with cream cheese in your ear not bother you (as much)? If yes to both, your glymphatic system cleared metabolic waste (beta-amyloid, tau proteins) overnight, cortisol awakening response rose on schedule, and excitatory glutamate isn’t lingering from incomplete NREM cycling. Some of the markers of restorative sleep.

#2: Caffeine Tolerance → Coffee Response Gauge

Replaces: Cortisol timing apps, adenosine receptor speculation

Do 2–3 cups of coffee feel like jet fuel? If they barely register or make you anxious, you’ve either: 1) saturated adenosine receptor tolerance or 2) your autonomic nervous system scale is habitually tipped towards the sympathetic side without enough parasympathetic tone.

#3: HRV / Autonomic Balance → Morning Wood / Bean

Replaces: HRV wearables

The single best free proxy for vascular and nervous system health that exists. We speak about this one at length here:

II: The Calibration Check (are your neurochemical signals functioning correctly?)

#4: Dopamine Sensitivity → Music Response

Replaces: Dopamine detox protocols

When you turn on a banger, does it hit like a mild drug?

Let this serve as an honest marker of intact mesolimbic reward signaling. If music feels flat, your D2 (dopamine) receptor density is downregulated & prolactin likely elevated from chronic overstimulation/digital anhedonic state of excess social media, stims, & gooning. The fix lies in deleting the low-cost dopamine vectors & activating the dopaminergic system via valuable accomplishment.

#5: Hormone Balance → Reply Guy Test

Replaces: Frequent testosterone/estrogen panels

If a reply guy on social media sends you into a tailspin, he’s entered into your OODA loop successfully (only you have the keys). There’s a good chance your androgen levels are outpacing estradiol’s modulatory role (generally a T/E2 or DHT/T imbalance). Or your inhibitory GABA tone is paired with an excess glutamate buildup. The combination of hormones and neurochemistry represents a nice proxy for fuse length.

Note: Biannual bloodwork remains a non-negotiable.

#6: Stress Resilience → Breath & RHR Awareness

Replaces: HRV-guided breathwork apps, stress scores

Can you bring a racing heart & spiraling thoughts under control with 5 slow, deep breaths? A direct test of vagal efferent tone and your capacity to upregulate parasympathetic output via the baroreflex.

III: The Functional Layer (what your body reveals through function)

#7: Body Composition → Mirror

Replaces: InBody, DEXA scans

Use a mirror & pair it with:

1. Visual references

   

2. Body fat estimation descriptions

I still recommend getting a baseline DEXA scan as early as possible, then every few years afterwards to monitor bone mineral density & visceral adipose tissue as you age. An example of what a typical read out provides below.

#8: Gut Health → Daily Poops

Replaces: GI-MAP, Viome, microbiome sequencing kits

Do you have a daily, well-formed bowel movement? Bonus points if around the same time of day. Daily poops are an easy proxy for a favorable gut microbial profile & fortified gut barrier integrity.

Added bonus: can you trust a fart?

#9: Energy / Metabolic Health → Post-Meal Vitality Check

Replaces: Continuous glucose monitors

Sustained energy post-meal reflects efficient glucose uptake & an adequate insulin/leptin response. Conversely, postprandial crashes point to insulin resistance, poor metabolic flexibility, or mitochondrial inefficiency.

#10: Immune Function → Acute Stress Recovery

Replaces: Inflammatory marker panels (i.e. CRP), immune “scores”

How fast do you bounce back from a hard training session, a bad restaurant meal, or a stressful stretch? If a minor stressor knocks you out for 2–3 days, you may have an elevated low-grade inflammation baseline, slow resolution of acute inflammation, or nutrient insufficiency limiting immune cell turnover. Resilience is the metric.

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IV: The Cognitive Output Layer (what your biology produced in terms of cognition & action)

#11: Screen Time → Daily Value Audit

Replaces: Screen time reports

Screen time has evolved into a virtually useless metric. We all live in the digital world and will continue to. At the end of the day, one thing matters: “What of value did I accomplish today?” You can create any daily value audit that works best for you, but one I like is conducting an analog (pen + notebook) version of the Daily Examen. This forces you to confront what you delivered to your future self, your family, & society.

Simple: Be still → Be grateful → Be reflective of what you got done today → Be authentic of what you fell short on → Be deliberate in what lies ahead tomorrow

#12: Cognitive Health → Memory Recall Speed

Replaces: Brain training apps, cognitive assessment tools

The inability to recall specific details from yesterday’s conversations suggests impaired hippocampal consolidation, which is often downstream of disrupted deep sleep, neuroinflammation, or inadequate acetylcholine precursor availability (choline + tyrosine + taurine + B-vitamins + DHA).

Final Word: Don’t Be Neurotic

The health space is dominated by a principle of being overquantified by the underqualified. Because of the over-quantification trend, we’ve quietly become addicted to the data and it’s come at a steep cost/

What were once useful tools are now symbols of performative self-improvement. The stress of optimization ironically created the very dysfunction most are trying to prevent. And often too afraid to openly admit.

