He’s a biochemist and professor at University College London who studies mitochondria for a living. Author of Power, Sex, Suicide and The Vital Question. Two of the most influential books ever written on how mitochondria power complex life, why they control aging, and what happens when they fail.

And when asked why he doesn’t take supplements, his answer is characteristically sharp:

“So if you’re thinking about taking supplements or whatever it may be, you’ve got to think. What are the long-term consequences of doing this? We don’t really have any good information on how that’s going to work out in the long run. And you don’t know what you’re missing. So that’s why I don’t do it personally.”

The argument that follows (laid out in a tweet that did 34,000 views) is one of the cleanest cases against supplementation I’ve read:

Free radicals aren’t cellular garbage. They’re signals. When mitochondria run into metabolic stress, those free radicals alter transcription factors in the nucleus. They tell the cell what to do next: build fresh mitochondria, activate its own antioxidant defenses, or trigger apoptosis if the damage is beyond repair.

Flood the system with antioxidant supplements and you mute that signal. The cell goes blind to its own internal state.

And there’s a second problem. Researcher Gustavo Barja traced most free radical leakage to one specific subunit inside Complex I, out of more than 40 subunits in that single complex. Free radicals leak directly into the space right next to mitochondrial DNA. There are tens of thousands of complexes per mitochondrion. Hundreds of mitochondria per cell. Roughly 50 trillion cells in the body. Hitting that exact site with enough antioxidant concentration is close to impossible.

Antioxidant supplements don’t fail only because they mute a signal. They fail because the target is unreachable.

You cannot supplement your way out of a systems problem.

I agree with nearly every word of this.

And I take supplements. Targeted ones. Based on data.

Seven organic acid tests. Four of them post-workout. Dozens of mitochondrial compounds tested. Everything compared against blood lactate.

Chris Masterjohn, who holds a PhD in nutritional sciences and has spent his career studying how nutrients interact with metabolism, put it best: “This is, on the one hand, very wise, yet on the other hand rather silly at the same time.” Lane is right that mitochondrial dysfunction is not one thing and throwing the same supplement at everyone is crazy. But mitochondrial dysfunction is in fact hundreds of things. And most of those hundreds of things have nutritional implications.

Because here’s what Lane’s argument misses. And it’s the thing that changes everything.

Most people test wrong. That includes the researchers.

Everyone tests at rest. Fasted. First thing in the morning. The assumption is that a rested baseline reveals dysfunction.

It doesn’t.

You don’t break when everything is running smoothly. You break under load. When you exercise. When you’re stressed. When demand exceeds capacity. Basically, when you get symptoms.

Only when someone is severely compromised does ordinary life break them. For everyone else, the stress test reveals the truth.

Doctors understand this intuitively. They do cardiac stress tests. Treadmill tests. They know a resting ECG misses what a loaded ECG catches. But nobody (not one person I can find) is doing the metabolic equivalent. Nobody is running an organic acid test post-workout to see how energy metabolism actually performs under stress.

Worse, the research Lane draws on is almost entirely in vitro. Isolated mitochondria. Cell cultures. Mechanistic studies showing that free radicals activate transcription factors and antioxidants block that activation.

This is good science. It establishes mechanism.

But in vivo, the picture changes a lot.

Most animal studies show that things which protect against stressors extend lifespan, not shorten it. Caloric restriction (basically just not being fat) reduces mitochondrial free radical generation at Complex I and lowers oxidative damage to mtDNA. That’s Barja’s own work. The same Barja who showed antioxidants can’t reach the target site.

The mitochondrial hormesis model (free radical signal → stress response → protective gene expression) requires the mitochondria to be capable of mounting that response.

If the mitochondria are dysfunctional, the signal never triggers adaptation. It just creates damage.

A healthy mitochondrion exposed to oxidative stress upregulates its defenses. A deficient mitochondrion exposed to the same stress degrades.

The difference between the two is whether the cofactors are present.

This is the gap. And it’s where my seven OATs come in.

Next I’m discussing:

• what your mitochondria actually need to function

• my specific mitochondrial bottleneck (and how I found and addressed it)

• 2 different classes of antioxidants (and which to focus on)

• the problem with mitochondrial research (what researchers are overlooking)

• what most people are actually lacking (it’s not antioxidants)

• what to do about mitochondrial function (as well as proper testing)

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I ran four stool tests across ten months that say the opposite.

What I found was worse than fiber intolerance. It was fiber creating problems that didn’t exist before. Pathogens appearing in a clean gut. A 12,000-fold increase in one bacterium. Immune exhaustion. A gut barrier that got worse the more fiber I ate.

And I had zero symptoms. No bloating. No diarrhea. Ghost wipe poops the whole time. If I hadn’t tested, I would have told you fiber was working perfectly.

This is not a post about why fiber is bad. It’s about why the advice to “just eat more fiber” is incomplete to the point of being dangerous. If you’re the kind of person who wants simple answers, you won’t find them here. If you want to understand what actually happens inside a human colon when you change one variable at a time, keep reading.

I’m going to walk you through four GI-MAPs, four diets, and the exact data that changed how I think about gut health forever. Here’s what I found.

The Four Tests

I tracked every pathogen, every commensal, every short-chain fatty acid, and every barrier marker through four different diets: no fiber, no fiber plus thymoquinone, high mixed fiber, and pure soluble fiber with thymoquinone.

Milk Diet (October 2025)

Five liters of milk a day. Thirty days. Essentially zero fiber. No supplements. No antimicrobials.

This wasn’t a gut protocol. It was a terrain experiment. If fixing digestion, lowering inflammation, and sealing the barrier mattered more than killing pathogens, a zero-fiber diet should prove it.

Inflammation hit the best numbers of the entire series. Calprotectin was 16. Zonulin was 95.5. The gut barrier was intact. Secretory IgA was elevated at 3519, suggesting active immune engagement.

But pathogens were everywhere. Enterococcus faecalis at 2.29 million. Enterococcus faecium at 2.82 million. Staphylococcus aureus at 5,360. Streptococcus at 39,900. Bacillus at 19.9 million. Citrobacter freundii at 630 million. Fusobacterium at 838 million. Escherichia at 10.3 billion.

Milk fixed the plumbing. It did lower some pathogens, but increased others. In general, I was still very happy with the results.

After Thymoquinone (June 2026)

One hundred milligrams of thymoquinone per day. Low fiber (around 5-10g daily). No other supplements.

This was a scorched-earth event. Firmicutes dropped from 815 billion to 7.65 billion, below the reference range. Bacteroidetes dropped from 1.7 trillion to 308 billion, also below range. The F:B ratio hit 0.02.

The pathogens got hit harder. Enterococcus faecalis went undetectable. Enterococcus faecium went undetectable. Staphylococcus aureus went undetectable. Citrobacter freundii went undetectable. Pseudomonas was undetectable and always had been. Fusobacterium dropped from 838 million to 323,000. Bacillus fell from 19.9 million to 249,000.

Two issues remained. Citrobacter spp. (not freundii) appeared at 1.17 billion. Streptococcus sat at 4,640. Zonulin crept to 184.7, slightly elevated. sIgA was 2138, still high but coming down.

This was some of the best results I’ve ever gotten. Almost complete eradication of every single pathogen I had. Not perfect, but pretty damn close.

Bean Diet (July 2026)

After seeing my tanked Firmicutes and Bacteroides, I thought this would be a prime time do mega dose fiber. So I consumed 50g of fiber daily from 500g of cooked beans daily. No supplements.

This is where the experiment gets interesting… and where the data stops being free.

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And boy, did it not disappoint.

I’m currently busy with a bunch of “ATP boosting”, “mitochondrial enhancement” supplement series.

It started with PQQ → mitoQ → thymoquinone → mitoQ + methylene blue. The next one is 5-amino-1MQ. The samples are already sent, so just waiting for the results.

Instead of recapping from the start, I’m starting from mitoQ, because it connects to this last test.

After a post-workout test as a control (no supplements), it was clear that I had some bottleneck and wasn’t recycling NADH fast enough back into NAD. This lead to a buildup of markers like L- and D-lactate, beta-hydroxybutyrate (BHB), alpha-hydroxybutyrate, etc.

The nutrient that was flagged as possibly low was CoQ10. I decided to go with mitoQ because it concentrates 1000x better in the mitochondria (where you want it) than regular CoQ10. This isn’t an absorption issue; it’s an accumulation benefit.

After using 20mg of mitoQ I thought my metabolic problems were solved.

Pyruvate:lactate ratio was clean, which matters because lactate accumulation is the fingerprint of NADH piling up faster than the cell can recycle it back to NAD+. When that ratio looks good, it means your mitochondria are running efficiently, PDH is engaged, and the Krebs cycle isn’t backed up.

After mitoQ, I ran out and used thymoquinone at 100mg (a relatively high dose). Quinones, like thymoquinone, has been shown to enhance NADH → NAD recycling.

The Crash

Succinic acid came back at 3.4x the upper limit. But fumaric acid, its own downstream product, was undetectable.

This is a textbook signature of a blocked enzyme: succinate dehydrogenase (SDH) had stopped converting succinate to fumarate.

Aconitase, a few steps earlier in the same cycle, showed the same pattern → cis-aconitic acid normal-to-high, isocitrate undetectable.

They share the iron-sulfur cluster, which is sensitive to oxidative stress, which “deactivates” it. When the enzyme becomes “deactivated”, the Kreb cycle doesn’t flow as it should and ATP production drops and this can create dysfunction that will upregulate compensatory pathways to help produce ATP.

My best explanation: thymoquinone can accept two electrons cleanly and become thymohydroquinone, a genuine antioxidant, or take just one, forming an unstable semiquinone radical that dumps its spare electron onto oxygen instead, generating superoxide. Iron-sulfur clusters are exactly what superoxide goes after.

The Question

I wondered: if I add MitoQ (which I hadn’t used during the thymoquinone test) plus methylene blue (MB), a redox cycler that works in both the mitochondria AND the cytosol, would that offset the SDH crash? And could it beat my previous 20mg MitoQ baseline?

The experiment: MB 25mg + MitoQ 10mg, still on 100mg thymoquinone.

What’s Coming

Here’s where it gets good. I’ll discuss:

• The Krebs cycle (in the mitochondria) effects

• Why working in two cellular compartments beat MitoQ alone at double the dose

• The estrogen numbers, including a metabolite shift with real antiproliferative properties

• The MAO-A surprise that rules out a serotonin syndrome concern

• The dose line that separates this from “nootropic” MB

Paid subscribers get the full data and mechanism below. Free subscribers, this is a good place to hit subscribe.

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You’ve done the $300 IV drip, lying there for ninety minutes while someone in scrubs told you it was “basically liquid youth.”

You’ve got the sublingual tablets sitting in your cabinet, half-used, because you forgot to take them for three days straight and gave up.

And you still crash at 2pm. You still wake up at 3am and stare at the ceiling. You still feel, if we’re being honest, exactly the same as you did before you spent the money.

Here’s why: nobody ever told you NAD+ is one thing. It isn’t. It’s a bucket with three completely separate problems:

• how fast it fills,

• how fast it drains, and

• what condition it’s in once it’s there.

And every product on the market is selling you a fix for exactly one of those three while marketing it like it solves all of them.

I’ve been running this stack myself (precursors, an NNMT inhibitor, sirtuin support, the works), and the biggest lesson wasn’t which compound works best. It was that “NAD+ boosting,” as an industry, has been misleading people by omission. Not with fake compounds. With an incomplete model of the problem.

So let’s fix the model first. Then let’s build the actual protocol.

Here’s what we’re going to unpack in this letter:

• Why NAD+ optimization isn’t one lever, it’s three, and which one you’re actually pulling

• Why “cytosol vs. mitochondria” might be the single most important concept nobody in this space talks about, and why it explains why the same protocol works for your friend and does nothing for you

• What’s actually consuming your NAD+ behind the scenes (spoiler: it’s not just age)

• Why sirtuins, not NAD+ itself, might be the thing you actually care about, and what really activates them (not resveratrol)

• The real relationship between NAD+ and your sleep as you age, including a personal experiment that went directly against the standard dosing advice

• IV vs. injections vs. oral: an honest cost-and-evidence breakdown of all three delivery methods, including the mechanistic problem nobody selling injections wants to talk about

• The specific misconceptions currently circulating in the NAD+ world, and why they’re wrong

I’ll also spend some time on a broader question:

• If total NAD+ isn’t the right thing to chase, what is, and how do you figure out, without an expensive lab test, which part of this system is actually your bottleneck?

Because ultimately, this isn’t a story about one supplement. It’s a story about matching the fix to the actual constraint, instead of matching it to whatever’s trending on your feed.

In the rest of this letter, we’re going to unpack all of the topics and questions raised above. Think of it as a one-stop shop for understanding NAD+, not as a supplement category, but as a system you can actually diagnose and fix.

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No water retention. No gyno. No ED.

Hand someone those two numbers without context and they’d assume I’m one blood draw from a hospital visit.

I’m not… and by the end of this you’ll understand exactly why, and why almost everything you’ve been told about “high estrogen” is measuring the wrong thing entirely.

Most guys on TRT are terrified of a number on a lab report. They see E2 at 40 and reach for a pharma AI they don’t actually need, chasing a figure that was never the real problem. I get the fear, I’m naturally prone to high-estrogen symptoms myself, bloating and puffy nipples included. But once you understand what actually predicts symptoms (not total estrogen, but the ratio, the pools, the clearance, the methylation) you’ll never look at a lab report the same way again. And you’ll probably never touch a pharma AI either.

And if your TRT guru's answer to a bad E2 number is "just inject more frequently," he's not wrong, he's just missing the bigger picture. Smaller, more frequent doses smooth out your peaks and can help a little, I'm not disputing that. But I've run that experiment on myself too (split doses, different esters, the whole playbook) and none of it moved my T:E2 ratio. Not even slightly. What actually shifted my numbers is everything in this article: ratio, pools, clearance, methylation, gut reabsorption. Injection frequency was never the real lever.

This isn’t another “top 10 natural AIs” roundup. It’s the most comprehensive estrogen course/guide/blueprint I’ve put together on estrogen management, built on my own repeat bloodwork, OAT, stool testing, HuMap, and full genome, not secondhand studies stitched together.

I’m the only lunatic out there that has tested nearly every known natural aromatase inhibitor, one at a time, with labs before and after. And I didn’t even have high estrogen! I ran every one of these tests anyway, purely to find out what’s real and what’s marketing so that at least someone on the web can tell people what really works instead of citing cell culture and animal studies as “proof”.

Here’s what’s we’re discussing in this article:

• What matters more than total estradiol.

• The most powerful natural aromatase inhibitors that slaughtered Aromasin in comparison

• The liver clearance and methylation pathways that decide whether your E2 is a real problem or just a number → 2-OH, 4-OH, 16-OH, COMT, bile flow, all of it, explained in plain terms

• A full lab-interpretation cheat sheet (ALT/AST, GGT, ALP, SHBG, LC-MS/MS E2/E1, estrogen metabolite ratios) so you can read your own bloodwork instead of guessing

• The single fix that took my T:E2 ratio from 13:1 while on an aromatase inhibitor to 30:1 with zero AI and what it proved about where my “high estrogen” was actually coming from

One honest caveat before we start: this is a supplement piece. The most powerful supplements that worked for me despite my diet and lifestyle dialled and me not being overweight. If you haven’t fixed your fat loss, insulin sensitivity, sleep, gut, and oils, go read the implementation guide first.

New here? Start here (the basics absolutely everyone should be implementing).

Let’s get into it.

Why you don’t want “high estrogen”

High estrogen is bad:

• Water retention → more estrogen means more angiotensinogen from the liver, which means more aldosterone, which means you’re holding water like a sponge.

• Puffy nipples → your ERα receptors sit right in glandular breast tissue, just waiting to get switched on.

• Gyno → leave those receptors activated long enough and “puffy” turns into permanent glandular growth no diet will remove.

• ED → causes vascular leakage and turns penile stem cells into adipose tissue instead of smooth muscle cells.

• Low libido → it doesn’t just wreck the erection, it kills the desire to want one in the first place.

• High prolactin → estrogen grows more prolactin-producing cells in your pituitary and mutes the dopamine that’s supposed to keep it in check.

• Irritability and aggression → testosterone is often blamed for aggression, but activating the estrogen pathway in the brain has been proven to cause aggression. Taking testosterone often make people calmer because it goes to DHT and 3a- & 3b-diol metabolites which are calming.

• Anxiety and mood swings → high E2 is the classic scapegoat for out-of-nowhere anxiety spikes and emotional whiplash.

• Higher glutamate signalling (greater excitation) → estrogen cranks up NMDA receptor activity in the brain, leaving you wired and overstimulated.

• “Estrogenic” fat gain → soft fat deposition around the hips, chest, and thighs gets pinned on high E2 every time.

• Increased blood clot risk → estrogen ramps up clotting factors, the same reason birth control pills carry a DVT warning.

• Elevated blood pressure → between the fluid retention and RAAS activation, hypertension is an easy one to hang on estrogen.

• Thyroid suppression → estrogen raises thyroid-binding globulin, locking up your thyroid hormone and leaving you “functionally hypothyroid” with normal-looking total T4 and T3.

• Sleep disruption → high estrogen routinely gets blamed for restless nights and poor sleep quality.

• Enhanced risk of cancer → estrogen is a known proliferation driver in hormone-sensitive tissue, from breast to prostate.

Now that we know that excess estrogen isn’t desirable. How high is too high. Should we cap it, inhibit it at all costs, or are these other things that are more important?

Absolute numbers vs ratios (and everything else that matters)

Almost all studies finding side effects from “high” estrogen aren’t actually looking at high estrogen. Take the male infertility literature: a follow-up to the classic Pavlovich/Schlegel endocrinopathy paper broke the numbers down directly. The “bad ratio” group was running testosterone around 274ng/dl and estradiol around 41pg/ml (T:E2 ≈ 7.2), while the “normal ratio” group sat at testosterone 423ng/dl and estradiol 30pg/ml (T:E2 ≈ 14.1) (R). Once an aromatase inhibitor corrected the ratio up to 37-40, semen parameters improved in both groups, including the group that started with the “better” numbers.

Look at that again: 41 vs 30pg/ml E2. Neither one is flagged as high on a standard lab report. But relative to a testosterone sitting under 500ng/dl, that 41 is high…in relation to testosterone. At a testosterone of 800+, that same 41 would be laughable.

Contrast that with what actually pathological estrogen excess looks like, since I brought up the genetic mutation angle earlier. Aromatase excess syndrome is a real condition → CYP19A1 massively overexpressed, autosomal dominant. In these patients the E2:T ratio runs over 10 in 75% of cases, against a normal male ratio of roughly 0.05–0.1. That’s a 100–1000x deviation from normal (R). That’s the range where a pharma AI is actually indicated. A guy running a gram of test a week worried that his E2 is 40 instead of 25 isn’t in the same universe as this.

So instead of staring at total estrogen, look at your testosterone-to-estradiol ratio. And even better, look at your total androgen pool vs your total estrogen pool. E2 can look low on paper while E1-S (estrone sulfate) is sky-high. If sulfatase is elevated, it “activates” that E1-S pool back into free E1, which then supplies local tissue with E2 conversion on demand, none of which shows up on a standard blood panel. The same logic runs on the androgen side: androsterone is about 7x weaker at the androgen receptor than testosterone, but it’s a potent aromatase inhibitor. If your androsterone is low, your aromatase runs higher regardless of what your T:E2 looks like on paper.

Then there’s liver clearance. This is where markers like 2-hydroxy-E1 and 2-hydroxy-E2 come in. These are the Phase I hydroxylation products your liver makes on the way to clearing estrogen out of circulation for good.

Then methylation. Methylation (COMT) converts 2OH estrogens into 2 methoxy estrogens. 2-methoxyestradiol is actually one of the more well-studied endogenous anticancer compounds on record, real antiangiogenic and antiproliferative activity, enough that it’s been developed as an actual cancer drug candidate (R, R).

What you want is efficient methylation: your COMT enzyme converting the reactive 2-OH catechol estrogens into the stable, inert 2-methoxy form before they get a chance to oxidize into reactive semiquinones. So a low 2OH-to-2-methoxy ratio (meaning your body is clearing catechol estrogens efficiently) is protective. Someone can have an E2 of 25 and still get estrogenic symptoms if their methylation capacity is poor and catechol estrogens are piling up instead of being neutralized.

The 2OH-to-16OH-E1 ratio is a separate, more established axis. 16α-OH-estrone is a strong, persistent estrogen receptor agonist, while 2-OH-estrone is a much weaker one that competitively blunts 16-OH signaling at the receptor. So someone can again have an E2 of 25 and still run hot estrogenically if 16-OH dominates their metabolism. One honest caveat worth including: the mechanism is solid, but the clinical evidence isn’t as supportive (R). Still worth keeping an eye on.

So what actually matters, roughly in order of how little of it shows up on a standard panel:

• T:E2 ratio (not absolute E2)

• Total androgen pool vs total estrogen pool (including the E1-S reservoir sulfatase can unlock) - HuMap test is great for this. DUTCH is also pretty good, but I prefer HuMap.