The irony would be turning these proxies into a rigid checklist you obsess over.

The real goal here is building bioindividual interoception: the ability to perceive and accurately interpret your body’s internal signals. Higher interoceptive awareness consistently correlates with better emotional regulation, improved decision-making, & stronger health outcomes across time & space.

Your body gives off useful data and the best health tool you own is the skill of being able to listen to it. (free by the way)

Your friend,
Phys

Refer a friend

It’s neither your imagination nor another Reddit-induced symptom. The same molecule that sedates most is exciting your neurons through a receptor system few know of.

Here’s why that’s happening & a ranked protocol to fix it.

Contents:

• How Glycine Promotes Sleep

• Why Glycine Wires Some People Up

• The Four Factors Behind the Paradox

• The Protocol: Ranked by Priority & ROI

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How Glycine Promotes Sleep (When It Works)

Glycine is one of two inhibitory neurotransmitters in the central nervous system — GABA being the other. Its functions range from glutathione synthesis to bile acid conjugation to neurotransmission and is a big reason why you hear so much chatter on eating nose-to-tail in the social media space.

Glycine activates NMDA receptors triggering the thermoregulatory cascade that initiates natural sleep: peripheral vasodilation → drops core body temperature → shortens sleep onset latency.

In Yamadera et al. (2007), 3 g of glycine taken one hour before bedtime:

• Improved subjective sleep quality

  

• Shortened sleep onset

  

• Improved next-day cognitive performance

  

But unfortunately, there’s biochemical variation (many such cases).

The Paradox: Why Glycine Wires Some People

Glycine acts as an inhibitory neurotransmitter, but it also functions as a co-agonist with glutamate at the NMDA receptor’s glycine binding site.

By taking exogenous glycine, you saturate both the inhibitory glycine receptors & the NMDA co-agonist site. And the latter mechanism is how you start to activate glutamatergic excitation across the brain.

Zhang et al. (2014) showed this switch is dose-dependent & bidirectional:

• Low extracellular glycine → favors long-term NMDA depression → net inhibition + calmer brain

• Higher glycine → flips to long-term NMDA potentiation → strengthened excitatory synapses + heightened arousal

The same molecule that zonks one person out in 30 min leaves another staring at the ceiling at 2 AM with monkey brain, night sweats, & a heart rate that won’t drop below 75 bpm.

That’s the glycine paradox summed up. And where you fall on that spectrum comes down to four predisposing factors.

The Four Factors Behind the Paradox

1. Impaired Cellular Energy Metabolism (The Master Variable)

GABA & glycine normally inhibit neurons by opening chloride channels allowing chloride ions to flow in and create a calming negative charge. But this requires low intracellular chloride levels maintained by the KCC2 transporter.

KCC2 relies on a potassium gradient generated by the Na⁺/K⁺-ATPase pump, which consumes ATP to function properly. When ATP levels drop due to factors like B-vitamin deficiencies, thyroid/mitochondrial issues, or insulin resistance, the pump fails leading to chloride buildup inside neurons.

Opening the channels causes chloride to flow outward depolarizing the cell and flipping glycine (and potentially GABA) from inhibitory to excitatory.

This is why both creatine (increased phosphocreatine stores) & niacinamide (a direct NAD+ booster) can rescue glycine intolerance: it restores ATP → rebuilds the chloride gradient → flips the switch back to calm.

2. Elevated Glutamate Tone / GABA-Glutamate Imbalance

NMDA receptors need both glutamate and glycine to fire. If your glutamate tone is already elevated (anxiety, MSG in hyperpalatable foods, glutamine supps, neuroinflammation), glycine simply completes the circuit unbalancing your inhibitory-to-excitatory signaling.

Glutamine converts to glutamate in the brain via glutaminase. It’s a great tool for fortifying the gut barrier (especially for the elite athletes here), but it can easily be a hidden trigger. More on that later.

3. Genetic & Epigenetic Vulnerabilities

For those who’ve done genetic testing, certain variants tilt the scales toward excitation:

• GLRA1/GLRB: Weaker inhibitory glycine receptors.

• GlyT1/GlyT2: Slower glycine clearance, prolonging NMDA exposure.

• MTHFR: Impaired methylation and ATP production; glycine itself feeds into this loop.

• GAD1/GAD2: Poor glutamate-to-GABA conversion, especially with low B6.

4. Environmental & Lifestyle Factors

If your system is already wired for excitation (poor daylight exposure + bright evenings via blue heavy LEDs/screens + excessive nnEMF), bringing glycine into the picture floods NMDA sites & furthers excitatory signaling.

The Protocol: Ranked by Priority & ROI

The interventions below are ordered by mechanistic importance and expected return on investment. Start at the top and work down. Most will resolve the issue within the first three tiers.