• Liver clearance capacity (2-OH-E1/E2 production)

• Methylation capacity (COMT converting 2-OH into 2-methoxy)

• Gut reabsorption (beta-glucuronidase reactivating conjugated estrogens back into circulation)

Everything above this is the why. Everything below is the how.

Premium subscribers get the exact protocols from here: the full methylation stack (including the PQQ dose that fixed my own 4-OH:4-methoxy ratio), the bile-flow fix that actually gets estrogen out of your body instead of recirculating it, the complete lab-interpretation cheat sheet so you can run this on your own bloodwork, and the full gut-reabsorption fix that took my T:E2 from 13:1 on an aromatase inhibitor to 30:1 with none — dosages, stacking order, what to run first, all of it.

Annual subscribers also get Ask Hans, trained specifically on my data and protocols, so you get answers to your own questions immediately instead of waiting on a reply.

Want me to look at your case personally instead? Contact me here.

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So they avoid anything that touches 5-alpha-reductase. Finasteride, dutasteride, saw palmetto. Anything that even sounds like it lowers DHT gets filed under “protects the hairline,” and anything that raises it gets treated like a threat.

That’s the wrong frame. And it’s costing people more than they realize.

5AR isn’t just “the hair loss enzyme.” It’s the enzyme that converts progesterone into allopregnanolone, one of the most powerful calming, GABA-boosting compounds your brain makes. It’s what deactivates cortisol into its cleared metabolites. It’s what makes THDOC, another neurosteroid tied to stress resilience. It’s what makes androsterone and 3α-diol, both of which carry their own downstream neurosteroid and androgenic roles.

Block 5AR, and you’re not just changing your hairline. You’re touching your entire neurosteroid pool → mood, stress buffering, sleep, GABAergic tone, all of it. This is well documented in post-finasteride syndrome patients, who show measurably collapsed neurosteroids in their spinal fluid, not just lower DHT.

So when something gets marketed as a “natural DHT booster,” most guys either avoid it out of fear, or take it and hope for the best without understanding what it’s actually doing.

Here’s what almost nobody talks about: even if PEA did increase 5AR in humans, it’s more likely to improve hair growth and quality due to better blood flow, lower stress hormones, better stress resiliency, lower inflammation, etc.

But here’s the real reason I ran this experiment, and it has nothing to do with hair.

I’m tired of watching supplement “gurus” post a single in vitro study and act like the science is settled. There is exactly one study showing PEA can increase 5AR activity and allopregnanolone… in glial cells, in a dish, via PPARα. That’s it.

Nobody knows if this holds up in an actual living human. Nobody knows if it touches the androgen pathway in vivo at all. And yet people are out there recommending PEA as a proven DHT booster, without ever running a single test.

That’s not confidence. That’s close to fraud.

So instead of repeating a claim I couldn’t back up, I tested it on myself.

I ran the same protocol I always run: a 4-point urine hormone panel. No guessing, no “I feel different.” Actual metabolite data, before and after.

This is my 4th HuMap test. HuMap is a urinary hormone panel → four collection points across the day, so you get both the daily rhythm and the total 24-hour output, not just a single snapshot. I've already run this same test on three other protocols before PEA, which means this isn't one isolated data point. I'm comparing PEA against my own prior results, so we can actually track a trend, not just react to a number that could be noise.

I wasn’t expecting what happened next. Not just on the hormone panel. On how I felt.

Calmer. Less reactive. The kind of easy-going state that’s hard to fake. My NexRing resting score that week hit 2 hours and 30 minutes. The highest it’s ever recorded. For context: on a normal day, without PEA, I’m lucky to break 15 minutes of resting score.

But before we get into my numbers, you need to understand what PEA actually is, because most of what’s said about it online barely scratches the surface. It’s not just a pain compound. It’s not just an anti-inflammatory. It’s a molecule your own cells are already making, on demand, every time you’re under stress and it touches almost every system relevant to how you feel, recover, and age.

Some of what PEA does, independent of anything to do with androgens:

• Calms an overactive immune response by stabilizing mast cells before they flood you with histamine and inflammatory cytokines

• Shifts brain immune cells (microglia) out of an inflammatory, neurotoxic state and into a repair-and-cleanup state

• Activates PPAR-α, a genetic switch that turns down NF-κB, TNF-α, IL-1β, and IL-6 (the core drivers of chronic low-grade inflammation)

• Strengthens the gut lining, reducing how much endotoxin (LPS) leaks into circulation and drives systemic inflammation

• Preserves your body’s own natural calming chemical, anandamide, by slowing the enzyme that breaks it down

• Increases neurosteroid production in the brain, including allopregnanolone

• Improves how your gut handles serotonin, keeping it in the calming pathway instead of shunting it into an inflammatory, anxiety-linked one

Does all of this without being a stimulant or a sedative. It’s a buffer, not a drug

That’s the backdrop almost nobody talks about. Now here’s what actually happened when I ran the numbers. Not a theory, not a dish full of glial cells, an actual human hormone panel.

The rest of this article is for premium members. I’ll walk through:

• What actually happened to my 5AR:DHT pathway and whether the direction matched the one in vitro study everyone's been citing

• What happened to my cortisol and neurosteroid markers that I wasn't even testing for

• Whether PEA's effect looks like real enzyme activity, or just substrate noise — the difference matters more than people realize

• My exact protocol, dosing, and stack, and who should be cautious with it

• The broader question this raises: how much should anyone trust a single in vitro study before it's been tested on an actual human

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You’ve done keto. Maybe carnivore after that. Bone broth was in your fridge at some point. You’ve had MCT oil in your coffee. You’ve read Ray Peat forum posts at 1am. You looked into TRT. You’ve got peptides in the freezer right now, or you’re thinking about it.

Some of it helped… for a while. Some of it did nothing. A couple of things made you feel worse and you quietly stopped mentioning them. And somewhere in the middle of all that effort, you’re still tired, still not recovering the way you used to, still waiting for labs to actually move, still not back to how you felt five or ten years ago.

Here’s the thing nobody tells you: that’s not a discipline problem. That’s not even a “you haven’t found the right protocol yet” problem. It’s what happens to almost everyone who tries to fix a system by cycling through tools instead of finding out what’s actually broken.

Before I show you the way out, look at the pattern first. Because once you see it, you can’t unsee it.

The Trend Graveyard

Health and fitness culture has run through an entire diet, supplement, or protocol roughly every 1–3 years for the last two and a half decades. Here’s the actual timeline:

• 2000 — South Beach Diet

• 2003 — Raw food diet

• 2006 — Master Cleanse (lemon, cayenne, maple syrup)

• 2007 — HCG diet

• 2010 — Paleo

• 2013 — 5:2 intermittent fasting

• 2015–16 — Bone broth (”the new coffee”)

• 2016 — Ketogenic diet goes mainstream

• 2017–18 — MCT oil / Bulletproof coffee

• 2018 — Carnivore diet

• 2019 — Keto search interest starts collapsing — down roughly 80% from its peak

• 2020 — Sirtfood diet, intermittent fasting 2.0

• ~2020–22 — Ray Peat / “bioenergetics” forums go from fringe to mainstream health-Twitter

• ~2021 — Circadian rhythm, morning sunlight, cold exposure (Huberman-era biohacking)

• 2022–23 — NAD+, rapamycin, longevity stacking (Bryan Johnson era)

• 2023–24 — TRT goes mainstream in men’s health spaces

• 2024–25 — Peptides (BPC-157, TB-500, GLP-1s) go fully mainstream

• 2025–26 — Bioregulators — the “next” peptide wave

Notice two things.

First: almost nothing on that list is wrong. Most of these have a real mechanism and a real reason someone felt better on them. That’s not the problem.

Second, and this is the part that matters: the cycle time is shrinking. Diets used to dominate for 5–7 years before the next one replaced it. Now a trend gets maybe 12–18 months before something newer takes its spot. If any one of these were actually “the answer,” the industry wouldn’t need a new one every year and a half. An entire multi-billion dollar content and supplement economy runs on the fact that the last thing didn’t fully work.

With these cycles, you’ve been playing a game that’s structurally designed to never end.

The Lifetime Test

Here’s a question almost nobody asks before starting a new protocol:

Are you willing to do this for the next 30–50 years?

Not eight weeks. Not “for now.” Not “until I feel better and then I’ll stop.”

But, thirty to fifty years.

Because that’s roughly how much runway you actually have left, and your body doesn’t care that a supplement stack was only ever meant to be a phase.

If the honest answer is no, one of two things is true: either you’ve found a genuine short-term tool for a specific, temporary problem (great, that’s what tools are for), or you’re using it as a patch for something you haven’t actually fixed yet, and the moment you stop, you’ll be right back where you started. Worse, usually, because now there’s a new deficiency or dependency layered on top.

You don’t have to take my word for how often this plays out. Look at what happens even to the interventions that do work, in people who were genuinely told to stay on them:

• Diets. A landmark analysis of long-term weight-loss studies found that one-third to two-thirds of dieters regain more weight than they lost within four to five years. Among people followed for two-plus years after a diet, 83% ended up heavier than when they started. (R)

• GLP-1 medications. In a nationwide study of semaglutide users, 18% had stopped within 3 months, 31% by 6 months, and over half (more than 50%) had discontinued within a single year. (R)

• TRT. In long-term tracking of testosterone therapy patients, only about half of topical users and roughly a third of short-acting injection users were still on treatment after just 3 months. Even among people who restarted after stopping, 40–50% dropped off again each cycle. (R)

• Supplements and daily medication generally. Real-world adherence tracking shows roughly 60% still following the protocol at 6 months, 41% at 1 year, and around 30% at 2 years. And that’s for things with a doctor and a clear medical reason behind them. Optional supplements fare worse. (R)

When something is a patch rather than a fix, your body (and your motivation) eventually stops cooperating with it, because deep down, patches require permanent maintenance, and almost nobody actually sustains permanent maintenance for something that isn’t fixing the underlying cause.

The tools that actually work long-term don’t feel like a 50-year sentence. They feel like removing a rock from your shoe. You don’t “adhere” to walking normally again.

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Why This Actually Happens

Go back to the trend graveyard for a second. Notice what almost every single one of those has in common:

They all operate at the level of the symptom or the tool, not the level of the system.

Keto changes what fuel you burn. Bone broth adds collagen and glycine. MCT oil changes fat metabolism. TRT raises one hormone. Peptides target one pathway. Every single one of these can genuinely help, if the thing it’s targeting happens to be your actual bottleneck. And every single one of them will do almost nothing or backfire if it isn’t.

That’s the trap almost everyone falls into: trying a tool before finding out whether it’s aimed at the right target. You end up with a garage full of things that worked for someone else, on a body whose actual constraint was never diagnosed in the first place.

Your symptoms aren’t random, and they’re not asking for a new trend every year. They’re signals from a system (digestion, nutrient status, stress buffer, thyroid, ferritin, gut, whatever it is for you specifically) and until you know which system is actually failing, you’re just rotating patches on top of a problem that’s still sitting there underneath all of them.

Why Listen To Me

Short version: I didn’t figure this out from a textbook. I lived through the collapse first.

I used to be the guy who needed three drinks to hold a conversation. Sober me was a shell - anxious, twitchy, couldn’t make eye contact with strangers. I told myself that was just my personality. It wasn’t. It was neurochemistry wearing a mask.

Then it got worse. My wife and I moved cities to build something from nothing. No money, no buffer, living in a cold, moldy flat, eating whatever was cheapest or skipping meals entirely. A stranger cut me off in traffic once and I had a full panic response (racing heart, blurred vision, shaking) over a car. My body had nothing left to buffer even a minor stressor with.

Over that stretch I dropped from 95kg to 80kg without trying to. My vision became ultra blurry past 5 meters. Hair shed more than a shaggy dog in summer. Constant dandruff, bacne, dull skin. Every training block ended in an injury instead of a PR. ED and premature ejaculation… in my twenties. Restless, shallow sleep that never felt restorative. Wide awake at 3am for no reason. And underneath all of it, a running commentary that something was fundamentally wrong with me as a person.

None of it was psychological.

• The hair loss was chronic stress and nutritional deficiencies.

• The injuries were low androgens and anabolic hormones.

• The ED and PE were endotoxin-driven sympathetic dominance and low neurosteroids causing vasoconstriction.

• The 3am wake-ups were cortisol from hypothyroidism and blood sugar dysregulation.

Every one of them resolved once I rebuilt what I now call the buffer, the reserve of nutrients, minerals, and gut integrity that decides whether ordinary stress bounces off you or takes you down.

I didn’t take that on faith. I tested a lot of superfoods to see how I’d respond to them (blood work, not just how I felt):

• 5 litres of milk a day for 30 days: cortisol dropped from 479 to 317 nmol/L in 2 weeks, fasting glucose went from ~100 to 85 mg/dL, and a major autoimmune-trigger bacteria (Klebsiella pneumoniae) was eradicated from my gut without touching an antibiotic.

• 15 oysters a day for 30 days: ferritin dropped from 432 to 282 and transferrin saturation from 51% to 31%, while I was eating roughly four times my normal iron intake. The zinc was outcompeting the iron for absorption.

• 420g of white button mushrooms a day for 2 weeks: my testosterone-to-estrogen ratio went from 23:1 to 32:1 and hsCRP dropped from 3.9 to 0.6. That’s a result 50mg/week of a prescription aromatase inhibitor never got me.

(And these are just a sneak peak at some of the experiments I did.)

Then I ran the same framework with the men I work with, and the pattern held. An MMA fighter at 300 ng/dL testosterone despite doing everything “right” (30,000 steps a day, multiple sessions a week, strict carnivore) hit 1,000 ng/dL by training less and eating more.

Another man stuck at 300 ng/dL for years, unresponsive to everything he’d tried, hit 700 once we fixed his gut.

A guy with 10-a-day diarrhea for a decade, who’d seen every specialist available to him, resolved it in days by adding a bile acid called UDCA.

All of this is published on my Substack with the actual lab numbers, as I ran each experiment.

The Way Out: Find the System, Not the Next Trend

This is the sequence that actually ends the cycle. The one this whole series is built on. Not a new trend to add to the graveyard. The order you work through to find out what’s actually broken, so you stop needing a new protocol every 3 months.

Stage What it fixes Full breakdown

1. See the pattern: Groups your symptoms into the system that’s actually failing, instead of chasing each one individually → The Symptom Master Checklist

2. Fix digestion: Nothing else works (not the diet, not the supplement, not the peptide) until breakdown, absorption, and transit are working → The Ultimate Guide on Fixing Digestion

3. Simplify your inputs: Gives you clean feedback instead of guessing which of 15 ingredients is the problem The 1 Protein + 1 Carb Masterclass

4. Get calories right: Lets you manage weight without wrecking thyroid and stress tolerance in the process → How to lose fat without counting calories or tanking your testosterone

5. Actually replace what’s depleted: Fixes the deficiencies “eating healthy” quietly never touched → Why You’re Deficient Despite Eating Well

6. Rebuild your stress buffer: Restores the capacity that makes ordinary stress stop feeling catastrophic → Why You Wake Up Anxious & Exhausted

7. Find your actual bottleneck: Thyroid, ferritin, mold, metals, methylation, histamine. The 14 things that quietly cap everyone’s progress, in the order to check them → The 14 Hidden Reasons You’re Not Getting Results

8. Then, and only then, accelerate: Peptides, nootropics, and everything else on the trend graveyard, used on purpose, on a system that’s actually ready for them → The stack that changes everything

This is the difference between a tool and a fix: a fix, applied to the right system, makes the tools you add later actually work. Often at a fraction of the dose, cost, and time everyone else is throwing at the problem blind.

If You Have One Specific Problem Right Now

If you don’t need the whole sequence yet (you just want the fire in front of you put out) start here instead:

Gut & digestion → Fix Slow Transit Time & Constipation → Heal Leaky Gut & Lower Endotoxin → Improve Lactose Tolerance & Digest Dairy Again → Increase Butyrate & Improve Your Gut Microbiome

Hormones & mental function → Fix Hypothyroidism → Maximize DHT → Lower Estrogen Naturally: Block Aromatase / Promote Estrogen Excretion → Fix Anxiety Through Hormones & Neurosteroids → Rebuild a Nervous System That Doesn’t Overreact

Sexual function → Fixing Premature Ejaculation → Fixing Erectile Dysfunction: Part 1 / Part 2 / Part 3

Two Ways Through This

Path A — Work it yourself. Go through the 8 links above, in order. Test each stage on yourself. This works. It’s exactly what I did. It also took years, because I was the test subject and the lab at the same time, with no one telling me which stage I was actually stuck on.

Path B — Skip the guessing entirely. Send me your symptoms, diet, current stack, and labs (if you have them), and I’ll tell you exactly which stage you’re in and which of the 14 bottlenecks is most likely capping you, so you stop adding to your own trend graveyard.

→ Get your personalized health report here

And if you’d rather have a direct line whenever something comes up (a new symptom, a lab result you don’t understand, a protocol you’re wondering whether to trust) annual members get access Ask Hans, direct access to me (all my knowledge installed into one database for instant answers)

Start Here

You don’t need to try one more thing this year. You need to know which system is actually failing.

Go back through the sequence above. Find your stage. Read that one article first.

That’s how the cycle actually ends.

Why your symptoms aren’t random. And the exact sequence to fix what’s actually wrong (not just what’s loudest)

Imagine you never got a single symptom, and then one day your leg just fell off.

Weird example. But it makes the point: symptoms aren’t the problem. They’re the only reason you find out there is a problem before it gets serious.

Most people treat symptoms like an annoyance to patch.

• Headache → aspirin.

• Low energy → caffeine.

• Poor sleep → melatonin or benzos.

• Hair loss → finasteride.

That’s the slow way to get nowhere, because you’re never touching what’s actually driving it.

A slightly better way is to chase the root cause of each symptom individually → magnesium for anxiety, T3 for cold hands, morning sunlight for sleep. This works... a little. Everything improves marginally. Nothing sticks. You add more supplements, try more diets, and six months later you’re in the same place with a bigger cabinet.

Here’s what actually works: stop treating symptoms as isolated events and start treating them as signals from a system. Nobody “just has bloating.” They have bloating + brain fog + poor sleep + low libido. And all four are pointing at the same failing system. Once you can see which system is failing, the individual symptoms stop being confusing. They become obvious.

That’s the idea behind this roadmap. Below is the exact sequence (the one I use with clients, and the one this entire 8-part series is built on) for going from “randomly patching symptoms” to “systematically fixing the thing that’s actually broken.”

More energy. Faster recovery. Looking and feeling better. Labs that actually move. Stronger androgen signaling. Making progress in the gym again. Being around, and being sharp, for longer. It’s all downstream of the same map.

The Map

Everyone who successfully fixes their energy, labs, recovery, and hormones moves through the same stages, in the same order. Skip a stage, or work them out of order, and every stage after it gets harder and slower.

Stages

• Patch Mode: Treating each symptom as its own problem. Most people never leave this stage.

• Pattern Recognition: Grouping symptoms into clusters and seeing which system is actually failing.

• Digestive Reset: Fixing breakdown, absorption, and transit. Nothing downstream works until this does.

• Input Simplification: Reducing meals to 1 protein + 1 carb so your body can finally give you a clean signal.

• Caloric Control: Managing weight without wrecking energy, thyroid, or hormones in the process.

• Nutrient Loading: Rebuilding what years of “eating healthy” quietly failed to replace.

• Buffer Rebuild: Restoring your capacity to absorb stress without it wrecking digestion, sleep, and hormones.

• Bottleneck Identification: Finding the one or two things (thyroid, ferritin, metals, mold, methylation…) actually capping your progress.

• Acceleration: Layering in tools that only work once the first seven stages are handled.

Find yourself below. Most people reading this are somewhere between Patch Mode and Acceleration and most people don’t know where exactly they are or the order they’re following.

Stage 0: Patch Mode

You’re here if: you have a supplement or medication for every symptom, and a new one keeps getting added every few months. Headache → pill. Tired → coffee. Can’t sleep → melatonin. Nothing is actually resolving… it’s just being muted.

The trap: it works just often enough to feel productive. You feel like you’re “doing something,” so you never step back and ask why you needed the patch in the first place.

What moves you forward: stop treating the symptom as the target. Write down every symptom you currently have, without trying to explain any of them yet.

Stage 1: Pattern Recognition

You’re here if: you’ve noticed your symptoms cluster (bloating always shows up with brain fog and bad sleep, or fatigue always comes with cold hands and low libido) but you haven’t connected the dots yet.

The trap: trying to find a separate root cause for every single symptom sends you on a wild goose chase. Different diets, more supplements, more protocols. Marginal improvement on all of them, resolution on none.

What moves you forward: group your symptoms into the 9 clusters (digestion, energy/brain, sleep, nervous system, skin/hair, metabolism/thyroid, inflammation/immune, sexual health, circulation) and notice which cluster is loudest. That’s your starting system.

→ Full breakdown: The Symptom Master Checklist

Stage 2: Digestive Reset

You’re here if: you’re already eating “clean” and still bloated, foggy, or crashing after meals. You’ve tried removing foods, adding probiotics, more enzymes. Some of it helps a little, none of it fully resolves it.

The trap: digestion doesn’t fail in one place, it fails in a sequence (stomach acid, enzymes, bile, endotoxin, transit). Fixing “gut health” in general, without knowing which step is actually broken, is why most gut protocols only partially work.

What moves you forward: go through the sequence in order. Stomach acid and enzymes first (most people are stuck here and don’t know it), then bile flow, then transit time. Leaky gut is almost always the result of this sequence breaking down, not the starting problem.

→ Full breakdown: The Ultimate Guide on Fixing Digestion

Stage 3: Input Simplification

You’re here if: you’ve fixed some digestion basics but still can’t tell which foods are the problem, because every meal has five ingredients in it.

The trap: complex meals feel healthier (”more variety!”), but they make it impossible to get clean feedback from your own body. You can’t fix what you can’t isolate.

What moves you forward: one protein, one carb, per meal. Not because it’s a magic diet, because it turns every meal into a controlled experiment. This alone resolves a surprising amount of “unexplained” bloating and energy crashes.

→ Full breakdown: The 1 Protein + 1 Carb Masterclass

Stage 4: Caloric Control

You’re here if: digestion and inputs are cleaner, but body composition still isn’t moving or it’s moving in the wrong direction.

The trap: going too aggressive on the deficit tanks thyroid output and stress tolerance, which stalls fat loss anyway. Or you’re “eating at maintenance” on paper but portion creep, cooking oil, and alcohol have quietly erased the deficit.

What moves you forward: structure, not restriction. Use the simplified meals from Stage 3 to build a deficit you don’t have to think about. Calories are the lever, nutrient quality determines how good the outcome feels, not whether it happens.

→ Full breakdown: How to lose fat without counting calories or destroying your testosterone

Stage 5: Nutrient Loading

You’re here if: you eat well by every conventional measure and you’re still tired, still not recovering, labs still borderline. You’ve done “clean eating.” It wasn’t enough.

The trap: eating whole foods isn’t the same as absorbing them. Soil depletion, anti-nutrients, poor food combining, and genetics all mean the RDA was never actually your number.

What moves you forward: build meals around the five most nutrient-dense foods that exist (liver, oysters, egg yolks, dairy, red meat) instead of trying to hit targets with twenty plant foods that block each other’s absorption.

→ Full breakdown: Why You’re Deficient Despite Eating Well

Stage 6: Buffer Rebuild

You’re here if: you feel “wired but tired,” small stressors feel disproportionately large, and things that used to be manageable now feel like too much.

The trap: treating the output (anxiety, poor sleep, irritability) with a supplement instead of rebuilding the underlying capacity to absorb stress in the first place.

What moves you forward: stress isn’t the problem. A depleted buffer is. Restore metabolic safety (enough carbs, enough salt), fix digestion, then restore the specific minerals and compounds that got burned through.

→ Full breakdown: Why You Wake Up Anxious & Exhausted

Stage 7: Bottleneck Identification

You’re here if: you’ve genuinely done the work (diet, digestion, stress) and something is still capping your progress. This is the stage where most self-directed effort quietly stalls out.

The trap: guessing. Running a heavy metal detox when the real issue is thyroid. Chasing histamine when it’s actually ferritin. Every wrong guess costs months.

What moves you forward: work through the 14 bottlenecks in priority order → environmental exposure first, then gut, then thyroid, then ferritin, then everything else. One or two of these are almost always the actual ceiling.

→ Full breakdown: The 14 Hidden Reasons You’re Not Getting Results

Stage 8: Acceleration

You’re here if: the foundation is genuinely solid and you’re looking to compound your results faster → peptides, nootropics, mitochondrial support, thyroid acceleration.

The trap: using any of this too early. The same compound that produces a dramatic result in a functioning system produces almost nothing (or side effects) in a broken one.

What moves you forward: layer these in only once Stages 1–7 are handled. This is the reward for doing the work, not a shortcut past it.

→ Full breakdown: The stacks that changes everything

Where Most People Actually Get Stuck

Almost nobody fails because they’re lazy. They fail because they jump straight to Stage 5, 6, or 8 while still standing on Stage 0 or 1. You can’t out-supplement a digestion problem. You can’t out-protocol a bottleneck you haven’t identified yet.

The order matters more than the tactics.

Two Ways To Get Through This Map

Path A — Work it yourself. Read all 8 parts of this series (linked above, all free). Test each stage on yourself. Track what changes. Find your own bottleneck by process of elimination. This works — it’s exactly what I did. It also took years, because I was the test subject and the lab at the same time.

Path B — Skip the trial and error. Send me your symptoms, diet, current stack, and labs (if you have them), and I’ll tell you exactly which stage you’re actually in and which bottleneck is most likely capping you. No guessing, no six-month detour into the wrong protocol.

→ Get your personalized health report here

And if a question comes up mid-week and you don’t want to dig through 8 articles to find the answer → annual members get direct access via Ask Hans, so you get a real answer instead of a forum guess.

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But pregnenolone isn’t just the precursor to all other hormones, it also has unique effects/benefits of its own.

Also, the way you take pregnenolone (dose, route (oral, topical, sublingual, etc.) will determine how you feel on it.

In this article, I break down:

• The mechanisms of action and benefits of pregnenolone

• The pregnenolone steal

• Different routes and doses of taking it

• How to enhance the calming effects of pregnenolone

• How to enhance the nootropic effect of pregnenolone

I also compare it to other hormones like progesterone, DHEA and testosterone with the different routes of administration to help clarify how each route is most likely to “behave” and effect you.

Effects, Mechanisms of Action, and Benefits

What the human evidence actually supports

Strip away the anti-aging and “hormone balance” marketing, and the clinical evidence for pregnenolone clusters around a narrower, more specific set of findings:

• Adjunctive benefit for negative symptoms in schizophrenia: reduced blunted affect, avolition, and anhedonia

• Greater reduction in depression ratings versus placebo in trial data

• Meaningful pain relief in veterans with chronic low-back pain: roughly half of pregnenolone-treated participants hit a 20%+ reduction in pain intensity, versus about a quarter on placebo

• Reduced provoked craving, anxiety, and autonomic stress response in early alcohol-use-disorder research

• A 2025 preprint reporting lower craving and reduced cocaine use at 300mg/day

• Lower irritability scores sustained over 12 weeks

• Neuroprotective, anti-inflammatory, and myelination-supportive effects in animal models

These are the main human data on it. There are a host of other interesting animal research, however, we don’t know if it’s applicable to humans at all. We know that what often happens in animals due to a specific dose/compound, rarely translates to humans like that.

So for now, I’m not going to focus on what the animal research shows.

What pregnenolone actually does

For a long time it was thought that pregnenolone was only a precursor to other hormones. However, pregnenolone itself has beneficial effects.

When pregnenolone is made in large amounts, it gets turned into pregnenolone sulfate (PS), kind of like a storage form. And PS also has effects.

• Increases NMDA receptor signaling, which can support alertness, plasticity, dopamine tone, and memory encoding, but can also tip someone toward excitation and anxiety depending on baseline glutamate load.

• Inhibits the GABA-A receptor signaling, the opposite of what most people expect from a “calming hormone precursor.” Meanwhile allopregnanolone, further downstream, is one of the most potent positive GABA-A modulators known, which is exactly why it’s now an FDA-approved postpartum depression drug under the name Brexanolone.

• Acts as a negative allosteric modulator/inhibitor of glycine receptors. This can help with more alertness or arousal, greater sensory responsiveness and potentially improved NMDA-dependent plasticity. However, it can also contribute to anxiety, irritability, disrupted sleep, increased pain sensitivity, or susceptibility to overstimulation.

• Acts as a sigma-1 receptor agonist alongside DHEA-S. Sigma-1 receptors influence calcium handling, ER-mitochondria signaling, ion channel trafficking, pain processing, ATP production, neuroplasticity and mitochondrial quality control.

• TRPM3 activation: pregnenolone sulfate activates this calcium-permeable channel, with downstream effects on pain and neuroendocrine signaling.

• CB1 modulation: native pregnenolone appears to act as a pathway-specific negative modulator of certain CB1 signaling, which may blunt some THC effects without functioning as a conventional cannabinoid antagonist.

• CLIP-170 binding: native pregnenolone binds this microtubule plus-end protein and promotes microtubule polymerization and cell migration in experimental systems, a mechanism that hints at nerve repair and neurodegeneration applications that haven’t been clinically tested yet.

• TLR4 antagonism: pregnenolone (via conversion to allopregnanolone, and pregnenolone sulfate directly) interferes with TLR4 signalling (the endotoxin receptor), thus reducing inflammation.

The net effect of pregnenolone (especially the sulfated form) is excitatory, but also anti-inflammatory.

If your physiology routes pregnenolone toward pregnenolone sulfate, DHEA, and androgenic, excitatory signaling, you’re more likely to feel activated, clearer, restless, anxious, acne-prone, or wired at bedtime.

If it routes toward progesterone and allopregnanolone, you’re more likely to feel calm, sleepy, less anxious, or even emotionally blunted.

This is the actual mechanism behind why pregnenolone reports on X are so wildly inconsistent.

The only way to know for sure is to test for yourself.

“Pregnenolone steal” oversimplifies it

Some people are afraid to use pregnenolone because of the idea that under stress, more pregnenolone will be used to create cortisol. This leaves less precursor for the production of allopregnanolone, testosterone and other androgens.

So if you’re under stress, taking pregnenolone will lead to higher cortisol.

However, it’s an oversimplification.

Stress-driven steroid shifts are governed largely by the brain, ACTH signaling, adrenal enzyme expression, and substrate availability, not by pregnenolone literally running out and getting hijacked by one pathway.

You have pregnenolone is different parts of the body (testes, adrenals, brain, etc). Under stress, adrenal pregnenolone production is upregulated to create cortisol. Keep in mind that cortisol can be converted to THDOC, which is a positive modulator of the GABA receptor, thus enhancing GABA signalling.

Stress doesn’t “steal” brain or testicular pregnenolone for cortisol production. But stress (ACTH and cortisol) can reduce testicular steroidogenesis, thus leading to lower levels of testosterones. This isn’t due to pregnenolone steal, but rather inhibition.

Taking pregnenolone will increase pregnenolone levels in different tissues of the body where it will be spot specifically/locally used, including the brain. In the brain it can be used to create allopregnanolone, which enhances GABA-A signalling and can dampen stress-responsive CRH-neuron activity and reduce ACTH responses to specific stressors.

Now, In Terms of How to Use It

The rest of this article is for premium members.

We’ll cover:

• All four ways to take pregnenolone (oral, topical, sublingual, and intranasal)

• What actually differs between them

• Which one you probably want based on what you’re after

• Doses

• Pros and cons of each

• How to stack additional compounds to supercharge the specific effect you’re chasing.

Taking pregnenolone different ways produces genuinely different results, not just different intensities of the same result. How it’s stored, which metabolites it converts into, the ratio between those metabolites, and how long each one sticks around all shape how you actually feel on it. Change the route, and you change all four of those variables at once.

If you want my personal help digging into your specific case and building a protocol around it, here’s how to work with me.

Read more

He didn’t have PFS. He had a nervous system that was already leaning obsessive and sympathetic-dominant, and finasteride didn’t create that; it just removed the buffer that had been keeping it in check. Every “fix” he tried after that (thinking the problem was PFS) made things worse, because each one added excitatory load or gutted what inhibitory capacity he had left.

Before I ever looked at a single hormone value, the timeline itself told most of the story.

Before the drugs: a hyper-focus on preventing hair loss he didn’t have (claimed as prevention). Being hyperfocused/obsessed over something isn’t bad per se, but obsessing over something that isn’t an issue can be a sign. OCD isn’t a character flaw, it’s simply caused by certain hormone and neurotransmitter balance.

P.S. This article/info isn’t to slander anyone. It’s to demonstrate timeline and symptoms that helped me identify what was going on and how to fix it. I’m sharing this because others might be in a similar situation, where they need to be given an alternative explanation to start focusing on the true root cause and start fixing that.

Timeline:

• Baseline: TRT at 26, 160mg/week, high T and DHT, no symptoms

  • This isn’t really a TRT dose, but a low dose cycle for muscle building purposes…nothing wrong with that.

• Starts obsessively preventing hair loss that hadn’t happened, escalates to topical finasteride plus other actives (vitamin A, caffeine, minoxidil, etc.)

• While on topical finasteride, he started experiencing mild anxiety and minor sleep disturbances, still functioning normally, traveling for work, dating, exercising, and enjoying life while on it.

• He stopped finasteride because he had his first-ever panic attack.

• He recovers ~90% within about a week while still using TRT/hCG/Proviron.

• Starts researching PFS and becomes convinced anyway that it’s PFS, despite the fast, clean recovery.

• Seeks out a DHT-based “solution” marketed as the fix.

• DHT megadose (200mg daily) → rapid, severe decompensation → worse after the “treatment,” not before.

• Brain cyst discovered on workup → fixates on the cyst as the cause → specialists rule it out as incidental.

• Returns to PFS belief → adds DHEA and pregnenolone alongside DHT → continued deterioration → hospitalization → OCPD diagnosis.

This pattern isn’t PFS. PFS is when you get negative symptoms, which is why it’s called post finasteride syndrome. Rapid resolution of symptoms after stopping finasteride isn’t PFS.

Getting symptoms after using DHT is rather DHT-induced syndrome (I just made that up).

This article isn’t just about finasteride

It’s about sympathetic dominance causing symptoms like anxiety, hyperemotionality, insomnia, restlessness, rumination, fixation, panic, OCD, etc.

Finasteride is one way to get there. So is chronic stress, poor sleep, restrictive dieting, overtraining, alcohol (or other drug) withdrawal, or other medications that touch the same pathways. If you recognize the combination → anxious but flat, unable to let go of one explanation, “I know something’s wrong but nothing I try fixes it”, this applies to you whether or not a 5-alpha-reductase inhibitor was ever used.

Why this rules out classic PFS

Real PFS, the kind with persistent mental, sexual and muscular pathology, doesn’t typically resolve to 90% in about a week off the drug.

PFS often occurs when people stop the drug, which is why it’s called post finasteride syndrome. He got symptoms while on the drug and they resolved >90% in about a week after stopping. That’s not PFS.

He experienced no muscular or sexual side effects, only mental/cognitive. Yes, not everyone experiences the same side effects, but what led me to think that it was PFS was because he already had minor signs of these symptoms before he even used finasteride.

And his main issues didn’t come from finasteride, it came after he used very high doses of DHT. So this was DHT induced dysfunction.

In the rest of the article, I discuss exactly:

• what the mechanism is,

• why he was predisposed to this, and

• why finasteride simply revealed the underlying condition

• why DHT made everything worse

• what I recommended he do to fix the underlying problem (it’s not just upregulate 5AR)

If your sympathetic nervous system (fight and flight) is feeling out of control, this article is for you.

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The standard acne explanation is saturated fat, dairy, IGF-1, lipogenesis, and skin bacteria. All of those play a role sometimes. None of them hold up as the root cause.

Someone with very low IGF-1 can still have acne. Someone with very dry skin can still have acne. Someone with sky-high IGF-1 can have completely clear skin. My own skin runs oily and I don’t break out. If the standard model were actually the mechanism, these people wouldn’t exist.

This is the same pattern as hair loss. The standard fix there is finasteride, a drug with a long list of side effects for a meaningful chunk of people who take it. Acne has its own version of that same story: isotretinoin, a vitamin A analog, prescribed as the default heavy-duty fix. It works for a lot of people in the short term and it also causes serious gut issues in some, along with dry eyes that can persist for years, sometimes decades, after stopping. When the standard explanation for a condition is incomplete, the standard fix tends to be a blunt instrument, and blunt instruments have a cost.

This article is the alternative explanation. Acne is systemic inflammation showing up on your face, driven by your gut, not a simple oil, hygiene, or hormone problem. The same food can be harmless in a healthy gut and a breakout trigger in a compromised one. That’s the actual mechanism worth chasing.

TL;DR

• Acne isn’t caused by oil, hygiene, or any single food, it’s systemic inflammation from a compromised gut showing up on your face.

• Histamine, insulin resistance, and hormonal fluctuations act as amplifiers, not root causes.

• Standard fixes like isotretinoin and blanket food elimination treat the symptom while ignoring the terrain.

• Fix digestion, bile flow, transit, and the gut ecosystem first, most “hormonal” or “genetic” acne resolves on its own.

In this article I discuss exactly how to address the root cause.

The Gut-Skin Axis

Dysbiosis, a leaky barrier, and low secretory IgA let LPS (endotoxin) cross into circulation. That LPS activates keratinocytes and sebocytes before you’ve even reacted to a “trigger” food. Low IgA means less mucosal defense, so more of what’s in your gut ends up talking directly to your immune system, and your immune system talks back through your skin.

One more thing worth saying early: leaky gut is the result, not the cause. It’s what happens when digestion breaks down upstream (acid, enzymes, bile, transit) and inflammation stacks on top. Sealing the barrier without fixing what’s tearing it open is a patch, not a fix. Keep that in mind as you read the rest of this.

Histamine: The Inflammatory Gain Knob

Histamine isn’t the root problem. It’s the volume dial.

High DAO/HNMT clearance = small triggers stay small. Low clearance = minor foods turn into flare days.

The histaminic acne phenotype looks like: red, itchy borders, flushing, flares from alcohol, leftovers, and aged or fermented foods. And most chronic histamine reactivity traces back to overgrowth and intestinal inflammation degrading DAO, not the food itself.

If you start itching (skin, scalp) when you exercise or start to get warm, that’s partly driven by histamine.

Lowering histamine load has 5 angles:

• kill histamine-producing bacteria,

  • Starve them by following a low fiber diet, consisting mostly of animal foods

  • Avoid high FODMAP foods that trigger your symptoms like garlic and onion

• seal the gut so histamine isn’t absorbed,

  • By eating non-inflammatory foods

  • Using compounds like zinc carnosine, vitamin C and BPC-157

• lower intestinal inflammation so that DAO expression increases,

• stabilize mast cells so they release less in the first place, and

  • 600-1200mg PEA +1-2g quercetin (depending on the severity)

  • Ketotifen is a very good mast cell stabilizer, but can cause a lot of fatigue due to it also being a histamine blocker

• support methylation (HNMT uses SAMe).

  • B-vitamin rich diet

  • Supplementing TMG (trimethylglycine aka betaine anhydrous)

Food as Amplifier, Not Villain

Food generally isn’t a direct problem, but it can be a trigger depending on your state of health. If gluten causes leaky gut, more histamine will be absorbed. If you have histamine-producing bacterial overgrowth, eating high-fiber will feed them and make them grow. If your digestion is “weak”, then eating hard to digest complex meals can create intestinal inflammation due to incomplete digestion.

Milk is a common trigger for some people, but it’s due to a variety of reasons. It can be due to:

• excess fat releasing too much bile → switch to low fat

• lactose intolerance feeding histamine producing bacteria → switch to lactose free or cheese

• A1 casein sensitivity causing intestinal inflammation → switch to A2 or goat milk

Same food, different gut, different outcome. In an intact gut, foods cause small ripples. In a damaged one, the same foods generate endotoxin, histamine, and cytokine waves that show up as flares. Judge any food on three axes: inflammatory load, digestive workload, and histamine/mast-cell potential. Nothing is universally “acne-safe” or “acne-causing.” Context is everything.

Frequency matters as much as the food itself. Eating a trigger once might not cause problems. But eating the same trigger daily, or even a few times a week, compounds. Each exposure adds inflammation on top of inflammation that hasn’t fully cleared from the last one, and the gut and skin never get a clean window to reset. This is why symptoms can take 4+ weeks to fully clear even after the trigger is removed entirely.

You’re not just waiting out the last meal, you’re waiting out weeks of stacked inflammatory load finally draining down. If you test a food once and feel fine, that doesn’t mean it’s safe on repeat exposure, and if you cut something and don’t see improvement in a few days, that’s not proof it wasn’t the problem, it may just mean the backlog hasn’t cleared yet.

Still on the fence? We're #1 in male optimization on Substack and Top 10 in Health & Wellness globally, built on one rule: never insult your intelligence. Data-first, nuance-always, no fluff. Ever. The 1,000+ premium readers inside know exactly what that's worth.

In this article:

• Which specific food categories actually drive flares, and why fiber, FODMAPs, and lectins aren’t the villains everyone assumes

• Why high fat and high carb eaten together is a bigger oily-skin trigger than either alone

• The metabolic side: insulin resistance, hormonal fluctuations

• Antibiotics vs. natural compounds

• The stool-based diagnostic that tells you which direction your bile is broken, and why that matters specifically for oily skin

• Which probiotic strains actually calm inflammation, plus the topical actives worth using

• A full stress-to-cortisol protocol, in the right order, not just “reduce stress”

• The most nutrient-dense, easy-to-digest foods to prioritize before reaching for any supplement

• The mechanical and environmental triggers most people never think to check, pillow, laundry detergent, hair products, and more

• The exact tiered protocol and step-by-step sequence to start fixing this today

Let’s get into it!

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“Shouldn’t I just focus on fixing leaky gut first?”

A client asked me this recently. Makes sense on the surface. Leaky gut lets toxins into the body, drives inflammation. Seal it, done, right?

Not quite.