Tier 1 — Immediate

1a. Reduce Dose & Adjust Timing

Drop from 3 g → 500 mg & titrate up by 500 mg increments every 3–5 days. Take glycine after dinner (2–3 hours before bed) rather than at bedtime giving time for the initial NMDA-mediated cortical arousal to subside.

Dose: Start at 500 mg, 2–3 hrs before bed. Titrate to tolerance. If 1 g still produces insomnia, move to intervention 1b.

1b. Switch Magnesium Form Away from Glycinate

Replace magnesium glycinate with a non-glycine form for your nighttime dose. Reserve glycinate for daytime if desired.

Forms (ranked):
➜ Magnesium acetyl-taurinate (200–400 mg Mg; taurine adds GABAergic support)
➜ Magnesium L-threonate (200 mg Mg; crosses BBB, supports synaptic Mg²⁺)
➜ Magnesium chloride (200–400 mg Mg; well-absorbed, no excitatory amino acids).

1c. Swap Isolated Glycine for Collagen Peptides

Thomas et al. (2023) showed that 15 g collagen peptides (providing ~3.5 g glycine) reduced nighttime awakenings by 27% without the core temperature changes seen with pure glycine.

Dose: 10–15 g collagen peptides (hydrolyzed, grass-fed bovine or wild-caught marine), 1 hr before bed, dissolved in liquid without food.

Tier 2 — Foundational (Weeks 1-4)

2a. Restore Cellular Energy Metabolism via B Vitamins + Creatine

Han et al. (2025) noted that subclinical deficiencies in B1, B2, B3, B6, folate, & B12 compromise neuronal energy metabolism and neurotransmitter synthesis sufficiently to produce insomnia, anxiety, and cognitive dysfunction.

Priority B vitamins:
➜ B3 (Niacinamide): 500 mg at bedtime.
➜ B1 (Thiamine): 100–300 mg benfotiamine or thiamine HCl. Rate-limiting for Krebs cycle.
➜ B2 (Riboflavin): 25–50 mg riboflavin-5'-phosphate. Supports electron transport chain.
➜ B6 (P5P): 25–50 mg. Cofactor for GAD enzyme (glutamate → GABA).
➜ B12: 500—750 mcg methylcobalamin or hydroxocobalamin. Check serum B12 on next bloods.
➜ B9 (5-MTHF): 400–800 mcg. Supports methylation.
➜ B7 (Biotin): 150 µg for first 100 g protein + every additional 50 g protein requires an extra 35 µg biotin.
Track intake via Cronometer, Microgram or any micronutrient tracking app.

2b. Optimize Electrolytes (Sodium, Potassium, Magnesium, Calcium)

Target a sodium-to-potassium ratio of ~1:2–3 by intake. The sad story of SAD (Standard American Diets) is inverted (high sodium + low potassium = cardiovascular issues).

Targets:
➜ Potassium: 3,500–6,000 mg/day (primarily from food)
➜ Sodium: 1,500–2,500 mg/day
➜ Magnesium: 800–1,200 mg/day (food + supplement, non-glycinate form at night)
➜ Calcium: 1,000—1,200 mg/day (food preferred)

2c. Eliminate Glutamine Supplementation & Reduce Dietary Glutamate

If you are supplementing L-glutamine for gut related use cases, trial a 2–4 week washout & assess sleep quality changes. Eliminate all hyperpalatable foods high in added glutamate.

Action: Discontinue L-glutamine. Or at least, prioritize around breakfast. Minimize MSG & hydrolyzed protein sources. Reassess after 2–4 weeks.

Tier 3 — Diagnostic + Environmental

3a. Order Targeted Bloodwork

Test. Don’t guess.

Priority labs on next bloodwork:
➜ Serum B12 + methylmalonic acid (functional B12 status)
➜ Full thyroid panel: TSH, free T3, free T4, reverse T3, TPO antibodies (thyroid dysfunction = impaired ATP)
➜ Fasting insulin + glucose (poor insulin sensitivity = impaired neuronal energy)
➜ Homocysteine (elevated = impaired methylation, B12/folate/B6 functional status)
➜ RBC magnesium (serum Mg is unreliable; RBC reflects intracellular stores)
➜ Serum ferritin (iron is cofactor for SHMT enzyme interconverting glycine)

Optional (if above is unrevealing):
➜ Organic acids test (OAT): screens for B vitamin functional deficiencies, mitochondrial dysfunction
➜ MTHFR / COMT / GAD1 genotyping: leverage if there's a pattern of paradoxical supplement responses

3b. Light & EMF Hygiene

Blue-light blockers post-sunset, dimming lights to <50 lux in the evening (incandescents), and minimizing social media time/digital exposure 45—60 min before bed can significantly reduce the excitatory load that glycine is being added on top of.