Zinc carnosine soothes gut inflammation and repairs the lining. But if you’ve got nutritional deficiencies, bacterial overgrowth pumping out toxins, sluggish transit, bad bacteria converting bile into inflammatory forms, and poor digestion feeding the wrong bugs, zinc carnosine is a patch on a leaking roof. Helps a bit. Fire still raging underneath.

This is why so many men cycle through supplements, feel better for two weeks, crash again. Wrong order. Here’s the right one.

What’s Actually Causing It (Quick Scan)

• Poor food combinations

• Processed foods → fat + sugar + gluten stacked in one bite

• Individual triggers → gluten, A1 casein, nightshades, chilli, histamine load

• Fat type and quality (even from whole natural foods)

• Carb type and quality (even from whole natural foods)

• Transit time, too slow or too fast

• Chronic stress

• Medications → nearly all of them touch the gut somehow

• Antibiotic history

• Poor hydration

• Nutritional deficiencies

• Undiagnosed dysfunction → thyroid, H. pylori, bile, overgrowth

Most of this list gets fixed with food and behavior. No supplement, no test. Here’s the sequence.

TIER 1: Food, Combinations, Behavior

80-90% of you fix this here. Not with a stool test. Not with a supplement stack. With what’s on the plate and how you’re combining it.

Simplify first

One protein, one carb, per meal. Digestion doesn’t fail randomly, it fails when total load exceeds capacity. 100g of red meat alone, fine. Add butter, rice, garlic, onions, sauce, salad, veggies, and more meat, now you’ve got symptoms. Fewer variables, less residue, less fermentation.

Full guide on the one protein one carb source meal plan

Fat type changes everything

Coconut oil (lauric, myristic acid) is medium-chain, mostly skips the bile-lipase system entirely. Less likely to cause issue unless overdone.

Tallow, lard, beef fat is long-chain, needs the full bile cycle running. If bile flow is sluggish, long-chain fat is the riskiest category on your plate. Dairy fat and olive oil sit in the middle, easier than tallow, harder than coconut. People often tolerate dairy fat better than tallow.

Full guide on different fat types and how to structure them correctly in the diet

Matrix matters more than macros

Food doesn’t just consist of protein, carbs and fats (in different ratios of course). There are different amino acid ratios, fatty acid profiles, carb types, vitamins, minerals, liquid vs solid, etc, all of which impact digestion and gut health differently.

Someone might tolerate lamb and pork better than beef because it’s lower in iron with a different fatty acid profile.

Meat rich in sulfur amino acids (taurine, cysteine) can that feed Bilophila wadsworthia, a bacteria that converts bile into hydrogen sulfide, a known colon irritant. Dairy fat doesn’t do the same. Both are saturated fat, but the body responds differently to each. This is why lamb and dairy often sit better than beef even at equal fat content.

Gizzards vs. oxtail

Oxtail is very high in fat, whereas gizzards are extremely low, which impacts digestion differently, despite both being excellent sources of collagen.

“Whole food” doesn’t mean uniform food. Test the cut, not just the species.

The combination multiplier

Protein and fat slow gastric emptying. Adding starch on top can cause more gut issues because transit is slower and the bile profile is different. Stack fat and starch together in a gut that’s already struggling and you get more gas, pressure, and endotoxin than either macro causes alone. Ribeye and potatoes can wreck someone, but if they swap to fruit or honey, digestion might be perfect. Or swapping the protein to sirloin will speed up gastric emptying and improve starch tolerance.

Carb type is not one category

Fruit is fast-oxidizing, fructose needs less insulin, and there’s a lot more liquid in fruit, which is cooling to the body. Starch (potato, rice, oats) is slow-oxidizing and warming. Ripe banana ≠ green banana, different sugar profile, different gas response. Waxy potato ≠ glassy potato. Test the variety, not just the food group.

Full carbohydrate guide here

FODMAPs are all different

Short-chain carbs (fructans, GOS, lactose, polyols) aren’t absorbed and they are food for bacteria. Most people don’t have a FODMAP in general sensitivity. They have an intolerance to a specific type. E.g. sensitivity to garlic and onion, but not apples. Bloat on cabbage, but fine on bananas.

Also, fructose malabsorption and lactose intolerance aren’t inherently bad, they act as prebiotics in a healthy gut (they help beneficial bacteria grow). Only a problem when overgrowth or inflammation is already present and they allow the growth of inflammatory bacteria.

Processed foods stack the worst combination possible

Baked goods and packaged snacks combine fat, sugar, and refined flour/gluten in a single bite, a combination the gut almost never sees in whole food form and has no evolved capacity to process cleanly. Not one ingredient. The stack.

This is why I like the 1 protein 1 carb source meal plan so much because you don’t have to think about anything or wonder if there will be inflammatory compounds in your meal.

Polyols are the sneaky one

Sorbitol, xylitol, erythritol in “sugar-free” products. Classic hidden bloating trigger nobody suspects because the product is marketed as the healthy option.

Individual triggers, test don’t assume

Gluten, nightshades/solanine, chilli, lactose (only if lactase is genuinely low), A1 casein. All highly individual. React to potato but not sweet potato → solanine, not starch. React to standard milk but not A2 → casein, not lactose.

Histamine is a symptom, not the root

Fermented foods, aged cheese, cured meat, leftovers, wine, liver and (counterintuitively) bone broth are all high-histamine. But most chronic histamine reactivity traces back to histamine- and endotoxin-producing bacterial overgrowth and intestinal inflammation, not the food itself. And intestinal inflammation reduces the expression of the histamine-clearing enzyme DAO, thereby worsening histamine intolerance. Cutting histamine foods manages the symptom, but it doesn’t lower the bacteria causing it. More on the actual fix in Tier 2.

NSAIDs, alcohol, medications

NSAIDs and alcohol directly damage the gut lining and disrupt tight junctions, independent of anything you’re eating. Nearly every medication affects the gut somehow: finasteride, cancer treatments, antidepressants, plenty of others. Some guts are just more sensitive than others. If symptoms started or worsened around when a medication started, that’s a variable to isolate like any food.

Antibiotic history

Recent or repeated courses are one of the most overlooked lines in a symptom timeline. Ask this before assuming diet alone caused the dysbiosis.

This is what messed up my gut over time. When you kill beneficial bacteria, it allows pathogens to grow. Not everyone’s guts bounce back to optimal after antibiotics.

Nutrient density over restriction

Zinc, magnesium, B-vitamins are cofactors for stomach acid, enzymes, glucose metabolism. Parietal cells need zinc to make acid at all. Oysters are the easiest, cleanest source. A deficient system reacts to foods a replete system handles fine.

Nutrient dense foods that are very easy to digest and unlikely to cause symptoms include liver, gizzards, dairy, eggs (yolk only) and oysters. Some starches like potatoes are also really nutrient dense if you tolerate it.

Always consume easy-to-digest, nutrient-dense foods that don’t cause inflammation. That’s how you rebuild your resilience buffer over time.

Natural ≠ optimal for you

Organic, unprocessed, “clean” says nothing about whether your gut handles it today. Stop asking “is this healthy,” start asking “does my system handle this cleanly right now.”

Behavior: size, speed, timing, posture

Eating fast and eating too much volume overwhelms capacity regardless of what’s on the plate. Either purposefully limit your portions or use something like chopsticks to eat slower. If you shovel your food too quickly, you will still feel hungry. If you wait 20-30min after your meal, you’ll feel the satiety kick in.

Eating hard to digest meals too close to bed can mess with your digestion. Lying down slows gastric emptying and transit time, allowing undigested food to feed pathogenic bacteria. This is often why people wake up feeling poisoned the next morning. Don’t lie down right after eating. If you do anyway, left side keeps the esophageal junction above the acid pool.

Milk, soft cheese and fruit are the exceptions here since they digest very quickly…depending on the portion size, of course.

Hydration is not just water

Electrolyte content and fluid variety matter for motility and stool quality. Plain water alone under-hydrates at the cellular level. Coconut water, milk (including kefir, yogurt, etc), fruit and bone broth are far superior. Add salt to make it even better.

A meal can be liquid only (bone broth/soup/milk/yogurt), so don’t think you have to “eat” a meal. Liquids can be a meal as well.

Too much liquid around a big solid meal can impair/slow digestion. Carbonated water/espresso/wine/beer (yes, even beer) can actually help to speed up digestion if not overdone.

Transit time, both directions

Beetroot/corn/activated charcoal test: eat cooked beets/corn (supplement AC), time the red/yellow/black color in stool. 12-24 hours is healthy. Over 30 hours is slow, bacteria get extra time to ferment and produce toxins. Under 12 hours is fast and this can lead to malabsorption of nutrients as well as low short-chain fatty acids due to reduced time to ferment.

How to fix slow transit time and constipation

The intestinal inflammation catch 22

Intestinal inflammation itself degrades digestive enzymes, lactase being the clearest case. This is how someone who tolerated dairy fine for years suddenly can’t. Also, when food sensitivities tend to get worse over time or developing new sensitivities you never had.

The enzyme deficiency is often downstream of inflammation, not its original cause. Fix the inflammation and tolerance sometimes returns without ever touching the enzyme directly.

Stress: 3 separate pathways

#1: Stress suppresses vagal tone, lowers HCl (stomach acid), digestive enzymes, and bile output before food even arrives. This leads to slow digestion → indigested food → intestinal inflammation and nutritional deficiencies.

#2: Chronic cortisol and sympathetic dominance cause direct mucosal damage, the same mechanism behind stress ulcers. Fix your food perfectly and pathway two can still be running.

#3: Chronic stress impairs the immune system which makes it easier for pathogens to grow.

Fixes:

• Sit down, breathe before the first bite, don’t eat mid-scroll or mid-argument (or too close after an argument if you’re still mad). Easy to digest foods like milk and honey will be beneficial, but try to avoid harder to digest, complex meals.

• Slow nasal exhale-biased breathing raises vagal tone directly, track resting heart rate to see what’s working.

• Ice cubes/pack to the face (especially the eyes) drops heart rate within seconds, useful before a meal you can’t avoid being stressed around.

• Morning light within the first hour blunts the exaggerated cortisol spike from artificial light alone; overcast sky still beats any indoor lighting by 20x.

• Magnesium acetyl taurate in the evening for GABA-glutamate balance.

• Acute stack for unavoidable stress: L-theanine 600mg, taurine 3g, magnesium acetyl taurate 2g. 1 cup milk + 1 heaped tbsp honey + 500mg-1g aspirin is my go-to.

Food and stress get most of you 80-90% there. But experimentation is slow, one variable, days of waiting, then the next variable. That’s the honest path and it works. It’s just slow.

Some of you will nail all of this and still be inflamed. Not a Tier 1 failure. A sign the problem moved somewhere food and lifestyle can’t reach alone: bile stuck in the wrong direction, a pathogen or fungal overgrowth running the show, enzyme output food can’t restore on its own, or in rarer cases something environmental. The rest of this article is how you find out which one is yours and compress months of guessing into weeks.

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Full article

To fiber or not to fiber, that’s the question.

Fiber might be the most polarizing macronutrient in health media right now, and almost nobody arguing about it has bloodwork and stool data to back up their side.

On the pro-fiber side alone, you’ve got at least three incompatible justifications.

• Tim Ferriss built the Slow-Carb Diet around legumes as an insulin-management tool, pure fat-loss mechanics, no detox framing at all.

• Karen Hurd, the self-styled “Bean Queen,” argues something almost unrelated: that soluble fiber’s real power is binding bile and sweeping excess hormones, toxins, and metals out through enterohepatic recirculation, a “toxic bile” theory that critics call a cleanse dressed up as biochemistry.

• And then there’s Dr. Will Bulsiewicz, the most mainstream of the three, who frames fiber’s benefit around feeding specific microbial “guilds” that strengthen with repeated exposure, with microbiome diversity as the master variable. Three prominent pro-fiber voices, three different mechanisms, not obviously compatible with each other.

On the other side, carnivore and animal-based advocates argue the opposite: that fiber is a gut irritant, not a gut savior.

• Paul Saladino built his original stance on plant defense chemicals, oxalates, lectins, phytates, causing SIBO and autoimmunity, though he’s since softened toward an animal-based model that still avoids beans, grains, and most vegetables.

• Shawn Baker is the sharper case study here, because he actually tried reintroducing fruit as an experiment, got gut irritation within days, and rather than treating that as data about his own dose or tolerance, updated toward “the food category itself is the problem,” a conclusion the rest of the carnivore world largely inherited from him.

• Steven Gundry sits somewhere in between, still eating plants but stripping them of lectins through pressure-cooking and peeling, proof the anti-fiber camp isn’t actually monolithic either.

Then there’s Ray Peat, whose online following has arguably gone further than Peat himself ever did. Peat’s actual target was never fiber as a category, it was specifically fermentable fiber and resistant starch, the kind that feeds bacterial overgrowth, which he traced through a chain of intestinal fermentation raising serotonin and endotoxin, which in turn suppress thyroid and progesterone while elevating cortisol, estrogen, and prolactin. His actual fix wasn’t elimination, it was substitution: raw carrot, cooked bamboo shoots, well-cooked mushrooms, chosen specifically because they sweep the gut without (much) fermenting. A far more surgical position than the “all carbs are safe, all fiber is poison” version his followers often run with.

Bulsiewicz, interestingly, offers the most useful concession in this whole debate: he acknowledges a “fiber paradox,” that the people whose guts need fiber most are also the ones who react worst to it initially, requiring graduated reintroduction rather than an all-or-nothing approach. That’s a structurally similar argument to the one this article is about to make, that a bad reaction to a food is real, but it isn’t automatically proof the food category is the enemy. It might be proof something else needs fixing first.

Almost none of these camps have run a controlled before-and-after GI-MAP, full stool metabolite panel, and matched bloodwork on themselves to check whether their theory actually holds up mechanistically. So I did.

I took a comprehensive gut and blood panel, went on a structured bean diet for several weeks, and ran the exact same panels again. Not a survey, not a theory, a single tightly controlled before-and-after, with numbers that either support one of these camps or they don’t.

The results support neither camp (as basically all my experiment results do). The results are more specific and more interesting than “fiber is good” or “fiber is bad.”

This isn’t a case for carnivore, and it isn’t a case for slow-carb.

It’s a case for looking at what actually happened at the microbial, metabolic, and hormonal level when fiber intake goes up, because the real story turned out to be a lot more conditional, and a lot more mineral-dependent, than any of the camps arguing about it seem to account for.

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The setup

Two GI-MAP stool panels with stoolOMX addon (which includes SCFAs and bile acids), three weeks apart.

The first was collected after using 100mg thymoquinone daily during a mixed diet around 10g fiber daily. Thymoquinone eradicated nearly all my bad bacteria (read the results here).

The second was after 3 weeks of eating 500-600g of chicken breast and 500g of black beans per day (around 50g of fiber a day). I chose chicken because it was low in iron and very low fat (to support fat loss). It didn’t help lower ferritin at all.

Two things to point out. The diet was very low fat (chicken breast and no added fat), which independently affects bile acid metabolism. Also, I stopped the experiment after 18 days instead of 21 days because I was experiencing a lot of air hunger. I suspect it’s because chicken is low in zinc and carnitine, which started to impair my energy metabolism. A later OAT showed that I was experiencing pseudohypoxia, which was likely caused by the thymoquinone. And this is why I stopped it. 2-3 days later after stopping the bean diet, my air hunger was gone.

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Myth 1: “Fiber increases SCFA production across the board”

This is the most basic pro-fiber claim, more fermentable substrate should mean more short-chain fatty acid output, full stop. It didn’t hold up.

Total SCFA output actually fell slightly by 14%. Within that total, the mix shifted: acetate dropped from 57.7% to 40.9% (newly flagged low). Butyrate rose from 15.3% to 25.7% and propionate rose slightly from 24.5% to 31.0%.

So more fiber substrate didn’t grow the total fermentation pool. It just reshuffled which SCFA dominated, and the pool overall shrank slightly.

So despite a 5x increase in fiber, total SCFAs didn’t increase.

A short but important correction: butyrate going up isn’t automatically a win

If you’ve spent any time in gut health content, you’ve probably absorbed one idea: butyrate good. Supplement it, ferment for it, chase it. It’s treated almost like a trophy number.

Here’s the piece almost nobody explains: butyrate isn’t a standalone nutrient you’re trying to maximize. It’s one of three major short-chain fatty acids, or SCFAs, byproducts your gut bacteria produce when they ferment fiber. The other two are acetate and propionate, and all three are made from the same process, by overlapping groups of bacteria, often from each other. Butyrate getting hyped as “the good one” misses that these three exist in a cooperative network, not a leaderboard.

Quick primer on what each one actually does.

Acetate is the most abundant of the three, and it functions as a circulating energy source for tissues throughout the body, including the brain. It’s also a raw material the liver uses to build cholesterol and other lipids, and it plays a role in appetite signaling through the hypothalamus.

Propionate travels to the liver and gets used as a substrate for gluconeogenesis (the process of building new glucose), and it has documented insulin-sensitizing and cardioprotective effects.

Butyrate is the one that gets all the attention because it’s the preferred fuel source for colonocytes, the cells lining your colon, and it has strong local effects on tightening the gut barrier and calming inflammation right where it’s produced.

All three matter. None of them is “the good one” in isolation.

Here’s the mechanistic detail that actually changes how you should read a butyrate number going up: acetate isn’t just a separate, competing SCFA. It’s often the literal raw material used to make butyrate. Certain bacteria break dietary fiber down into acetate and lactate first, and then a different set of butyrate-producing bacteria (Roseburia, Faecalibacterium prausnitzii, and Eubacterium are the main names here, along with Clostridium butyricum, a species increasingly used as a probiotic) consume that acetate as feedstock to synthesize butyrate. This handoff between bacteria is called cross-feeding.

So when you see acetate drop and butyrate rise on the same test, that’s not automatically two unrelated changes, one bad and one good. It can be the exact same carbon simply getting passed one step further down an assembly line, from acetate-producing bacteria to butyrate-producing bacteria. That’s a shift in which microbial guild is dominant, not necessarily evidence that your gut suddenly got better at fermentation overall.

That’s exactly what happened on my test: total SCFA output didn’t increase, it stayed roughly flat, while the internal ratio shifted, acetate down, butyrate up. If cross-feeding explains that shift, it’s evidence of a community rebalancing toward acetate-consuming, butyrate-producing bacteria, not evidence that my gut environment became healthier or more productive across the board. A rising butyrate number with a shrinking total pool is a different pattern, not an upgrade.

One genuine bright spot worth naming rather than dismissing: my free T3 rose from 4.2 to 5.2 pmol/L over this same window, and I noticed feeling subjectively warmer, even accounting for it being winter here. Butyrate has documented effects on enhancing thyroid hormone receptor sensitivity, meaning it can make your cells more responsive to the thyroid hormone you already have. So this may be one place where the shift actually paid off, even while the rest of the metabolic picture moved the wrong direction.

Myth 2: “Fiber increases bile acid excretion and lowers cholesterol via bile binding”

This is Karen Hurd’s entire framework, and it’s also the textbook mechanism most dietitians would cite for why soluble fiber helps cholesterol: fiber binds bile acids in the gut lumen, forcing more fecal excretion and forcing the liver to synthesize more bile from cholesterol, lowering serum cholesterol as a side effect.

My total bile acids fell by roughly 59%. Both primary bile acids and secondary bile acids dropped in absolute terms. The percentage split between primary and secondary stayed almost identical across both tests (99.5% secondary, 0.5% primary).

If fiber enhanced bile excretion, total bile would have increased, not decreased. Yes I did lower my fat intake, which does lower bile, but I was already on a low fat diet, so the decrease wasn’t huge.

The textbook mechanism didn’t show up at all. If anything, total bile acid turnover went the opposite direction, exactly the kind of finding that should give pause to a framework built entirely on fiber-driven bile excretion as a detox and cholesterol-lowering mechanism.

Myth 3: “More fiber means more diversity, which means a healthier gut, and feeds keystone species like Akkermansia”

This is closest to Bulsiewicz’s framework, and it’s also probably the most widely repeated pro-fiber claim in mainstream nutrition content right now: fiber feeds beneficial, diversity-supporting bacteria, including keystone mucin-associated species (aka Akkermansia).

Akkermansia muciniphila, one of the most talked-about “good” keystone species in gut health content, crashed roughly 15-fold. Meanwhile, several other commensals bloomed dramatically over the same window: Bifidobacterium up 15-fold, Faecalibacterium prausnitzii up 80-fold, Lactobacillus up 11-fold, and Escherichia 135 fold (not good per se). Bacteroidetes nearly tripled (though still under the reference range), and Firmicutes rose roughly 16-fold.

The Firmicutes:Bacteroidetes ratio rose from 0.02 to 0.15 which looks bad. But Firmicutes just increased faster than Bacteroidetes, and it’s likely that Bacteroidetes just needed more time to catch up.

Here’s a big objection people might have: someone will say I simply lacked dietary diversity, one fiber source (black beans), one protein source (chicken), plus milk, for an extended stretch wasn’t good enough. And that a wider variety of fiber types would have produced a cleaner, more Bulsiewicz-style outcome.

That’s a fair point to raise, but I don’t think it changes the outcome much. A wider variety of fermentable fiber sources still adds to the same total fermentable substrate load. It doesn’t guarantee that only “beneficial” bacteria will grow while it suppresses pathogenic/opportunistic bacteria.

Diversity of fiber type wasn’t the obvious missing variable here. Total load and directionality were.

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Myth 4: “Fiber selectively feeds good bacteria at the expense of bad ones”

This is arguably the most important myth to address directly, because it’s the one that would most cleanly validate Saladino and Baker’s anti-fiber position if the data supported it, and it’s also the one most pro-fiber advocates implicitly assume.

Neither clean story holds. Opportunistic and dysbiotic taxa didn’t just appear, they exploded, several from non-detectable to clearly flagged high:

• Bacillus up 19-fold

• Enterococcus faecalis

• Enterococcus faecium

• Pseudomonas spp.,

• Pseudomonas aeruginosa

• Fusobacterium spp. up 12,000-fold

• Streptococcus spp. up 3-fold

Pseudomonas aeruginosa and Fusobacterium spp. are powerful histamine producers. Toward the end of this experiment, my food sensitivities came back and I reacted more and worse to specific foods.

Also, for the first half of the experiment, I was having ghost wipes daily. Then the second half, it got worse. Which I correlate to intestinal inflammation.

On a positive note, Citrobacter spp., flagged high at 1.17e9 on the baseline test, dropped to non-detectable on the follow-up. Not every change here was bad.

What this did to immune surveillance, and the symptoms that came with it

Secretory IgA swung dramatically, from 2138 (flagged high) down to 262 (flagged low), a collapse in mucosal immune surveillance capacity over the same window the opportunist bloom occurred. Zonulin improved slightly (184.7 to 172.3) and calprotectin improved as well (63 to 40), so this wasn’t a uniformly worse inflammatory picture, but the IgA collapse is hard to ignore given what else was happening.

One plausible mechanism is that several of the bloomed bacteria, particularly Enterococcus and Streptococcus species, are known to secrete IgA-specific proteases as an immune-evasion strategy. This breaks down IgA, thus lowering it.

It’s possible that my overall IgA production was good, but couldn’t keep up with enhanced breakdown.

This tracked with real, felt symptoms: histamine issues and skin flares specifically when eating high-histamine or fermentable foods like garlic and onion, the kind of reactivity pattern that fits an opportunist-driven, IgA-compromised gut environment.

The metabolic markers: no clean win here either

If beans and fiber were doing what the conventional narrative promises, blood sugar and lipid markers should have moved cleanly in the right direction. They mostly didn’t.

• Cholesterol: 5.6 to 5.5 mmol/L

• LDL: 3.8 to 3.7

• HDL: 1.3 to 1.1

• Triglycerides: 3.07 to 2.73 (likely because I lowered my fat intake a bit)

• hs-CRP: 0.8 to 1.7 mg/L (likely due to the pathogenic bacterial growth)

• Fasting insulin: 4.7 to 6.0 mIU/L

My fasting insulin increased after I swapped from a high GI to a low GI carb…

This is worth sitting with, because it directly contradicts the popular “slow-digesting carbs like beans are better for blood sugar control” claim central to Ferriss’s framework specifically. Insulin didn’t improve.

The part that actually matters day to day: it didn’t even work for weight

I never lose weight when I eat beans. The whole fat loss premise of the slow-carb diet is that you don’t have to weigh your food or track your calories. Don’t get me wrong, beans/lentils are very satiating. My goal was to eat 750g of beans per day (250g per meal). But I couldn’t do more than 500g.

Yet, despite eating 2000 calories, I just couldn’t drop weight. And it has happened every time in the past as well.

I know it works for other people, but it doesn’t for me. My theory is that endotoxin and histamine-producing bacteria increase. This causes mitochondrial dysfunction and impairs energy metabolism. Making it impossible to lose weight. My hsCRP increased and my fasting insulin increased. Coincidence? I think not.

There is a case study of a morbidly obese man had about 35% of his gut microbiota dominated by an endotoxin‑producing Enterobacter cloacae B29 strain (R). After 23 weeks on a whole‑grain, prebiotic‑rich “WTP” diet (no antibiotics), this Enterobacter abundance fell to undetectable, and he lost 51.4 kg (174.8 kg → 123.4 kg), with marked improvements in hyperglycemia, hyperinsulinemia, hypertension, and fatty liver.

When they implanted this bacterium into mice, it induced obesity and insulin resistance on a high‑fat diet but not on normal chow, showing that this endotoxin‑producing bacterium can causally drive diet‑dependent obesity and metabolic dysfunction…if the diet allowed it to.

The practical takeaway isn’t “never eat beans.” It’s a dose and frequency question. It works for some and doesn’t work for others. For me, it increased a lot of inflammatory endotoxin and histamine-producing bacteria. This causes inflammation, which causes swelling and water retention and insulin resistance (not severe…just worse).

I’m just showing what happened to me when I did it.

Why this happened: the mechanistic read, and where Peat’s framework actually fits

Putting this together, the fiber load appears to have overwhelmed the system’s selective fermentation capacity rather than cleanly feeding “good” guilds at the expense of “bad” ones. This is closer to Ray Peat’s actual position than to either the Bulsiewicz or Saladino/Baker framing, since Peat’s specific focus was always fermentable fiber and resistant starch, the kind that feeds bacterial overgrowth and drives endotoxin and serotonin up, not fiber in general.

The bloom of Enterococcus, Streptococcus, Fusobacterium, and Pseudomonas alongside a genuine drop in mucosal IgA fits his endotoxin-driven cascade better than it fits either pro-fiber camp’s predictions.

The testing-limitation question, and what “actually fixed” would even mean

Now I have to be honest/clear here.

On my previous stool test it looked like thymoquinone eradicated almost every single pathogen I had. The best thing ever. Now I still stand by that.

However. Just because a stool test doesn’t pick up a pathogen doesn’t mean it’s not there. It only shows that current shedding is below the test’s detection threshold at that specific moment. Levels could genuinely be low, just behind biofilm or too low to be detected in a stool test. So how would anyone ever know they’ve genuinely resolved a gut issue, rather than just caught it on a good day?

The honest answer is: repeat testing without having to follow an elimination diet just to keep symptoms at bay.

What “fixed” actually means, and why almost nobody testing this is telling you the truth

A carnivore advocate can claim they solved their gut issues. The moment they add potatoes back in, their gut explodes again.

Everyone’s gut dysfunction has a different root cause, which means everyone needs a different temporary intervention. You can fix gut issues: a structured elimination phase, targeted antimicrobial support where indicated (thymoquinone, in my case), and a period of easy-to-digest, nutrient-dense, non-inflammatory foods while the terrain stabilizes. Then you reintroduce and retest.

Test → adjust → test → adjust → build resilience → fixed.
You can’t do it without repeat testing.

Every time a gut guru said they cured gut issues, I wonder if they are still on an elimination diet and what they current stool test looks like. Because almost all of them has never done repeat testing and they are all just managing it with an elimination diet.

The same applies to vegan, paleo, autoimmune paleo, or whatever protocol is trending this month. All of them remove a broad food category and call the resulting relief a fix. None of them, on their own, cure anything. The only way to know if something’s actually fixed is to reintroduce the trigger and retest, which is exactly what almost nobody selling a protocol is willing to do publicly.

What’s changing in the protocol going forward

A few adjustments based directly on what this data showed:

Acacia fiber, 1 tbsp x3 daily. A slow fermenter, chosen specifically to target acetate recovery without the same rapid, indiscriminate bloom risk beans presented. As far as I know, no one has used this dose and done a stool test, so we’ll likely learn something new from what acacia does. Maybe acacia is one of those unique fibers that doesn’t allow pathogens to grow.

C. butyricum and L. reuteri. To increase butyrate and keep inflammation low. They are also great for increasing other beneficial bacteria (think diversity).

Thymoquinone, reintroduced at 10 drops. It killed all my pathogens last time, but I didn’t use a fiber last time, so it killed my Bacteroides and Firmicutes as well. It didn’t create resilience, which is why I added the acacia. It’s still the best pathogen killer out there (for me).

Pregnenolone reduced from 300mg to 100mg, with PEA added (600mg x3 daily). I want to see if it will help to increase 5-alpha reductase (5AR) and allopregnanolone; so that I don’t need as much pregnenolone just to keep allopregnanolone optimal.

Methylene blue (20mg) and MitoQ (20mg) reintroduced. My NADH increased after removing MitoQ and thymoquinone likely made everything worse without MitoQ, so I want to see if MitoQ can offset it. I also want to see how a high-ish dose of methylene blue will affect my mitochondria and energy metabolism.

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TL;DR

• Tested it: Ran two full GI-MAPs (with SCFA/bile acid add-ons) and matched bloodwork, three weeks apart, before and after 18 days of ~500-600g chicken breast + 500g black beans daily (~50g fiber/day, up from ~10g).

• Total SCFA output fell 14%, despite a 5x jump in fiber intake. More fiber ≠ more SCFAs. Just a shift in what you have.

• Butyrate rising isn’t automatically good news: especially if it’s at the expense of other beneficial SCFAs.

• Bile acids fell 59% overall: if fiber helped with bile excretion, then total bile would have increased or at least stayed the same. And my cholesterol would have dropped a lot more. And if you think a 0.1 is good after 3 weeks, then you need to update your expectations of things that are far superior.

• Akkermansia crashed 15-fold while other commensals (Bifido, Faecalibacterium, Lactobacillus, E. coli) bloomed 10-135x. Some beneficial bacteria increased…but in conjunction with harmful/inflammatory/pathogenic bacteria.

• Opportunists exploded across the board: Bacillus, Enterococcus faecalis/faecium, Pseudomonas spp./aeruginosa, Fusobacterium (12,000x increase), Streptococcus. Fiber didn’t selectively feed good bacteria over bad (contradicts both pro- and anti-fiber camps’ clean narratives).

• Pseudomonas aeruginosa and Fusobacterium are established histamine producers, which explains the return of food sensitivities and worsening reactions to garlic/onion late in the experiment.

• Secretory IgA collapsed (2138→262), plausibly from IgA-protease-secreting opportunists degrading surveillance faster than it could be replenished, not just reduced production.

• Metabolic markers mostly got worse: hsCRP up (0.8→1.7), fasting insulin up (4.7→6.0)… directly contradicts the “slow carbs are better for blood sugar” claim central to the Slow-Carb Diet.

• No weight loss, despite amazing satiety and a caloric deficit, I didn’t experience fat loss. Likely due to enhanced inflammation from endotoxin/histamine-producing bacterial overgrowth.

• Best-fit framework: Ray Peat’s, not because he’s right about everything, but because his specific target (fermentable fiber/resistant starch → endotoxin/serotonin → hormonal suppression) matches the data better than Ferriss, Hurd, Bulsiewicz, or Saladino/Baker’s positions. At least for me.

• The bigger point on “curing” gut issues: most gut gurus claiming to have cured gut issues have never repeat-tested, and they’re managing symptoms through permanent elimination, not fixing anything. Real resilience means retesting under reintroduction and challenge, not a single clean snapshot.

• Protocol going forward: acacia fiber (slow fermenter, targeting acetate recovery), C. butyricum + L. reuteri, thymoquinone reintroduced alongside fiber this time (to avoid wiping out commensals without building resilience), reduced pregnenolone + added PEA, reintroduced methylene blue and MitoQ.

How to fix your gut

Here’s how to get start to fix your own gut:

• Ultimate symptom checklist (connecting your symptoms to root causes is the start, always)

• Quick gut reset

• Ultimate guide on how to fix your digestion

Most people who test cortisol are testing:

• the wrong thing,

• at the wrong time,

• in the wrong medium,

…and drawing conclusions the data was never built to support.

Cortisol is made in the zona fasciculata of the adrenal cortex from cholesterol via the usual pregnenolone → 17‑hydroxyprogesterone → cortisol pathway.

Cortisol is created on demand and not stored. Cortisol is the highest in the mornings and peaks about 30 minutes after waking; the waking cortisol response. This is meant to help you feel more alert and awake. If morning cortisol is blunted, people often experience morning fatigue and need lots of coffee to wake them up.

So just testing first thing in the morning tells you nothing about:

• your daily rhythm

• free cortisol

• how your body is metabolizing and excreting it

So I’m going to explain to you blood tests, salivary testing and urinary testing of cortisol and the pros and cons of them all.

#1 Blood Testing: A Single Snapshot of Total Cortisol

A standard serum cortisol draw is almost always ordered first thing in the morning, timed to catch the cortisol awakening response 30 to 60 minutes after you get up. That’s the peak of your entire daily curve. It’s the single easiest moment to get a high number, and it’s the only moment most labs ever look at.

Two problems with this.

It’s one data point on a curve that matters as a curve. Cortisol isn’t supposed to sit at one level. It should spike on waking and decline steadily through the day into a low trough at night. A blood draw tells you where you were at 8am. It tells you nothing about whether you crash by noon, spike again in the evening, or never come down at all. Two people can have an identical morning number and completely opposite daily rhythms, and blood testing cannot tell them apart.

It doesn’t separate free from bound cortisol. Roughly 90 to 95% of circulating cortisol is bound to corticosteroid-binding globulin (CBG) and, to a lesser extent, albumin. Bound cortisol is inactive. It’s cargo, not signal. Only the free fraction is biologically active at the tissue level. A standard serum test measures total cortisol, bound and free together, so it cannot tell you whether your active cortisol is actually high, or whether CBG levels (which shift with estrogen status, inflammation, and liver function) are just carrying more inactive hormone around. You can have high total cortisol with normal free cortisol, and a blood test will not distinguish them.

This is why blood cortisol is useful for ruling out extremes (frank Addison’s or Cushing’s) but close to useless for the kind of dysregulation most people actually have.

Symptoms commonly attributed to high cortisol, for reference, since this is what usually sends people looking for a test in the first place:

• Abdominal fat gain disproportionate to overall weight

• Face and neck fat redistribution (”moon face,” fat pad at the back of the neck)

• Muscle loss and thinning skin, especially on the arms

• Poor sleep, especially waking at 2-4am and not falling back asleep

• Anxiety, irritability, and a wired-but-tired feeling

• Elevated resting heart rate and blood pressure

• Blood sugar dysregulation and increased sugar cravings

• Poor wound healing and easy bruising

• Suppressed libido and reproductive hormone output

• Reduced immune function, frequent illness

Notice that almost every one of these is also a symptom of low cortisol, thyroid dysfunction, or a dozen other things. Symptoms alone tell you to test. They don’t tell you what the test will show.

#2 Salivary Testing: The Rhythm, Closer to the Truth

Salivary cortisol fixes the biggest problem with blood testing. Because saliva only contains the free, unbound fraction of cortisol (bound cortisol doesn’t cross into salivary glands), a salivary panel is a much closer proxy for biologically active cortisol than a serum total.

And because you collect multiple samples across the day, typically waking, mid-morning, afternoon, and bedtime, you actually get the diurnal curve instead of one point on it. This is the test that can show you a flat curve, a delayed peak, a blunted awakening response, or a cortisol level that refuses to drop at night.

Cortisone-to-cortisol ratio. Some salivary cortisol tests will include the cortisone (inactive) to cortisol (active) ratio. This reflects 11-beta-HSD2 enzyme activity, which converts active cortisol into inactive cortisone. That enzyme runs on NAD as a cofactor, which makes this ratio a usable proxy for cellular NAD/NADH redox status. A skewed ratio isn’t necessarily an adrenal problem. It can be a mitochondrial and redox problem. And NAD can be low due to chronic inflammation and DNA damage.

However, salivary cortisol is still not the full picture. Saliva only shows you what makes it into saliva. It doesn’t tell you anything about total cortisol production, how much cortisol your body is actually clearing, or what happens to cortisol after it’s been secreted. You get the shape of the curve. You don’t get anything about downstream metabolism.

If you can only run one test, this is the one I’d pick. Best cost-to-insight ratio, easiest to run at home, and it directly answers the question most people actually care about: is my rhythm doing what it’s supposed to do.

#3 Urinary Testing: How Your Body Is Actually Processing Cortisol

This is where it gets genuinely interesting, and where most people’s understanding of cortisol testing stops entirely.

A comprehensive urinary panel, collected across four to five points over 24 hours, gives you the diurnal free cortisol rhythm just like saliva does. But it adds an entirely different layer: metabolism and clearance.

Cortisone-to-cortisol ratio. Same as salivary, but this time in urine, so processing is a bit different. It’s good to compare the two, but they should be relatively similar.

5-alpha and 5-beta reductase metabolites of cortisol (5A-THF and 5B-THF). 5AR doesn’t just convert testosterone to DHT. It also deactivates cortisol.

These numbers tell you which enzymatic pathway your liver is using to clear cortisol into its terminal metabolites, and how efficiently it’s doing it. This is clearance information that blood and saliva simply cannot provide, because clearance happens downstream of secretion, in the liver, and only shows up in what gets excreted.

And this is why when people tend to use finasteride, they end up with higher cortisol, due to impaired clearance of cortisol.

DHEA, DHEA-S, and 17-OHP is included because they are also created in the adrenals. Pregnenolone feeds both the cortisol pathway and the DHEA/androgen pathway, and 17-OHP sits at the branch point between them. You cannot properly interpret cortisol output in isolation from these, because a shift in one changes substrate availability for the others.

The practical upshot: urinary testing tells you not just how much cortisol you’re making and when, but how well you’re clearing it, and what that says about liver function, redox status, and the shared hormonal pathways cortisol doesn’t operate in isolation from.

Why HuMAP Is the Most Comprehensive Option

If you’re going to run one comprehensive test, a HuMAP-style multi-point urinary panel is the one to pick, because it puts cortisol in context with the rest of the steroid tree rather than testing it as an island. The pregnenolone → progesterone → allopregnanolone pathway can help to offset elevated cortisol. Your androgens (testosterone, DHT, androstenedione, and their 5-alpha/5-beta metabolites) are the main cortisol blockers. 5-alpha reductase is just as important at clearing cortisol as it as creating allopregnanolone, androsterone and DHT.

This matters because the ratios between these pathways are often more informative than any single absolute value. A cortisol number in isolation tells you cortisol is high or low at the specific point in time. The same number in the context of your androgen pool, your progesterone metabolites, and your 5-alpha:5-beta split across all three steroid classes tells you which specific enzymatic step is upregulated or downregulated, and therefore what to actually do about it. That’s the difference between “your cortisol is off” and “your hepatic 5-alpha reductase capacity is being consumed by something else, and here’s what.”

My Own Data: A Working Example

I’ve run several HuMAP panels on myself over the past year, and my own cortisol picture is a good illustration of why this matters.

My free cortisol daily rhythm is genuinely textbook. It peaks on waking at 35 ng/mg creatinine and declines appropriately through the day down to 2 at bedtime. If you only looked at the rhythm, you’d call it optimal, and you’d be right.

My cortisone-to-cortisol ratio sits at 0.37, comfortably inside the 0.18 to 0.60 reference interval, which reflects healthy 11-beta-HSD2 activity and, by extension, decent cellular NAD/NADH redox status.

But my total metabolized cortisol came back at 1910, against a reference interval of 2600 to 7200. Below range.

Taken together, my cortisone is broken down adequately, but my cortisol’s metabolism by 5AR and 5BR is low. This puts my overall metabolized cortisol under the reference range.

On a lesser panel, that number alone would read as adrenal underperformance, and someone might reach for adrenal support or hydrocortisone. The rhythm and the ratio data say otherwise. Adrenal output and rhythm are intact. What’s actually happening is that I’m using 500-600mg of testosterone enanthate per week, and cortisol shares hepatic 5-alpha and 5-beta reductase capacity with the “big-ish” androgen load my liver is processing. The enzymes are busy. Cortisol is competing for clearance capacity, not failing to be produced. My 5A-THF:5B-THF ratio came back at 0.76, upper third of the 0.19 to 0.82 reference range, which is optimal. This is competitive substrate inhibition at the liver, not a cortisol production problem, not thyroid, not pathological reductase activity.

None of that distinction is visible on a blood test. A single morning serum draw would have caught my cortisol at or near peak, looked completely normal, and told me nothing about the hepatic throughput problem sitting underneath it.

The pregnenolone-to-allopregnanolone side of the same panel made a similar point. Allopregnanolone started at the floor of its reference range, a predictable consequence of exogenous testosterone suppressing pregnenolone → progesterone synthesis. After adding 300mg of pregnenolone to my protocol specifically to restore that pathway, allopregnanolone came back at 5.0 on a follow-up panel, against a reference interval of 0.8 to 6.4.

And to have to take 300mg of pregnenolone just to have high-normal allopregnanolone is also not right. So it’s likely again that testosterone is saturating the 5AR enzyme and not a lot of progesterone and cortisol can be metabolized through it.

The Practical Recommendation

If you can run all three, do it. Blood rules out the extremes and is often what your doctor will order anyway. Saliva gives you the rhythm cheaply and repeatably, which is useful for tracking change over time. Urinary, ideally a comprehensive HuMAP-style panel, gives you the full metabolic and cross-pathway picture that actually explains why a number is where it is.

If you can only run one, run salivary. It’s the best single upgrade over standard blood work for the least cost and effort, and it directly answers the question most people actually have, which is whether their daily rhythm is intact.