Actions:
➜ Blue-light blockers (red ones) after sunset
➜ Dim ambient light to <50 lux after 8 PM
➜ Device-free wind-down period 45—60 min before bed
➜ Kill nnEMF sources (phone/router)

Tier 4 — GABAergic Support (Add as Needed)

4a. Add GABAergic Compounds to Counterbalance NMDA Activity

Evidence-based GABAergic agents (ranked by strength of evidence):

Amino acids & related compounds:
➜ Taurine (3–5 g): Activates GABA-A & glycine receptors. Calms neural excitability without binding NMDA.
➜ L-Theanine (400–800 mg): Upregulates brain GABA. Structurally similar to glutamate so competitively inhibits glutamate binding at AMPA receptors.
➜ Myo-inositol (2–4 g): Involved in GABA-A receptor function via phosphoinositide signaling. Evidence for anxiolytic & sleep-promoting effects at higher doses.

Herbal GABAergics:
➜ Lemon balm (300–600 mg extract): Inhibits GABA-transaminase (the enzyme that degrades GABA) raising synaptic GABA levels. Reduced insomnia by 42% as standalone in one trial.
➜ Passionflower (250–500 mg extract): GABA-A positive allosteric modulator via chrysin and other flavonoids. Comparable to oxazepam (30 mg) for generalized anxiety in one RCT.
➜ Valerian root (300–600 mg extract): Contains valerenic acid, a GABA-A positive modulator.
➜ Chamomile (200–400 mg extract): Apigenin binds GABA-A benzodiazepine site with moderate affinity.
➜ Magnolia bark (200–400 mg): Contains honokiol & magnolol, potent GABA-A positive allosteric modulators with anxiolytic & sedative properties.
➜ Lavender/Bergamot (aromatherapy): Modulates voltage-dependent calcium channels and GABA-A receptors.
➜ Baikal Skullcap (250–500 mg): Baicalein & baicalin compounds modify the GABA-A receptors

Glycine Insomnia: Step-Through Protocol

SUMMARIZED

Alright that’s a wrap for this week. Sleep deeply.

Your friend,
Phys

Brooke opens up the presentation with a quote from a name that may look familiar.

Five years prior in 2013, Brooke co-founded Intervene Immune alongside Greg Fahy, a cryobiologist and the leading researcher of what’s become the now popular TRIIM Trial (Thymus Regeneration, Immunorestoration, and Insulin Mitigation).

As we await the results of this trial, the strongest evidence we’ve seen yet supporting the thymic-longevity thesis just landed in Nature.

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What We Used to Believe

The way the medical textbooks are written makes it appear pretty straightforward. The thymus was a childhood organ. It matured T cells. It built the immune arsenal. Then it shrank into an inconsequential lump of fat by midlife.

It was the accepted view for decades. Until 2023, when researchers at Massachusetts General Hospital published a huge finding: adults who had their thymus surgically removed had significantly higher rates of death, cancer, & autoimmune disease.

The Study

Researchers from Harvard, Maastricht University, & Aarhus University analyzed over 27k adults across two major prospective cohorts: the National Lung Screening Trial (NLST, n = 25,031) & the Framingham Heart Study (FHS, n = 2,581).

They built a deep learning system trained on thousands of CT scans to score “thymic health” quantifying how much functional thymic tissue remained versus fatty degeneration. Then they tracked outcomes over 12 years.

The Findings

1. High thymic health = dramatically lower mortality.

In the NLST, those with the highest thymic health scores had an ~50% reduction in risk of death from any cause compared to those with the lowest scores.

In the FHS, we get an even stronger effect. High thymic health was associated with a 76% lower risk of all-cause death.

Each step up in thymic health also corresponded to progressively lower mortality.

2. Lower cancer incidence and cancer-specific mortality.

Individuals with high thymic health were 36% less likely to develop lung cancer.

The high thymic health subjects also had ~50% less likely to die from it.

As the thymus involutes, two things happen simultaneously:

1. Naïve T cell output drops constricting the T cell receptor (TCR) arsenal. Fewer unique T cells = less defense to recognize novel tumor antigens. As we get older, age-related mutations produce tumor-specific neo-antigens and the naïve T cell pool fails to recognize them (Wang et al., 2020).

2. The involuted thymus shifts its output ratio toward regulatory T cells over effector T cells. More regulatory ones suppress anti-tumor immune responses. Senescent T cells upregulate PD-1 (programmed death 1) expression further enhancing the PD-1/PD-L1 axis that lets cancer cells evade destruction.

Palmer et al. (2018) predicted similarly: declining T cell output from thymic involution meant an age-related rise in cancer incidence. Across 25k+ people, they saw all forms of cancer mortality were significantly lower in the high thymic health group.

3. Cardiovascular disease risk dropped dramatically.

In the NLST, cardiovascular mortality was 63% lower in the high thymic health group.

In the FHS, it was 92% lower.

Subjects with high thymic health also had a 74% lower cumulative incidence of cardiovascular events like myocardial infarction, heart failure, & cerebral embolism.