If you want the whole picture, the one that tells you which specific enzyme or pathway to actually address rather than just confirming a number is off, HuMAP is the test. It’s the only one of the three that will tell you the difference between “your cortisol is low” and “your cortisol is fine and something else entirely is eating your clearance capacity.”

Knowing your number is only half the job. Below, I break down what's actually driving cortisol up in the first place, from the specific micronutrient deficiencies most people never test for, to the metabolic, hormonal, gut, and lifestyle factors that keep the HPA axis stuck "on."

Then I walk through exactly how to bring it back down, mechanism by mechanism: the supplement stack I use to restore the GABAergic pathway your HuMAP can actually measure, the circadian and training interventions that move the needle without another supplement, which adaptogens are worth using short-term and why, and the small, unusual levers (carbs with salt, aspirin, caffeine timing) that most people never hear about because nobody explains the mechanism behind them.

Want to know what your symptoms (and labs) are actually telling you? A personalized Health Report takes your existing symptoms (and labs) and turns them into a clear, prioritized action plan, built on your data, not population averages. Get it here.

Ask Hans is trained on everything I’ve tested, written, and protocolled → mechanism first, no fluff. Available 24/7 for members. Check it out here.

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It’s probably one of the most common recommendations in health today.

CoQ10. PQQ. MitoQ. Thymoquinone. NAD boosters. Red light therapy. Creatine.

The assumption is always the same:

Your mitochondria aren’t working properly, so give them more support.

The problem is that “poor mitochondrial function” isn’t a diagnosis.

It’s the equivalent of saying your car is slow.

Is the engine missing spark?

Is there no fuel?

Is the turbo broken?

Is the exhaust blocked?

Is the gearbox slipping?

The symptom is identical.

The solution isn’t.

Every mitochondrial supplement promises better energy. Very few ask the more important question: which part of energy metabolism is actually broken?

Earlier this year I discovered I had a bottleneck recycling NADH back to NAD. My organic acid testing showed elevated lactate, elevated β-hydroxybutyrate, elevated alanine and a collection of metabolic backup pathways all trying to compensate.

MitoQ almost completely normalized the pattern.

That raised a question.

If thymoquinone is also a quinone (another electron acceptor) would it produce the same result?

So I did something most people probably shouldn’t.

I took 100 mg of pure thymoquinone every day for four weeks and repeated the same testing.

I expected similar results.

Instead I accidentally produced an entirely different type of mitochondrial dysfunction.

What surprised me wasn’t that thymoquinone behaved differently.

It was that almost every marker initially looked like the same problem.

• Elevated NADH.

• Elevated ketones.

• Elevated lactate.

• Poor energy production.

Yet the root cause was completely different.

One pattern represented a simple bottleneck in electron transport.

The other represented oxidative damage shutting down key enzymes inside the Krebs cycle.

The symptoms looked almost identical.

That’s what this article is really about.

Not whether thymoquinone is “good” or “bad.”

It’s about learning how to distinguish different forms of mitochondrial dysfunction, understanding why supplements marketed for “mitochondrial support” are not interchangeable, and why throwing random compounds at your mitochondria without identifying the specific bottleneck first is often nothing more than educated guesswork.

And I’ll also show you what I’d do differently if I had to do it again…because it truly had amazing benefits for my gut. Read more about that here.

Here’s the full TLDR of what happened during thymoquinone supplementation:

Starting condition

Underlying CoQ10 bottleneck → MitoQ withdrawal → NADH accumulation → ↑ reduced intracellular environment

↓

Phase 1: Initiation

100 mg thymoquinone → increased redox cycling in an already highly reduced state → semiquinone formation → superoxide generation → oxidative damage to iron-sulfur enzymes (especially aconitase and SDH)

↓

Phase 2: Metabolic switch

SDH inhibition → succinate accumulation → HIF-1α stabilization (pseudohypoxia) → PDK activation → PDH inhibition + glycolysis upregulation → pyruvate can no longer efficiently enter the TCA cycle

↓

Phase 3: Compensation

Pyruvate overflow → lactate, D-lactate and alanine production → glucose oxidation falls → glycolysis becomes the primary ATP source → protein breakdown + glutaminolysis increase to sustain ATP → glutamate, GABA, ammonia and orotic acid all rise as downstream consequences. Thymoquinone recycling NADH, thus keeping glycolysis going.

Now let’s discuss all the nitty gritty juicy bits.

The Marker That Started All of This

My fasting finger-prick lactate was always on the higher side. Never over the reference range, but consistently high enough that I suspected something specific: an elevated NADH to NAD ratio, even at rest.

It did matter if I ate high carb or low carb, mega-dosed B-vitamins, etc. Nothing seemed to move it.

In an overnight fasted OAT (organic acid test), my urinary lactate and BHB (ketone body) were also elevated over the reference range, suggesting I had elevated NADH, even after an overnight fast.

I then decided to do an OAT 60 min post-workout after drinking about 1.5L of milk with 50g of glucose powder. No supplements. This was to see what my energy metabolism looks like under stress and to see where things would break.

Here are the poor NADH recycling markers that matter:

• BHB (ketone): 263.1 H (reference ceiling: 116.4).

  • When NADH is high, acetoacetate is converted to BHB to regenerate NAD.

    

• Lactate (created from pyruvate): >889.3.

  

• D-lactate: >200.0.

  • It’s produced through the methylglyoxal pathway, which activates when glycolytic intermediates back up so severely that they spontaneously convert to methylglyoxal. Methylglyoxal is then detoxified through the glyoxalase system, yielding D-lactate. This pathway only kicks in when the system is deeply over-reduced, when regular lactate production isn’t enough to keep pace with NADH excess.

• Alpha-hydroxybutyric acid (α-HB): 114.9 (15.4-95.6)

  • Produced when alpha-ketobutyrate is reduced by LDH under high NADH conditions.

    

• Alanine (created from pyruvate): 1069.9 H, nearly 2.5x the upper limit.

• Krebs cycle itself: fumarate and malate were both piled up (39.1 H and 30.3 H respectively).

Meaning, oxaloacetate was converted to malate to help recycle NADH back to NAD via the malate-aspartate cycle instead of converting to citrate.

In summary, almost every single backup enzyme that recycles NADH back to NAD was massively upregulated to compensate for the primary factor necessary → CoQ10.

I never thought I’d have a CoQ10 problem because I eat a lot of red meat, which is a great source of it.

So given that CoQ10 was flagged on the test, I supplemented it as the next experiment.

MitoQ Fixed It Completely

MitoQ, 20mg daily, six weeks. This is a synthetic analog of your own native coenzyme Q, permanently tagged with a molecule that concentrates it 500–1000x inside the mitochondrial matrix. It’s built to slot cleanly into the electron transport chain your body already knows how to run. In essence, it helps the electron transport chain run flow better, leading to less reactive oxygen species production and better ATP production.

It worked. Here’s how the markers changed:

• BHB: 263.1 → 8.7.

• Lactate: >889.3 → >267.7 (70% decrease).

• D-lactate: >200 → 29.5 (85% decrease).

• Alpha-hydroxybutyric acid (α-HB): 114.9 → 44.1

• Alanine: 1069.9 → 237.1

The Krebs cycle pattern completely inverted → fumarate and malate normalized.

Every marker representing poor NADH to NAD conversion improved. Bottleneck type one, solved.

Part Three: Testing a Claim That Turned Out to Be Wrong

There’s a claim that gets repeated constantly in supplement circles: quinones (vitamin K2 MK4, PQQ, lapachone, thymoquinone, etc) are broadly interchangeable as electron acceptors, and any quinone can regenerate NADH back to NAD the way CoQ10 does. If that were true, thymoquinone should have behaved like a CoQ10.

So I tested 100mg thymoquinone daily, four weeks, no MitoQ during this window. To my surprise (and maybe deep down what I expected), NADH markers shot up, some even higher than before the mitoQ experiment.

• BHB: 8.7 → 324 H (highest yet)

• Lactate (for some reason they couldn’t measure this one, it came back blank)

• D-lactate: 29.5 → >200

• Alanine: 1069.9 → 237.1 → 583.9 H (not as high as before, but definitely higher)

• Glucose: 87.5 → 45.9 → 3.2 (this is explained by less glucose intake (no glucose powder around the workout))

• Pyruvate: 7.7 → 21.8 → 130.8 H (despite lower glucose intake, pyruvate was the highest yet. This indicates glycolysis was running harder than before with less glucose intake than before)

• Alpha-hydroxybutyric acid (α-HB): 114.9 → 44.1 → 109.6

Basically the same after before mitoQ. I could have assumed that this is simply impaired NADH recycling like before, but here’s what made me think twice.

Succinic acid came back at 893.0 H → roughly 3.4x the upper limit, and about 44x higher than my MitoQ result.

Here’s what stood out to me.

• High cis-aconitic acid and low isocitrate (converted by aconitase)

• High succinic acid and low fumarate (converted by succinate dehydrogenase)

Both enzymes have iron-sulfur clusters, which are sensitive to oxidative stress. So this pattern generally demonstrates elevated oxidative stress.

The problem is, succinic acid in high amounts acts as a signalling molecule. It stabilizes a protein called HIF-1α (hypoxia inducible factor 1α); the same signal your body uses to sense low oxygen, except oxygen wasn’t the problem.

This is called pseudohypoxia. As if you’re not getting enough oxygen, while you are. So you can start to feel out of breath and your endurance goes to shit. Exactly what happened to me.

HIF-1α then switches on an enzyme that shuts down pyruvate dehydrogenase (PDH), the gatekeeper that lets pyruvate enter the mitochondria in the first place, called pyruvate dehydrogenase kinase (PDK).

What happens is you end up with high pyruvate (which I had) and low citrate (which I had). Basically, you can’t use the glucose you have. And now the pyruvate is converted to alanine and lactate to compensate and regenerate NAD. It’s essentially a broken energy system.

The mitochondria (TCA cycle) is about 15-fold more efficient at creating ATP than glycolysis. You create only 2 ATP per glucose molecule if pyruvate doesn’t enter the mitochondria. But if pyruvate can enter, now you create ≈ 30–32 ATP per glucose molecule.

So creating ATP through glycolysis is a very wasteful system.

My best explanation for where this started: thymoquinone is a quinone and an electron acceptor, but not the same kind of quinone as MitoQ. MitoQ is built to accept and hand off electrons cleanly, keeping the electron transport chain flowing without hiccups.

Thymoquinone is an alternative electron acceptor, which can accept 2 electrons. If it accepts 2 electrons, it becomes thymohydroquinone, which is a powerful antioxidant. If it only accepts 1 electron, it forms an unstable intermediate called a semiquinone radical. And instead of finishing the handoff cleanly, that intermediate can hand its electron to oxygen instead, generating superoxide, a free radical.

Superoxide then damages the iron-sulfur clusters, inhibiting proper flow of the TCA, causing isocitrate and succinate to build up → inhibiting PDH → inhibiting pyruvate uptake into the mitochondria → increasing L- and D-lactate, which poisons the cells even more.

What happens when you can’t burn glucose

You burn muscle instead.

With succinate dehydrogenase blocked, succinate backed up and stabilized HIF-1α → the same signal your body uses to sense low oxygen, even though oxygen wasn’t the problem.

HIF-1α did two things at once:

It shut down pyruvate dehydrogenase, and it switched on the genes for glycolysis itself, the classic hypoxia fallback. Glycolysis makes a small amount of ATP without ever touching the mitochondria, but it only works if NADH keeps getting converted back to NAD; normally the mitochondria’s job. Locked out of that route, the cell used lactate dehydrogenase instead: pyruvate gets reduced to lactate, NAD regenerates, glycolysis keeps running. That’s the direct explanation for both my sky-high pyruvate (glycolysis’s output, pooling up with nowhere to go) and my L- and D-lactate (the exhaust from the workaround keeping glycolysis alive).

Running glycolysis flat-out needs a constant glucose supply, so my body broke down protein (evident by elevated α-Aminoadipic acid) to keep feeding it, partly via gluconeogenesis (building new glucose in the liver), which is why alanine, the molecule that shuttles nitrogen from muscle to liver for exactly that job, was so elevated.

That same protein breakdown dumps amino acid nitrogen onto alpha-ketoglutarate, forming glutamate, which is why it nearly quadrupled. This is the identical entry point tumor cells use to run glutamine as fuel (glutaminolysis): glutamine → glutamate → alpha-ketoglutarate → forward into the cycle.

More glutamate meant more raw material for GABA, made directly from it. And GABA’s own clearance route feeds back into succinate (the same clogged step) so it couldn’t clear either. Meanwhile my glutamine-to-glutamate ratio dropped, pointing to glutaminase releasing free ammonia faster than it was being mopped up, and with more ammonia arriving than the urea cycle could process, orotic acid (the overflow valve for that exact bottleneck) spiked to 3.5x its ceiling.

In summary: SDH block → succinate → HIF-1α → glycolysis up, PDH down → protein burned to keep glycolysis fed → glutamate, GABA, ammonia, and orotic acid all rising as downstream consequences of the same starting event.

The Actual Lesson

There are many things that can inhibit mitochondrial function:

• Nutritional deficiencies (vitamins and minerals)

• Heavy metals

• Environmental toxins

• Plastics

• Cortisol/stress

• Low thyroid

• etc.

Learning to spot different patterns helps you better identify the root cause and to do the right protocol to address it.

So it becomes a case of pattern recognition.

Using 100mg of thymoquinone can be seen as:

But even a failure is a win. Because you always learn something, especially pattern recognition.

First test I learned the poor NADH recycling pattern. Test 2 (mitoQ) proved my theory. Test 3 (thymoquinone) looked like another NADH recycling problem, but then exposed the elevated oxidative stress, succinate buildup and hypoxia inducing dysregulation of cellular energy metabolism.

You can read all the studies you want, which will help with pattern spotting, but this is one step further to truly see how your body operates with different compounds. And how it can break under various scenarios. And what’s causing it and how to fix/prevent it.

This is the part that matters more than any single compound verdict: you cannot tell these two apart from how you feel, and you often can’t tell them apart from generic bloodwork either.

• My hsCRP stayed under 1 through the entire thymoquinone month, showing my inflammation was very low.

• My 8-OHdG, a direct marker of oxidative DNA damage, came back below detection, same as it did on MitoQ.

Both are fairly systemic, downstream readouts, and neither is especially sensitive to damage localized to one specific enzyme complex inside the mitochondrial matrix. The only way I caught the difference was by looking at exactly which intermediate was piling up, and exactly which one wasn’t.

“Support your mitochondria” isn’t a strategy. It’s a guess dressed up as one. The actual question is always: which specific step is stuck, and why. Same symptom, different disease, different fix.

Because you can throw something at your mitochondria that is supposed to work, but if you don’t test, you’ll never know. And that compound might even backfire and cause damage.

What’s a safe dose then? And how to do it right.

PQQ, MitoQ, and thymoquinone get marketed under the same “mitochondrial support” umbrella, but they’re not interchangeable, and understanding what each one actually does is the whole point of this series.

PQQ builds more mitochondria and helps with NADH/NAD recycling. PQQ is a great compound, but it doesn’t fix any root cause issues people might have, such as a vitamin, mineral or CoQ10 deficiency. It helps to increase NAD by converting lactate back to pyruvate, using NADH and creating NAD. It also upregulates complex I of the ETC, so in theory, it should have worked for me. But since my bottleneck was CoQ10, upregulating complex I didn’t do anything, but you still need CoQ10 for things to flow. So NADH remained high.

MitoQ restores flow through the existing engines. It’s a synthetic analog of your own native coenzyme Q, permanently tagged to concentrate 500–1000x inside the mitochondrial matrix. It slots cleanly into the electron transport chain your body already runs, directly improving how efficiently electrons move through Complex I and III and get handed off to oxygen. This is what actually fixed my NADH backup. This addressed my specific root cause problem.

Thymoquinone does neither of those jobs. It doesn’t restore electron flow through the ETC. It can help to regenerate NADH, but via the NQO1 enzyme. This doesn’t affect the ETC flow. It can help to mop up free radicals, but it doesn’t improve the flow of the ETC or ATP production, if the core issue is poor flow.

Used together, this is a genuinely complementary stack rather than three competing options:

• PQQ helps create new mitochondria, upregulate complex I and keep lactate low. This improves energy metabolism a lot given everything else is in check already.

• MitoQ keeps the existing capacity running clean (proper ETC flow and APT production)

• Thymoquinone potently stimulates NRF2, which upregulates a whole host of antioxidant enzymes, protecting the cells and allowing them to work better.

The mistake isn’t using thymoquinone. It’s assuming its mechanism overlaps with MitoQ’s, or dosing it as if it were as forgiving as MitoQ’s targeted, native-mimicking chemistry.

Why Thymoquinone Specifically Becomes a Problem

Thymoquinone is a redox-active quinone, which means it can pick up and hand off electrons very well and then hand them off to:

• NADH/NADPH-dependent enzymes (E.g. NQO1)

• glutathione

• oxygen, which then creates superoxide (a free radical)

• free transition metals like copper and iron, which then create the highly toxic hydroxyl radical

That last part matters. When thymohydroquinone (its reduced form) encounters free copper (Cu²⁺) or iron (Fe²⁺), it becomes a genuine pro-oxidant, generating damage through Fenton-type chemistry (hydroxyl radical) rather than neutralizing anything.

Once superoxide had already disabled the iron-sulfur clusters in aconitase and succinate dehydrogenase, that damage releases free iron into the surrounding environment, which is exactly the metal this chemistry needs to keep itself going. It’s a plausible feed-forward loop, not two separate problems.

It also doesn’t repair anything upstream. An enzyme called NQO1 converts thymoquinone using NADH and NADPH into thymohydroquinone, regenerating NAD or NADP as a byproduct in the process.

That NAD then allows glycolysis to convert more glycogen/glucose into pyruvate to generate ATP. In a state where HIF-1α has already shut off pyruvate dehydrogenase and switched glycolysis into overdrive as the fallback fuel source, handing that pathway a fresh supply of NAD doesn’t nudge the system back toward normal oxidative metabolism. It helps excessive glycolysis, similar to the Warburg effect in cancer cells. Thymoquinone can look like it’s supporting energy production while actually reinforcing the exact dysfunctional state that’s already in place, rather than resolving it.

Thymoquinone has potent cellular protective properties (e.g., Nrf2 upregulation), improves mitochondrial function, and has potent anti-cancer properties. But it’s in low doses. The bigger the dose, the more it will start to negatively affect normal cells as well.

Dosing, and What I’d Do Differently

The best available long-duration human data comes from a phase I trial of a standardized black cumin oil delivering roughly 10mg of actual thymoquinone per day for 90 days, with good tolerance and modest positive effects. Toxicology-derived safety modeling puts a conservative ceiling around 48.6mg/day for adults. I ran 100mg/day (roughly double that conservative ceiling, and ten times the dose used in the one long-duration human trial) as isolated, pure thymoquinone rather than whole black seed oil, which likely produces a faster, higher peak tissue concentration for a given total dose than the same amount delivered in a slower-absorbing oil matrix.

I don’t regret taking 100mg. It did real, measurable work on my gut that nothing else in thirteen months of testing managed. And I’d rather know the metabolic cost precisely than not have taken it and never found out what it could do.

But I wouldn’t run that dose again without guardrails, and I wouldn’t run it long-term at all.

Short-term only. Four to six weeks, then step down or stop. This is inferred from my own timeline. I don’t know whether this pattern would have shown up sooner or worsened further past six weeks.

Pair it with MitoQ. My NADH did skyrocket after stopping mitoQ. And the more NADH accumulates, the harder thymoquinone has to work to compensate, which can create lots of ROS.

Consider pairing with DCA (dichloroacetate) to keep PDH switched on. Dichloroacetate directly inhibits PDK, the enzyme HIF-1α uses to shut pyruvate dehydrogenase off. If the goal is preventing that specific shutdown cascade, DCA is the most direct countermeasure available; it’s sold without a prescription, but it’s not without real risk of its own; peripheral neuropathy is a documented concern with sustained high-dose use. 1-2g depending on how much you need. Do finger prick lactate testing to see if it prevents the increase in lactate or not.

High-dose thiamine (B1) is worth considering alongside it. Thiamine pyrophosphate is PDH’s required cofactor. If DCA is keeping the enzyme switched on, making sure it has abundant cofactor supply is a logical complement. Gram-level doses directly stimulate PDH activity, separate from thiamine’s normal nutritional role. Thus forcing even more pyruvate oxidation.

I want to be clear about the limits of all of this: this is one person’s dataset, at one dose at one specific point in time. My baseline mitochondrial function, my particular redox environment and enhanced need for CoQ10 could have altered the results, but none of that is guaranteed to generalize.

Plenty of people will run 100mg of thymoquinone and feel nothing but the benefits. But it was a high dose relative to the available human trial data, and the fact that it went this sideways for me is reason enough for anyone considering it to treat it with real caution rather than assuming “natural” means “forgiving.”

What I’m Testing Next

I’ve since restarted MitoQ at 10mg a day, and I expect my mitochondrial markers to normalize on the next OAT. I’ll report that when it’s back.

On the gut side, I’m now testing whether coconut oil affects 5-alpha reductase activity, with a stool test, HuMAP panel and a comprehensive fatty acid panel alongside it.

I doubt lauric acid will have any effect on my 5AR activity.

An in vivo animal study found coconut oil had no measurable effect on serum or tissue DHT, possibly because lauric acid gets oxidized for fuel too quickly to accumulate the way longer-chain fatty acids do.

I’m more interested in seeing what it does to my gut and fatty acid composition.

On the hormone side: I’m dropping my pregnenolone dose from 300mg to 100mg in preparation for the next experiment (glycine). 300mg pregnenolone took my allopregnanolone from 0.7 to 5.0 on a 0.8–6.4 scale, which is perfect. My wife did notice I’m calmer and in a better mood since increasing my dose.

The reason I’m testing glycine is that I doubt I need 300mg of pregnenolone just to have normal levels of allopregnanolone. So I suspect my conversion of progesterone to 5-alpha progesterone is suboptimal. And glycine has been shown to enhance that conversion through glycine receptor activation.
So stay tuned for those results.

Some people are using it as a DHT booster:

Bro creatine literally raises your DHT by 56%, that’s basically finasteride in reverse.

Others think it’s a scam:

The creatine-DHT thing comes from ONE study. Fifteen years ago. Rugby players. N=20. Nobody has replicated it. Everyone quoting “56% increase in DHT” is quoting a single small trial like it’s settled science.

Others use it entirely for health:

Creatine is genuinely one of the most slept on longevity compounds. Bone density, brain fog, memory in older adults, less sleep needed to recover. This isn’t a bro supplement anymore. This is a lifespan supplement.

Same molecule. Three completely different conversations happening about it at the same time, and almost nobody running all three at once, on themselves, with a lab to check.

One camp is terrified creatine is quietly wrecking their hairline. Another camp is dismissing that fear as one small 2009 study that’s never been replicated. A third camp has moved on entirely and is treating creatine as a bone density and brain longevity compound for aging women and seniors, backing it with 2026 systematic reviews and a genuinely different research literature than the one the hair-loss crowd is arguing about.

All three of these people are talking about the same 5 to 15g of white powder. None of them are looking at the same data.

I ran the actual experiment. 45 grams a day, two weeks, full urinary hormone panel before and after, compared against two other hormone interventions I’d already run using the exact same testing methodology. Not a blood draw. Not a single DHT number in isolation. The entire androgen pool, the entire estrogen pool, the cortisol pathway, and the methylation markers underneath all of it.

Here’s what I found. And here’s why, by the end of this article, you’ll understand that a testosterone-and-DHT blood panel is kindergarten science. It tells you almost nothing about what’s actually happening to your hormones.

(Here’s why I prefer urine hormone testing over blood testing)

The One Study Everyone’s Arguing About

There’s exactly one study, from 2009, showing creatine raises DHT. Sixteen rugby players. 25 grams a day for a week, then 5 grams a day for two more weeks. DHT up 56% after the loading phase, still 40% above baseline three weeks later.

That’s it. That’s the entire foundation for a fear that’s kept a meaningful chunk of the lifting population off one of the cheapest, most effective, most heavily studied supplements that exists.

Twelve other studies have looked at creatine’s effect on testosterone, at doses from 3 to 25 grams, for up to 12 weeks. Ten found nothing. Two found small, non-significant increases. Five of those studies also checked free testosterone specifically. None of them found anything there either.

Then, in 2025, someone finally ran a cleaner follow-up. 5g a day. Blood work. DHT: flat.

So now you have one small trial from 2009 showing a real jump, and one more recent trial at a lower dose showing nothing. Nobody has reconciled the gap. I had a theory: what if it’s dose-dependent, and 5 grams simply never crosses whatever threshold 25 grams did.

So I went further.

What I Actually Did

45 grams a day, two weeks. Not because there’s a study behind that number…there isn’t. My thinking was that if 25g increased DHT, but 5g didn’t, what would 45g (3 tbsps) do?

I did this as a 3rd experiment in my ongoing DHT and hormone series, using the same multi-point urinary panel (HuMAP).

• 1st was 100mg Thymoquinone + skullcap (both which can supposedly inhibit 5AR)

  • Results here

• 2nd was Butea Superba + 100mg pregnenolone + methylated B-complex

  • Results here

• 3rd is with 45g creatine + 300mg pregnenolone

The Androgen Pool. Here’s what happened

Why One Number Isn’t Enough

Testosterone and DHT are two data points in a pathway with a dozen active intermediates. DHEA-S adds a third, but it’s still just checking the starting material without seeing what happens to it on the way to the finish line.

The androgen pool is the sum of everything that pathway produces → DHEA, DHEAS, androstenedione, testosterone, DHT, and their downstream metabolites (androsterone, etiocholanolone, 5-alpha and 5-beta androstanediol, and more), each reflecting a different enzyme step along the way.

A blood test showing “testosterone: normal, DHT: normal” can look identical whether your body is converting precursors efficiently and clearing metabolites normally, or whether it’s quietly rerouting production through a completely different pathway, bottlenecking at one specific enzyme, or shifting the alpha/beta balance in ways that never touch the two numbers you actually measured.

Two people with identical T and DHT blood values can have completely different things happening one or two steps upstream or downstream and only the fuller metabolite panel shows you which one you’re looking at.

Results

(thymoquinone + skullcap → Butea → creatine)

• DHT (ng/mg Creat/Day): 12 → 5.6 → 11 (a 96% increase from Butea, but likely a restoration to my baseline)

• T:DHT Ratio: 13.3 → 23.2 → 11.8 (most due to a restoration of my baseline)

• Androsterone (ng/mg Creat/Day): 2430 → 1420 → 2760 (94.4% increased from Butea and a 13.6% increase from the 1st test)

• Total Androgen Pool (ng/mg Creat/Day): 6,578.9 → 3,953.5 → 5,912.8 (up 49.6% from my prior low point)

The interesting thing is that my DHT didn’t increase over baseline, but my androsterone did. More on that in a bit.

Where the Signal Actually Comes From

A ratio between two downstream metabolites can hide the real story if both shrink or grow together. I learned this the hard way analyzing my Butea data and had to walk back an earlier conclusion. The fix is tracking substrate-to-product conversion directly, not comparing two end-products to each other.

The backdoor pathway → DHEA to androstenedione to androsterone to DHT, no testosterone required, is where this shows up clearest.

Pre-creatine: androstenedione at 1.6, androsterone at 1420. Conversion multiple: 888x.

Post-creatine: androstenedione at 1.0, androsterone at 2760. Conversion multiple: 2,760x.

The best conversion efficiency across all three tests I’ve run.

T to DHT tells the same story. On the prior test, testosterone fell 18.75% but DHT fell 53.3%.

Given that androstenedione:androsterone increased by 211% and T:DHT decreased by 49.1% after creatine (showing enhanced 5AR activity), this almost certainly shows that Butea lowered 5AR.

What Didn’t Move

DHEA+DHEAS kept falling across all three tests: 240, then 74, then 56. It never recovered.

I don’t have a clean explanation yet. Butea also lowered my DHEA-S on blood tests, but I’m not sure why it kept dropping after removing Butea. Creatine doesn’t have any (known) DHEA lowering effects. So it’s possible that this is due to residual Butea effects that needs to work itself out over time.

The Estrogen Trade

I was using Skullcap with my first test, which is a powerful aromatase inhibitor. So estrogen getting “worse” isn’t bad. It just reverted to baseline, which is still optimal.

• Total estrogen pool: 28.29 → 21.14 → 24.52. (Up 16% from my low point. Not a big deal, since it’s not overpowering my androgen pool)

• E2 (estradiol): 4.6 → 4.8 → 5.8 (climbing across all three tests. Test 1 was with Skullcap, which is one of the most powerful aromatase inhibitors I’ve used, so that explains the increased. It doesn’t concern me)

• T:E2: 34.8:1 → 27.1:1 → 22.4:1. The worst ratio of the series. Again, not a concern as the ratio is still optimal.

Creatine has no established aromatase mechanism, so the increase in E2 is expected. E2 technically didn’t increase. It just went back to baseline without an aromatase inhibitor present.

Estrogen Methylation

2-M-E1:2-OH-E1 and 2-M-E2:2-OH-E2 (the markers showing how efficiently your body clears catechol estrogens through COMT) both peaked during my prior test and dropped back down here.

Creatine synthesis is one of the largest consumers of SAMe in the body. Supplementing exogenous creatine should theoretically reduce that internal demand and free up methylation capacity elsewhere, including COMT. The data didn’t cooperate, but I know exactly why.

I was running a methylated B-complex during the prior test and wasn’t running it during this one. That B-complex was doing direct, active methylation support. Creatine’s contribution is real, but indirect and smaller in comparison. Pull the direct support, and the ratio falls, even with a legitimately methyl-sparing compound sitting in its place.

Here’s how it changed.

This means that I might benefit from higher B-vitamin intake. Either supplement a B-complex or eat more liver.

The 5-Alpha, 5-Beta Split That Doesn’t Match

Cortisol metabolism shifted toward 5-beta across 3 tests. So did my progesterone metabolites, even as I raised pregnenolone to 300mg. As I increased my pregnenolone dose, my allopregnanolone increased, but my 5AR/5BR ratio decreased (explained below).

While my androgen-specific 5-alpha marker moved toward 5AR dominance.

5-alpha reductase isn’t one enzyme. The isoforms sit in different tissue with different substrate preferences. It’s plausible hepatic clearance is being pushed toward the higher-throughput beta route by the sheer pregnenolone load, while something separately favors alpha conversion specifically in androgen-producing tissue. My allopregnanolone, meanwhile, went from low to optimal across the same window. Whatever the ratio says, the metabolite I actually care about landed where it needed to.

Why This Split Matters (The “Escape Valve” Explanation)

5-alpha reductase isn’t one enzyme. Two isoforms exist (SRD5A1 and SRD5A2) and they sit in different tissue: liver, prostate, skin, brain. A urine panel’s “5-alpha vs. 5-beta” marker is really the combined output of separate enzymes.

That’s why cortisol, progesterone, and androgens can move in opposite directions in the same two weeks. Corticosteroids and progestins run largely through liver clearance. 5-beta is the escape valve for getting steroids out of circulation fast. Androgens destined for actual activity (DHT acting on prostate, skin, hair) go through a more selective, capacity-limited 5-alpha route tied to tissue-specific conversion, not bulk clearance.

My theory: tripling pregnenolone from 100mg to 300mg flooded the system with substrate, and the liver’s bulk-clearance pathway (5-beta) scaled up to handle it. The escape valve doing its job, not 5-alpha being inhibited. Meanwhile, in tissue where androgens actually convert to DHT, 5AR was enhanced.

Why a DHT Blood Test Is Kindergarten Science

Here’s the actual point of this entire article.

If I’d run a standard blood panel, total T, DHT, maybe estradiol, I would have seen exactly one thing: DHT normalized (or went up after the Butea experiment). That’s the entire finding a typical panel gives you. It’s the finding the hair-loss forums are arguing about, and the finding the 2009 and 2025 studies both limited themselves to.

What that panel would have missed entirely:

• What happened to the entire androgen pool

• The backdoor pathway

• Androstenedione to androsterone ratio

• Testosterone to DHT ratio

A blood test will tell you only the last one. Pretty useless IMO.

It wouldn’t tell you the rest. Or whether methylation capacity moved (it didn’t, and a standard panel would never have shown you why not, because it doesn’t test methylation ratios at all).

Whether the 5-alpha shift was universal across steroid classes or isolated to androgens specifically (it was isolated → cortisol and progesterone moved the opposite direction, a finding no blood test panel I’m aware of would ever surface).

A DHT blood number is a single frame from a movie. It tells you where a marker landed. It tells you nothing about the conversion efficiency that got it there, what it cost elsewhere in the system, or whether the same intervention is quietly doing the opposite thing to a different steroid pathway one enzyme family over. Anyone still forming an opinion on “does X raise my hormones” from a single T and DHT number is answering a much smaller question than the one that actually matters.

What I’d Do With This

If you’ve experienced hair loss from creatine, swap to another form. Often creatine monohydrate causes gut issues for some people, which causes inflammation and hair shedding. Swapping to creatine HCL often solves that problem.

If you’re avoiding creatine purely on forum panic, you’re skipping one of the most evidence-backed, safest supplements in existence over the weakest possible evidence base → a single study most people citing it have never actually read past the headline number.

What I’d test next, if I had access to this panel and wasn’t trying to find a ceiling: baseline hormone panel before starting, then retest at a standard 5g/day maintenance dose after 6-8 weeks. My 45g protocol was built to find the edge of the effect, not to model what a normal dose does to a normal user.

What I can (relatively) conclusively say is that creatine doesn’t increase testosterone to DHT ratio. But it does seem to stoke the fire of the backdoor pathway converting more androstenedione into androsterone. That seems relatively undeniable in my results.

Apart from that, it didn’t really have any other hormone effects.

But the goal isn’t simply to take it for hormonal effects. It has a shit ton of other benefits.

The Other Reasons to Actually Take This

• Endurance and recovery: noticeably higher training volume tolerance with less fatigue, faster bounce-back between sessions.

• Cognitive performance: sharper idea generation, easier creative output, improved mental clarity, likely tied to increased brain energy availability.

• Reduced need for sleep to recover: creatine lowers adenosine buildup, the molecule responsible for sleep pressure, meaning some people feel more recovered on less sleep.

• Bone density and frailty prevention: recent meta-analyses (2024, 2026) show real benefit for aging muscle, bone parameters, and fall/fracture risk when paired with resistance training, increasingly relevant for older adults and postmenopausal women, not just lifters.

• Cognitive protection in aging: 2026 systematic review data (over 1,500 participants) suggests benefit for memory, attention, and processing speed in older adults specifically.

• Ejaculatory control: blunted hypersensitivity, longer performance, faster recovery from overstimulation.

• Kidney and liver markers: unaffected even at extreme megadose, provided you check the right markers (Cystatin C over creatinine, since creatinine gets artificially inflated by creatine intake and muscle mass).

• No sleep disruption: contrary to the methylation-overload theory some people cite, tracked sleep data showed no deep sleep or REM impairment even at 45g/day.

• Cost and safety profile: one of the cheapest, most heavily studied supplements that exists, with three decades of safety data behind it. A track record almost nothing else in the supplement aisle can match.

Want to know what your own labs are actually telling you? A personalized Health Report takes your existing labs and turns them into a clear, prioritized action plan, built on your data, not population averages. Apply here.

Ask Hans is trained on everything I’ve tested, written, and protocoled → mechanism first, no fluff. Available 24/7 for members. Check it out here.

Most people would recommend switching to white meat if you want to lower ferritin.

If your ferritin or transferrin saturation comes back elevated, the advice you’ll hear almost everywhere is the same: cut red meat, cut organ meat, switch to chicken and fish. It feels intuitive. Less iron going in should mean less iron in the body.

It’s also wrong, and I’ve now proven it wrong on myself twice, in opposite directions.

The premise everyone gets backwards

Chicken breast is genuinely low in iron. Nobody disputes that. But whether a food actually helps you lower your iron status has almost nothing to do with how much iron it contains in isolation.

What matters is the ratio of zinc to iron in what you’re eating, because zinc and iron compete for the same absorption transporter in the gut, DMT1. Flood the gut lumen with zinc relative to iron, and you meaningfully blunt how much iron actually gets absorbed, almost regardless of how much iron is technically sitting on the plate.

Chicken breast has a zinc-to-iron ratio of roughly 1.4:1. That’s not disastrous, but it’s mediocre, and its absolute zinc density is low to begin with. So switching to chicken specifically to bring iron down doesn’t just fail to fix the problem, it can actively work against you, because you’re simultaneously starving your zinc status without doing much for the ratio that actually controls iron absorption.

Proof, in the direction nobody expects: my oyster experiment

Here’s an experiment that still surprises people when I describe it. I ate roughly 15 oysters a day for 30 days on top of extra red meat. My total iron intake came out to around 55mg a day, nearly 700% of the RDA. By any “eat low-iron foods” logic, this should have made my ferritin worse.

It dropped from 579 to 339 in that single month.

The reason is the ratio, not the absolute number. My zinc-to-iron ratio during that period was roughly 2.7:1, because oysters are extraordinarily zinc-dense, about 45mg zinc per 100g against just 6mg iron. Compare that to an earlier period when I was eating almost exclusively beef heart, where my ratio sat around 0.4:1, iron-dominant, and ferritin climbed instead, despite beef heart itself not being a particularly extreme iron source.

Here’s the ratio across a range of common foods, so you can see how this actually plays out:

Shellfish & Seafood

• Oysters: 7.5 : 1

• Shrimp: 2.6 : 1

• Squid: 2.1 : 1

• Salmon: 2 : 1

• Cod: 2 : 1

• Mussels: 0.3 : 1

• Clams: 0.08 : 1

Land Meats

• Pork (loin): 2.7 : 1

• Lamb: 2.1 : 1

• Beef (lean ground): 1.8 : 1

• Bison: 1.2 : 1

• Chicken (breast): 1.4 : 1

• Turkey (breast): 1.1 : 1

Eggs & Organs

• Eggs: 0.7 : 1

• Liver (beef): 0.6 : 1

• Kidney (beef): 0.7 : 1

• Heart (beef): 0.4 : 1

A few things jump out immediately. Chicken breast, the default “safe” choice for lowering iron, is very low in iron, but if you consume it as your main protein source, your zinc intake is also quite low.

Clams and mussels, despite being “seafood,” are some of the worst options on this entire list, iron-heavy relative to zinc despite feeling like a light, healthy choice. And oysters aren’t just good, they’re in a category of their own (most superior).

In essence, if you want to:

• increase your iron/ferritin, eat mussels, clams, liver and heart.

• maintain your iron, eat red meat and chicken breast (although even this might be enough to increase your ferritin).

• lower your ferritin, stick to lamb, pork loin, shrimp and oysters.

One more nuance worth flagging: ratio isn’t the whole picture. Shrimp, squid, cod, and salmon all have favorable ratios on paper, but their absolute zinc content per 100g is low. That means they’re fine to include, but you don’t want them to be the foundation of an iron-lowering strategy, because there’s simply not much zinc there to do the competitive-absorption work you need. The same logic applies to chicken breast twice over: a mediocre ratio and low density, stacked together.

The real-time failure: my recent chicken and bean experiment

I’ve now watched the inverse mistake happen in real time, on myself, deliberately. During a recent diet experiment, I switched from beef to chicken specifically as a strategy to bring iron down, alongside a bean-based fiber protocol and 4mg/day of supplemental copper.

The result: my transferrin saturation went from 26% to 75% over that period, while ferritin stayed essentially flat, 334 to 339 µg/L. The copper I was supplementing was doing exactly what copper does, mobilizing stored iron into circulation via ceruloplasmin and hephaestin, but without enough zinc in the system to help regulate or clear that mobilized iron, it just moved iron around rather than helping me actually offload it.

My serum copper itself didn't rise despite direct daily supplementation, going from 13.4 to 12.3 µmol/L, and ceruloplasmin stayed completely flat at 21 mg/dL, still below the reference range on both tests. Meanwhile my plasma zinc actually dropped further, from 112.7 to 102.5 µg/100mL, likely due to chicken breast being a horrible source of zinc and the phytic acid in the black beans also binding to the little bit of zinc available.

This is, as far as I can tell, a genuinely underexplored idea: that the entire “eat low-iron foods to lower ferritin” strategy is built on a flawed premise. It’s not about how much iron you eat. It’s about what you eat it alongside. This is also, I’d argue, part of why so many people with elevated ferritin end up leaning entirely on blood donation as their only lever, because dietary strategies built around avoidance rather than ratio management mostly fail, and donation becomes the only thing that seems to move the needle, slowly, every 2-4 months, forever.

The hidden cost nobody accounts for: what chicken-heavy eating does to zinc status

Here’s where this compounds into something worse than a failed iron strategy. If you switch to chicken specifically to lower iron, you’re not just failing to fix the ratio, you’re also actively under-feeding your zinc status, and zinc has direct consequences for testosterone that have nothing to do with iron at all.

There’s a controlled trial, Prasad et al. (Nutrition, 1996), that’s about as clean as this kind of human data gets. Healthy young men had their zinc intake experimentally restricted for 20 weeks. Mean serum testosterone dropped from roughly 39.9 nmol/L to 10.6 nmol/L, a 73% decrease. In related work, older men who were marginally zinc-deficient were supplemented with 30mg zinc gluconate daily for six months, and their testosterone rose from roughly 8.3 to 16.0 nmol/L, nearly doubling.

Read that again: a testosterone crash of that magnitude took 20 weeks of restriction, not 20 years. That matters here specifically because someone who switches to a chicken-heavy diet (or even fish) to manage iron, without realizing chicken is also a poor zinc source, could be inadvertently tanking their testosterone within months, on top of failing to actually fix their original problem.

I want to be precise about what is and isn’t proven here. There’s no study tracking someone eating a chicken-forward, zinc-marginal diet for years and drawing a clean line to a specific hormonal crash point. That extrapolation is mine, built on the biology, not a citation.