Atherosclerosis is an immune-inflammatory disease so T cells are key to its progression:

Thymic output declines → the body compensates by cloning existing T cells rather than producing new ones → drives the accumulation of senescent T cells (shortened telomeres, restricted receptor diversity, & pro-inflammatory) → more pro-inflammatory cytokines → more destabilization of arterial plaques.

Thymic dysfunction also shifts the balance of T cell subsets meaning fewer defensive regulatory T cells & more pro-inflammatory Th1/Th17 cells.

4. The effect extended across most disease categories.

Beyond cancer & CVD, those with higher thymic health were less likely to die from:

• Pulmonary disease mortality: 61% lower for high thymic health

• Endocrine, metabolic, & nutritional disease mortality: 68% lower

• Digestive disease mortality (liver, gallbladder, pancreas): 54% lower

Thomas et al. (2020) showed that thymic involution has a dual-pathway model driving both immunosenescence (reduced immune competence) & inflammaging (chronic sterile inflammation).

T cells do more than fight infections. They recognize & eliminate senescent cells. So when thymic output drops, this clearance function fails, & the aging cell burden grows across every tissue.

5. Chronic inflammation and metabolic dysfunction tracked with thymic decay.

When researchers analyzed blood inflammatory proteins in the FHS, 16 of 68 tested proteins were negatively correlated with thymic health. The list included IL-6, IL-18, VEGFA, HGF, and several CXCL chemokines, which are all major drivers of systemic inflammation, atherosclerosis, & cancer progression.

The same trends held true for cardiometabolic markers. Higher HDL cholesterol was positively correlated with better thymic health. Triglycerides, fasting glucose, & blood pressure were all negatively associated.

Another reason to keep a close eye on the trig/HDL ratio over time.

It shouldn’t come as a surprise, but obesity accelerates thymic involution (especially visceral fat tissue):

More visceral fat (inflammatory “organ”) → increased chronic inflammation accelerates thymic decay → thymic decay reduces immune competence → allows aging cell accumulation → senescent cells produce more inflammation → cycle compounds with age.

Promising Thymus Regeneration Paths

In September 2023, ARPA-H announced funding for a dedicated Thymus Rejuvenation program.

But the private sector is moving faster as multiple startups are now directly targeting thymus regeneration:

Intervene Immune → Brooke & Fahy’s company is furthest along clinically. Their TRIIM-X trial uses personalized combos of growth hormone, DHEA, & metformin to regrow thymic tissue in adults using already-approved drugs. So far interim results look promising.

Thymmune → Engineering functional thymus tissue from stem cells building replacements rather than regenerating what’s left.

TECregen → Emerged with $12.6M in seed funding to selectively regenerate thymic tissue using ligand engineering without the systemic toxicity that’s plagued growth factor approaches.

Tolerance Bio → $20.2M funded. Targeting immune tolerance through the thymus. Focused on autoimmune disease rather than pure regeneration.

Repair Biotechnologies → Developing gene & protein therapies to reverse thymic atrophy directly.

Where We Go From Here

An obvious question remains: “What can we do about it now?”

First, bioindividuality will remain key in the advancement of the therapeutic efforts moving forward. One of the best voices in our space summarized this:

And Dr. Bakri isn’t the only one paying attention:

We’ve had decades of asking why cancer patients fail immunotherapy, while the better question may have been whether their immune system was ever equipped for the fight to begin with.

Expect at least 1-2 regeneration protocols developed in 2026. As always, we’ll stay tuned & continue our research efforts on what promising regeneration protocols might look like in the future. More to come.

See you guys next week,
Phys

The one you’ll find in 90%+ of supplements on the shelf/Amazon is ubiquinone (marketed as CoQ10).

Ubiquinol is the reduced form. The type your cells use to scavenge free radicals, stabilize membranes, & protect LDL particles from the oxidation.

Now we have finally have a pair of studies released this month showing the efficacy (& superiority) of ubiquinol like we’ve never seen before.

Contents:

• The Study

• Findings

• The Bioavailability Gap

• How Ubiquinol Works

• Ubiquinol’s Cardiometabolic Benefits

• Practical Takeaways

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The Study

Researchers in Bangkok published a pilot RCT looking at what happens when you give adults 100 mg/day of ubiquinol for 12 weeks and studied the shifts in oxLDL as the primary outcome.

Study Snapshot

Who were the subjects?

• 20 Thai adults with prediabetes (fasting blood glucose = 100–125 mg/dL) → chosen for a distressed CoQ10 system & upstream mitochondrial dysfunction

• Ages 18–60

What did researchers study?

Using a randomized, double-blind, placebo-controlled design:

• Ubiquinol group (n = 10): 100 mg/day ubiquinol (≥ 96%) in MCT oil

• Placebo group (n = 10): Identical capsule with MCT oil only

• Duration: 12 weeks

• One capsule daily after first meal

What was measured?

• Plasma oxLDL at baseline & week 12

• Fasting glucose, liver enzymes, kidney function, CBC

Findings

Ubiquinol significantly reduced oxLDL within the treatment group.

The ubiquinol group saw oxLDL drop from 53.16 to 50.16 U/L over 12 weeks (p = 0.049). The placebo group showed no significant change (51.65 → 49.28, p = 0.237).

Why oxLDL?

LDL-C alone isn’t an efficient screening test for heart disease.

Oxidized LDL (oxLDL) is what happens when a normal LDL particle undergoes harm by reactive oxygen species.

The mechanism: LDL gets oxidized → becomes pro-inflammatory & pro-atherogenic → penetrates the arterial wall → gets engulfed by macrophages → forms foam cells → initiates plaque buildup

LDL-C tells you how much cholesterol is circulating. oxLDL tells you how much of it has already been damaged and is actively contributing to arterial injury.

The Bioavailability Gap

In the same week, we got pharmacokinetic proof ubiquinol is superior to ubiquinone.

A randomized, double-blind crossover study (Mei et al., 2026) published in March 2026 compared the two forms head-to-head in 12 healthy adults aged 45–65.

Each subject got a single equivalent dose of both formulations (240 mg), separated by a 14-day washout. Plasma CoQ10 was tracked for 48 hours.

The results:

• Peak plasma concentration (Cmax): ubiquinol was 2.2x higher than ubiquinone

• Total plasma exposure over time (AUC₀₋ₜ): ubiquinol was 2.0x higher

• Total systemic exposure extrapolated to infinity (AUC₀₋∞): ubiquinol was 3.4x higher

That final number matters most for long-term supplementation. It represents total bioavailability or what reaches systemic circulation.

How Ubiquinol Works

Ubiquinol provides LDL protection via three pathways:

1. Direct radical scavenging: Donates hydrogen atoms to neutralize lipid peroxyl & alkoxyl radicals. This interrupts the chain reaction of lipid peroxidation — the process converting normal LDL into oxLDL.

2. Antioxidant recycling: Regenerates other lipid-soluble antioxidants like vitamin E. This amplifies the total antioxidant capacity beyond what ubiquinol alone provides.

3. Mitochondrial stabilization: Ubiquinol is embedded in the electron transport chain. When mitochondrial function is preserved, less reactive oxygen species leak out. Less ROS = less LDL oxidation upstream.

Ubiquinol’s Broader Cardiometabolic Benefits

Some more of what the data supports:

Endothelial Function

A randomized, double-blind trial (Sabbatinelli et al., 2020) gave dyslipidemic adults 100 & 200 mg/day of ubiquinol for 8 weeks. Both doses significantly improved flow-mediated dilation, a direct measure of how well your blood vessels dilate & constrict.

Blood Pressure

A meta-analysis of 45 RCTs (Karimi et al., 2025) found that CoQ10 significantly reduced systolic blood pressure –3.5 mmHg on average.

Glycemic Control

A newly released double-blind, placebo-controlled trial (Palakornkitti et al., 2026) showed 20 adults given 100 mg/day ubiquinol for 12 weeks significantly improved insulin sensitivity.

Cardiovascular Mortality

The KiSel-10 trial (Alehagen et al., 2013), a five-year placebo-controlled study of 440 elderly adults, combined 200 mg CoQ10 with 200 µg selenium daily. The treatment group had a ~50% relative reduction in cardiovascular mortality vs. placebo (5.9% vs. 12.6%).

Heart Failure

The Q-SYMBIO trial (Mortensen et al. 2014) demonstrated that 420 patients in a 2-year trial given 300 mg CoQ10 daily reduced cardiac and all-cause mortality by 44% & 42%, respectively.

Antioxidant Capacity

A randomized, double-blinded, placebo-controlled trial (Ho et al., 2020) gave 31 healthy college athletes 300 mg of ubiquinone/day for 12 weeks. The treatment group had improved insulin sensitivity and increased total antioxidant capacity.

Statin-Induced CoQ10 Depletion

***CoQ10 is especially important if you’re running a statin*** (topic for another time)

Statins inhibit HMG-CoA reductase — the same pathway that produces CoQ10. Inhibit this enzyme and you start to deplete CoQ10 levels and impair mitochondrial energy production in muscles and the heart.

We have a few clear cases where CoQ10 taken adjacent to statins showed strong benefits:

1. Caso et al. (2007): 100 mg/day of CoQ10 across 32 hyperlipidemic patients for 30 days significantly reduced muscle pain by 40%, compared to Vit E alone, in patients treated with statins.

   

2. Fedacko et al. (2013): 60 patients supplementing with CoQ10 at 200 mg/day for three months significantly improved muscle pain & weakness in patients with statin-associated myopathy.

3. Skarlovnik et al. (2014): CoQ10 at 100 mg/day for 30 days significantly reduced statin-related muscle symptoms in ~75% of patients.

Practical Takeaways

1. If you’re taking CoQ10, check the form.

Ubiquinone/CoQ10 (the oxidized form) is cheaper & more common, but ubiquinol (the reduced form) has superior bioavailability & higher plasma concentrations after ingesting. If you’re over 40 or if you have any degree of metabolic dysfunction, your ability to convert ubiquinone → ubiquinol declines. Opt for ubiquinol.

2. Start at 100 mg/day.

Depending on cardiometabolic condition & antioxidant status, most will find 100–300 mg/day sufficient. If taking 200+ mg/day, split into two doses (morning + afternoon).

3. Always take it with fat. Morning or lunch is ideal.

Highest ROI lever. CoQ10 is fat-soluble and requires dietary fats for absorption. Without fat, bioavailability drops by ~75%. Take it with eggs, avocado, Brazil nuts, EVOO, or fatty fish (i.e. wild salmon, sardines). Morning or early afternoon is preferred because CoQ10 supports ATP production and some people have mild energizing effects that can interfere with sleep if taken late. Peak plasma concentration hits 6–8 hours post-dose, so morning intake aligns peak levels with daytime energy demand.

4. If you’re on a statin, ubiquinol is essential.

100–200 mg/day of ubiquinol taken at the opposite end of the day from your statin (morning vs. evening or vice versa) helps restore what the drug strips out. The objective is to mitigate its collateral damage on the mitochondria.

5. oxLDL deserves a spot on your biomarker radar.

oxLDL provides a better indicator on CV risk than LDL-C alone. Well worth the addition especially if older or you have some level of mitochondrial dysfunction you want to investigate.

6. Amplify ubiquinol’s effects.

Two synergistic micronutrients to pair with:

➜ Selenium (200 µg/day) is the cofactor for thioredoxin reductase, which is the enzyme that recycles oxidized CoQ10 back into active ubiquinol. Without adequate selenium, your body can’t efficiently reactivate the CoQ10 you’re supplementing.

➜ Vitamin E (200–400 IU mixed) forms a synergistic antioxidant loop with ubiquinol in the lipid membrane. Vitamin E handles initial chain-breaking during lipid peroxidation. Ubiquinol regenerates it back to its active form.

Aim to fulfill these needs through a food first approach (i.e. sardines, wild salmon, pasture-raised eggs, mackerel).

Ubiquinol sits at the intersection of three crucial cardiometabolic areas:

1. the oxidative state of lipoproteins,

2. the efficiency of mitochondrial antioxidant systems,

3. the ATP generation of high-energy tissues like cardiac/skeletal muscles.

If elite cardiometabolic health is in your set of long-term health objectives, ubiquinol may be worth a look.

Stay after it,
Phys

Cook your carbs, chill them overnight, and a sizeable fraction of their starch recrystallizes into a structure your digestive enzymes can’t break down. Instead, it travels to your gut feeding beneficial bacteria with metabolic benefits: enhanced insulin response, reduced visceral fat, & better liver markers.

It’s a simple combo: A fridge and a little bit of patience.

Contents:

• What Happens When Starch Retrogrades

• The Birth of Resistant Starch Type 3 (RS3)

• The Metabolic Outcomes

• Retrogradation Protocol

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What Happens When Starch Retrogrades

Raw starch is made of two polymers: amylose (linear chains) and amylopectin (branched chains). Cooking breaks apart these crystalline structures through gelatinization: granules swell → organization collapses → the starch becomes accessible to digestive enzymes. This is why freshly cooked carbs produce steeper glucose spikes.

When gelatinized starch cools, the disaggregated polymers reassemble into new, partially ordered crystalline structures. They wrap into tight double helices, which are denser, more compact, and resistant to the enzymes that normally break starch into glucose. This reassembly is called retrogradation.

Two details that matter for application:

1. 24 hours at 40°F = minimum threshold. Amylose retrogrades rapidly within the first 12 hours. Amylopectin retrogrades more gradually over days. The full 24-hour chill maximizes resistant starch (RS3) yield across rice, spuds, & pasta.

2. Gentle reheating doesn’t undo it. Retrograded structures hold below ~265°F covering microwaving, stovetop warming, and standard oven/air fryer reheating. You can chill your rice overnight, warm it the next morning, & still retain the full metabolic advantage.

The Birth of Resistant Starch Type 3 (RS3)

Resistant starch exists in five forms. RS3 (retrograded starch) is the only type you can produce in your own kitchen from foods you already eat.

Once formed, RS3 behaves like dietary fiber. It passes through your stomach and small intestine intact arriving in your colon where trillions of bacteria ferment it into beneficial metabolites.

Sonia et al. (2015) showed that cooked white rice cooled at 4°C for 24 hours then reheated had a 158% increase in RS containing 1.65 g RS per 100 g vs. just 0.64 g without cooling.

One more lever worth knowing: multiple heat-cool cycles increase RS3 content further. Each round of retrogradation adds another layer of enzyme-resistant crystalline structure. Batch-cook Sunday → refrigerate → reheat portions through the week = the carbs get more metabolically favorable with each cycle.

The Metabolic Outcomes

Weight Loss & Visceral Fat Reduction

Li et al. (2024) gave 37 overweight participants received 40 g/day of resistant starch (or a placebo) alongside isoenergetic balanced diets for 8 weeks.

The RS group lost an average of 6.2 lb and had significant reductions in visceral fat levels, total fat mass.

Pro-inflammatory markers (TNF-α & IL-1β) & liver enzymes (ALT/AST) also improved significantly.

How it works: RS intake → ↑ beneficial gut bacteria → altered bile acid profiles + reduced intestinal inflammation + inhibited lipid absorption → weight loss/metabolic optimization

Blood Sugar Control Across Populations

Strozyk et al. (2022) tested cooled rice (39°F for 24 hours, then reheated) against freshly cooked rice in 32 patients with type 1 diabetes. The area under the glycemic curve dropped by 60% with the cooled rice meal and peak glucose increase fell from 70 → 49 mg/dL.

Gut Health & the Butyrate Connection

When RS3 reaches the colon, resident bacteria ferment it into short-chain fatty acids (SCFAs) → primarily butyrate, along with acetate & propionate. Each plays a distinct role:

1. Butyrate = the preferred energy substrate for colonocytes (the cells lining your colon) maintaining gut barrier integrity & reducing intestinal permeability.

2. Propionate = regulates lipid metabolism in the liver.

3. Acetate = enters systemic circulation and influences appetite signaling & fat oxidation.

Resistant starch also stimulates the release of GLP-1 & PYY by SCFA binding to fatty-acid receptors on colonocytes. GLP-1 enhances insulin sensitivity and slows gastric emptying. PYY suppresses appetite.

Retrogradation Protocol

The 3 Rules

Rule 1: Cook fully, then cool for a minimum of 24 hours at 39°F (standard refrigerator temperature). Amylose retrogrades rapidly in the first 12 hours, but 24 hours at 39°F produces the highest RS3 yields across rice, potato, & pasta.

Rule 2: You can reheat gently, but stay below 130°C. Standard microwave reheating, stovetop warming, & oven temperatures up to about 130°C preserve retrograded RS3 structures.

Rule 3: Batch-cook & cycle. If you’re ambitious, multiple cook-cool cycles increase RS3 content with each round. So if you cook a large batch on Sunday, refrigerate, & reheat portions through the week, each cooling cycle reforms additional crystalline structures that resist digestion.

A Simple Meal-Prep System

Sunday Meal Prep Day: Cook a large batch of sweet/white potatoes (boiled/baked), rice, or pasta with your protein & seasonal vegetable source. Let your carb sources cool to room temp (~30 minutes), then transfer to glass containers & refrigerate (38-40°F).

What Covers My Monday–Thursday Meals:

• Breakfast: Overnight oats (naturally retrograded) with whey, fruit (berries, apple, banana), peanut butter powder, Ceylon cinnamon

• Lunch: Salad/slop bowl of your choice with protein source (90/10 grass-fed beef, chicken thighs/breasts, albacore tuna), cooked & cooled potatoes, veggie sources, EVOO + apple cider vinegar dressing

• Dinner: Protein source (wild-caught salmon/cod/shrimp, 90/10 grass-fed beef, chicken thighs/breasts), cooked & cooled rice (can reheat for 2 minutes) with cooked seasonal vegetables (brussels sprouts, broccoli, squash), splash of apple cider vinegar

Two Multipliers Worth Adding

Two simple additions to multiply the retrograded starch effect.

Vinegar

Leeman et al. (2005) tested four potato meal combinations in 13 healthy subjects. Cold-stored potatoes alone reduced the glycemic index by 26% vs. freshly boiled. When served with olive oil & white vinegar, they reduced glycemic index (GI) by 43%.

Östman et al. (2005) showed vinegar added to a bread meal reduced the GI by 36% and increased subjective satiety scores.

This works through acetic acid delaying gastric emptying → slowing the rate of food leaving your stomach → flattening the glucose curve further.

Practical dose: 1–2 tablespoons of vinegar (apple cider or white wine) per carb-dense meal. As a dressing or mixed into the dish.

Fiber

Soluble & insoluble fiber alongside retrograded starch further slows digestion. When a preceding meal is rich in dietary fiber, the glycemic response to the next starchy meal is also lower.

Practical dose: Pair retrograded starches with non-starchy vegetables. An additional lever = adding 1—2 tbsp psyllium husk fiber before meals.

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The food you eat and the structure it arrives in are two different variables. Retrogradation lets you optimize the second without changing the first.

Same rice. Same oats. Same potato. Same pasta. Much different metabolic outcome.

About as high efficiency as a metabolic “hack” gets. Use wisely, friends.

We’ll see you guys next week,
Phys