What is real: the KORA-Age study found high rates of subclinical micronutrient deficiency in older adults (52% low vitamin D, 27% low B12, 11% low iron, 8.7% low folate), associated with chronic disease and worse functional outcomes, and broader reviews show older adults commonly fall short of RDA targets for several minerals through diet alone.

Layer on top of that a cultural pattern: protein in general has been quietly demonized for years thanks to the saturated fat scare that got bundled in with red meat specifically, and a lot of people already default to small portions of protein overall, with chicken and egg whites as the “safe” choices when they do eat it. Someone actively avoiding red meat to fix their iron just adds another layer on top of an already zinc-marginal starting point.

Apps like Cronometer can tell you exactly what’s in your plate today. They have no memory of the months of chicken-forward eating that got you here, or why you started eating that way in the first place. Check my full article on the shortcomings of Cronometer here and what to do about it.

Not sure where your own iron, zinc, or testosterone status actually sits? Ask Hans can help you think through your specific symptoms and bloodwork in real time. Or if you want a full breakdown of your own hormone, mineral, and gut markers mapped against everything in this article, get a Personalized Health Report built specifically around your data.

Everything above this line is the philosophy and the data. What follows is the specific, practical protocol: the methods that actually move ferritin and iron status, ranked by what’s produced the clearest results, in myself and in the research.

You’re the exception, not the rule

I know exactly what pushback this gets, because I get it constantly: “I’ve eaten chicken breast for iron management for years and my testosterone is fine.” Fair, and I’m not going to tell you that you’re wrong or secretly deficient without knowing it. Individual variance in zinc requirement is real.

Absorption efficiency differs meaningfully from person to person. Gut health, detoxification load, genetics, and half a dozen other variables shift how much zinc someone actually needs to stay in range. Someone with excellent absorption and low baseline requirements can genuinely do fine on a diet that would deficiency someone else within a few years.

That’s exactly why this article isn’t a claim that chicken-heavy eating crashes testosterone in everyone. It’s an argument against assuming you’re in the clear just because you feel fine right now, and in favor of testing rather than guessing.

A good illustration of how large this individual effect size can be: I know of a case where a guy on a beef-heavy diet ran testosterone in the 700s ng/dL. He switched his primary protein source to salmon. Six weeks later, his testosterone had dropped to 306. He switched back to beef, and it returned to the 700s.

What it is a strong example of, is just how sensitive some individuals’ androgen production can be to protein source for reasons that may have nothing to do with iron at all, and everything to do with the low absolute zinc density salmon provides regardless of its favorable ratio. Ratio and density are two different variables, and this case likely implicates density more than ratio.

How to actually lower iron

My top 8 methods of how I dropped my ferritin from almost 600 to 180 without blood donations are discussed below. 👇

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Men’s health forums call it a DHT booster. Supplement companies market it as “nature’s finasteride reversal.” I recommended it myself, in my own DHT article, as one of the best libido-boosting herbs I’ve ever used.

Here’s the problem: there is essentially one small human trial ever showing that real Butea superba raises androgens. One.

And after two rounds of urinary hormone testing on myself, I’m now fairly convinced that most people, myself included, have never actually taken the herb the hype is built on.

I’m not here to tell you Butea superba doesn’t work. I’m here to show you what happened when I tested it properly, and why I now think almost nobody selling it on the market today is selling the real thing.

The Promise

The case for Butea superba goes something like this: it’s a Thai tuber, traditionally used for male vitality, and it supposedly works by stimulating 5-alpha reductase, the enzyme that converts testosterone into DHT, the more potent androgen responsible for libido, drive, confidence, and body composition.

The positive human data that exists is thin but real: a small trial gave 15 male volunteers 540mg/day for 7 days and found elevated endogenous steroids and LH throughout treatment. That’s it. That’s the foundational human evidence for an entire supplement category.

Everything else is anecdote, forum testimonials, and a single, often-cited case report of a man whose DHT reportedly spiked dramatically while using it, nearly doubling into territory well above the normal range, alongside reports of hypersexuality.

I wanted to know if this would replicate in my own body, with lab-verified data. So I tested it.

What I Actually Did

I ran two separate rounds of comprehensive urinary hormone testing (HuMAP → multi-point daily collection covering estrogens, androgens, progesterones, and corticoids), roughly two weeks apart, as part of my ongoing self-experimentation series.

Test 1: Post Skullcap (a compound I’d already confirmed as a genuine aromatase inhibitor in prior testing) as the primary intervention. Full article here.

Test 2: Post Butea superba (800mg/day, from Based Supplements → more on why I chose them below) plus 100mg pregnenolone daily, with skullcap removed.

Same person. Two weeks apart. Full urinary hormone panels both times. This wasn’t a guess based on how I felt; this was lab data, before and after, on the exact same testing methodology.

Also, here’s why urinary testing is superior to a blood test for 5AR and DHT.

Why I Chose This Supplier

I didn’t pick Based Supplements randomly. Their version 2 product came with an actual sourcing video → their team went to Thailand, filmed the harvest region, pulled roots directly out of the ground, and cut into them on camera to show the characteristic red sap bleeding from the root. This is the kind of visual verification most supplement companies never bother with. If authenticity in this category was going to exist anywhere, I expected it here.

So take note: this is, by all appearances, one of the more legitimate sourcing efforts in the category. And my results were still negative.

What the Data Showed

Here’s the comparison that matters. Skullcap phase vs. Butea + pregnenolone phase:

Testosterone: 160 → 130 ng/mg Creat/Day (down)

DHT: 12 → 5.6 ng/mg Creat/Day (a 53.3% decrease… and back within the “normal” reference range, from previously above it)

T:DHT ratio: 13.3:1 → 23.2:1 (a 74.4% increase)

DHEA + DHEAS: 240 → 74 ng/mg Creat/Day (the single biggest mover in the entire panel — a 69.2% drop)

Total androgen pool (T, DHT, A4, EPI-T, AN, OHAN, 5A-AD, 5B-AD, ET, OHET, DHEA, DHEAS combined): 6,578.9 → 3,953.5 ng/mg Creat/Day… a 39.9% decrease

Total estrogen pool: 28.29 → 21.14 ng/mg Creat/Day combined… a 25.3% decrease

T:E2 ratio: 34.8:1 → 27.1:1 (still favorable, but a 22.1% decline)

If Butea superba is supposed to be a DHT booster, this is close to the opposite of what happened. DHT fell. DHEA collapsed. The entire androgen pool contracted.

Ruling Out the Obvious Explanations

Before you assume this is “just a bad response,” I want to walk through what I checked and ruled out, because the honest answer here is more complicated than a single clean mechanism.

Was it beta-sitosterol inhibiting 5-alpha reductase? Beta-sitosterol is present throughout Butea plant material, and it’s a known partial 5-AR inhibitor (the same mechanism behind saw palmetto). But if 5-AR itself were being inhibited, I’d expect my androsterone:etiocholanolone ratio (the marker for systemic 5-alpha vs 5-beta reductase preference) to shift toward 5-beta. It didn’t. It went from 0.94 to 1.0… essentially flat. That rules out enzyme inhibition as the primary driver. The more likely explanation is substrate limitation: less total precursor pool (DHEA collapsed) feeding into the conversion, producing less DHT downstream, without the enzyme itself being touched.

Was it skullcap that was secretly suppressing DHT all along, and removing it should have helped? No. This data actually clears skullcap’s name further. DHT was elevated in the test where skullcap was present, and dropped in the test where it was removed and Butea was added. If skullcap had been the real DHT suppressor, removing it should have made DHT normalize upward, not fall further.

Did my thyroid function decline and drag everything down with it? No, my free T3 actually rose during this window (5.2, compared to my typical ~4.7), which should support androgen output, not suppress it. DHT dropping despite an improving thyroid picture rules out a systemic/internal explanation and points back toward something exogenous: the product itself.

Does this explain why testosterone itself dropped, not just DHT? Honestly, not fully. This is the loose thread I won’t pretend to have tied up. The DHEA/androsterone mechanism explains the broader androgen pool contraction well. It doesn’t cleanly explain why total testosterone itself also declined. I’d rather tell you that than force a tidier story than the data supports.

The Real Problem: Nobody Might Be Selling Real Butea Superba

Here’s where this gets bigger than my own n=1 experiment.

According to Nootropics depot, they have tested (actual plant identity testing, using chloroplast markers (rbcL, psbA-trnH) and a nuclear ITS2 marker) every Butea Superba on the market, including Based Supplements.

And here’s what they found: 100% chloroplast match to Butea monosperma, a different species entirely, with only 85.05% identity to a Butea superba reference on the ITS2 marker, compared to 96.24% identity to monosperma. Not a “nearest neighbor” call. An exact match to a complete monosperma plastid genome.

Their claim was blunt: almost nobody in this supply chain is testing for species identity, only for contaminants. Suppliers ship monosperma, brands sell it labeled as superba, and nobody checks.

This matters enormously, because Butea monosperma’s documented research history runs in almost the opposite direction of what the supplement market claims. Butin, isolated from monosperma seeds, is a documented weak estrogen with uterotrophic effects at a fraction of its anticonceptive dose. Extracts have shown estrogenic activity specifically on the ERβ receptor. This is a species with an antifertility and estrogenic research tradition, not an androgen-support one.

If what’s actually circulating under the Butea superba label is largely monosperma, a result like mine (DHEA and DHT both falling) isn’t an anomaly. It’s exactly what you’d predict.

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But What About the Positive Case Report?

You might be thinking: if genuine Butea superba is fake or absent from the market, how do we explain the case of the man whose DHT reportedly spiked and who became hypersexual?

A few honest possibilities, none of which I can fully resolve:

It's likely genuine. That case was documented in Thailand, where Butea superba is native and traditionally harvested. Someone sourcing directly in-country, from people who've harvested this specific tuber for generations, is far more likely to have the real deal than a product that's been through multiple layers of export, processing, and rebranding before it reaches a bottle on Amazon or iHerb.

It could be misattributed. If that case involved a multi-ingredient product rather than isolated Butea, the effect could belong to another ingredient in the formulation. This happens constantly with traditional herbal products, which are frequently sold as blends rather than single-herb extracts.

The proposed mechanism might not even be DHT-related. Some researchers have proposed that genuine Butea superba’s primary activity is cAMP phosphodiesterase inhibition → the same enzyme family targeted by drugs like Cialis and Viagra. That’s a vasodilatory, erectile-function mechanism, not an androgen one. That said, it doesn’t fully explains a hypersexuality presentation. PDE5 inhibitors are well-documented to improve erectile function without producing that kind of drive or behavioral shift. If the case report genuinely showed hypersexual behavior, not just improved function, that argues for something more androgen- or dopamine-adjacent being involved, even if we can’t currently prove it.

The honest conclusion: we may never fully resolve this, because nobody outside Thailand, sourcing directly, with verified identity, seems able to confirm they’ve ever actually used the real herb.

What Actually Raises DHT (Correction + Practical Application)

I need to walk something back first. In my previous DHT article, I listed Butea superba as one of the best DHT-boosting supplements available, based on the same case report discussed above. Given everything covered here, I’m updating that position: I no longer recommend it as a reliable DHT booster, and I’d treat any product on the market claiming to be genuine Butea superba with real skepticism until it comes with actual species-identity testing, not just contaminant screening.

If DHT support is your actual goal, forget the herb aisle for a minute. Here’s the real hierarchy of what moves this needle, ranked by how much confidence I have in the mechanism and the evidence behind it.

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Your average fitness influencer wants you counting macros and nothing else, because protein and calories are the only two numbers simple enough to sell in a 30-second video. Your carnivore guy wants you to trust “nose to tail” and stop overthinking it, as if evolution optimized ribeye for your exact zinc requirement. Your holistic wellness account wants you eating “intuitively,” which is a nice way of saying nobody’s checked a lab value in years. And your biohacker corner of the internet wants you logging every gram into an app, convinced that if the decimal point is precise enough, the deficiency will show up before it becomes a problem.

I’ve been the last guy. For years, I tracked everything in Cronometer (every meal, every gram, every micronutrient percentage) treating the dashboard like it was a lab report. And I’ll say this upfront: it’s one of the only habits from that era I’d tell you to keep. Most people have never once seen a real number next to their zinc or choline intake. They’re not deficient because they’re unlucky. They’re deficient because nobody in their life has ever shown them the number, and you cannot fix a bottleneck you’ve never measured.

Most people under-consume zinc by 30% and then wonder why they get low testosterone at 40. It’s not a myth!

But here’s what almost nobody selling you on “just track it” is talking about: the number on your screen and the number your body actually absorbed are not the same number. Not close. And the gap between them is wide enough that I eventually stopped trying to hit targets in an app and started eating in a way that made the app almost irrelevant, which is exactly where this article is going to end up.

Before we get there, you need to understand why that gap exists in the first place. There are five separate reasons the intake number lies to you, and every single one of them operates whether or not you’ve ever opened the app.

Layer 1: The Database Is an Average, Not Your Food

Open Cronometer, log a cup of spinach, and it hands you a precise number for calcium, iron, magnesium, and folate. That number came from the USDA database, and the USDA database is an average of samples collected from different farms, different seasons, different years, sometimes decades apart.

Here’s the problem nobody mentions when they show you that screenshot. Soil mineral content varies enormously by region, and decades of intensive farming have measurably depleted the mineral density of the same crops grown in the same places compared to fifty years ago. A tomato grown in mineral rich volcanic soil is not nutritionally identical to a tomato grown in soil that’s been stripped by monoculture for three generations, but Cronometer has one number for “tomato.”

Ripeness at harvest matters. Time between harvest and your plate matters, since many vitamins degrade with storage and light exposure. Cultivar matters, since different varieties of the same vegetable can carry meaningfully different nutrient profiles. None of that survives the trip into a single database entry.

A good example is Brazil nuts. Brazil nuts are the richest natural selenium source, but the selenium content varies by more than 100‑fold depending on the region and even the specific tree. In some regions, one nut barely covers 10% of the RDA, while in others a single nut can exceed the daily requirement several times over.

Animal foods carry the same problem, just less discussed, and it traces back to the same root cause as the plants themselves. An animal is only as nutrient dense as what it ate, so a cow grazing on nutrient-dense pasture passes that density up the food chain, while a grain-fed animal raised on depleted monocrop soil is often starting from a nutritional disadvantage before you ever get to the cut.

Even the same animal shifts seasonally depending on what it grazed that month. On top of that, raw versus cooked matters more than people give it credit for, since cooking changes the weight of the food through water loss, which shifts both the nutrient values and the calorie count per gram logged. If you're eating liver, log it as liver, the density difference between organ meat and muscle meat is large enough that it needs its own accurate entry, not folded into a generic "beef" line.

None of this means the app is useless. It means the number you’re looking at is a population average wearing the costume of a precise measurement, and the actual plate in front of you might diverge from that average by a wide margin in either direction.

Layer 2: Antinutrients Intercept Before Absorption Even Starts

Let’s say the database number is accurate for the food in front of you. You still haven’t accounted for what’s sitting in the same bite, actively fighting your gut for that mineral before it ever gets a chance to absorb.

Phytates, found heavily in grains, legumes, nuts, and seeds, bind to zinc, iron, and calcium in the digestive tract and drag a chunk of it out with your stool instead of into your bloodstream. Cronometer will happily tell you a serving of oats contains a respectable amount of magnesium. It will never tell you the phytic acid in that same bowl is actively working against you absorbing it.

Oysters are a prime example. The best source of zinc on the planet. When oysters are eaten alone, zinc absorption is close to 100%. Eat them with black beans and absorption is cut by roughly half. Eat them with corn tortillas, high in phytic acid and zinc absorption from the oysters drops to virtually zero.

Oxalates, concentrated in foods like spinach and almonds, bind calcium in a similar way, and at high enough intake are one of the more well established dietary contributors to kidney stone risk in susceptible people. You’re only absorbing 5% of the total amount of calcium from spinach!

Tannins, present in tea, coffee, and some legumes, bind iron (only non-heme) and can meaningfully blunt absorption if consumed too close to an iron rich meal.

The pattern across all three is identical. The mineral content of the food is real. The antinutrient sitting directly next to it in the same forkful is invisible to the app, and it’s actively working against the number you just logged.

Check out my article on maximizing nutrient density here.

Layer 3: Digestive Capacity, or Can You Even Extract What’s There

Assume the food is dense and the antinutrient load is low. You still haven’t accounted for whether your own digestive system is capable of extracting what’s actually present, because absorption isn’t automatic. It’s a mechanical process, and that process can be broken in several independent ways.

Minerals need to be ionized before they can be absorbed, and that ionization largely depends on adequate stomach acid. Someone with low stomach acid can eat a mineral dense meal and simply fail to extract much of it, because the mineral never gets converted into an absorbable form in the first place. The food was fine. The stomach wasn’t.

Fat soluble vitamins, A, D, E, and K, depend on adequate bile and lipase to be absorbed at all. Someone with sluggish bile flow or low pancreatic enzyme output can eat a diet rich in these vitamins and still run a deficiency, because the vehicle required to absorb them is the part that’s broken, not the diet.

Intestinal inflammation is another layer entirely. Chronic inflammation can blunt the villi lining the gut, the tiny finger like projections that make up your actual absorptive surface area. Blunted villi mean less surface area, and less surface area means lower absorption across the board, regardless of what’s on the plate.

On top of all of that, some people are simply poor absorbers of specific nutrients for reasons that have nothing to do with any of the above, which is a large part of why I built a pattern based framework in the first place rather than a single blanket protocol.

And then there’s the tenant you didn’t invite to dinner. Your gut bacteria are not passive bystanders while food passes through. Certain species actively compete for and consume specific nutrients before your body gets first access, tryptophan being one well-documented example. You can eat a tryptophan-rich meal and still run low, not because the food lacked it, but because something living in your gut got to it first.

Layer 4: Your Body Actively Regulates What It Lets In

This is the layer that changed how I think about tracking entirely, and it’s the one I opened this article with. Your gut is not a passive pipe that lets through a fixed percentage of whatever you eat. It’s a regulated system, constantly adjusting how much of a given nutrient it lets in based on your current status. The same food, eaten by the same person, gets absorbed at wildly different rates depending on what your body already has on hand.

Copper is a sharp example of nutrient‑dependent absorption. Human studies show that when dietary copper is very low (under about 1 mg/day), the intestine can absorb roughly 50–75% of what you eat. Push intake up into the several‑milligram range and fractional absorption drops to under 20%, sometimes near 12%, with the liver simultaneously ramping up biliary excretion.

In other words, the same gut lining behaves like a high‑efficiency copper sponge when you’re marginal and like a gatekeeper when you’re replete. Cronometer has no idea where you are on that spectrum. It only reports the copper content of your food; it does not account for your current copper status or how much of that copper you’ll actually absorb and retain

Iron works through a similar but distinct mechanism, governed largely by a hormone called hepcidin. When your iron stores are replete, hepcidin rises and shuts down absorption almost entirely, regardless of how much iron rich food you eat. Inflammation independently raises hepcidin as well, which is part of why iron deficiency and inflammation can coexist and make each other worse. The dietary iron number in the app means almost nothing without knowing what hepcidin is doing that day.

Zinc follows a comparable logic through a protein called metallothionein. Chronic high zinc intake induces more metallothionein in the gut lining, which binds zinc and reduces how much makes it past the enterocyte into circulation. Zinc and copper also compete for overlapping absorption pathways, which is exactly why the ratio between the two matters as much as either number alone, something I’ll come back to later in this article.

Calcium absorption relies heavily on vitamin D‑dependent active transport. At low vitamin D and calcium intakes, the intestine up‑regulates this active pathway to pull more calcium out of whatever food is available. As intake rises, passive diffusion through the gut wall contributes more and fractional absorption actually falls, even though total absorbed calcium is higher. When dietary calcium still falls short despite these adjustments, the body has a fallback your tracking app will never show you: parathyroid hormone (PTH) rises and starts mobilizing calcium from bone to keep serum levels stable, protecting the blood at the direct expense of the skeleton.

Chronically elevated PTH is linked with bone loss, kidney stones, cardiovascular risk, and inflammatory burden across multiple tissues. Your nutrient app can tell you that your calcium intake looked adequate on paper, but it has no way of telling you that your parathyroid hormone spent the afternoon quietly borrowing from your skeleton to make up the difference.

Magnesium follows a looser version of the same pattern, some evidence suggests fractional absorption rises somewhat at lower intakes, though the regulation here is far less tightly characterized than the other three, and I’d call it the weakest example on this list rather than overstate it.

The throughline across all four is the same. Cronometer reports intake as though it equals delivery. It cannot, because the number that actually matters isn’t what you ate. It’s what your body, in its current state, decided to let through the door.

Layer 5: Genetics Can Shift the Target Itself

Every layer above assumes the target you’re aiming for, the RDA or DRI value Cronometer compares you against, is the right target for you specifically. It often isn’t, because those values are population medians, and your genetics can move your personal requirement well outside that median in either direction.

The MTHFR mutation is probably the most talked about example, and it shifts riboflavin (B2) requirement upward as part of how the enzyme it affects functions. Poor biotin recycling is another, where certain people simply cycle through and lose biotin faster than a standard intake target accounts for.

My own experience running whole genome sequencing turned up a variant affecting carnitine handling that lines up with a lifelong pattern of small muscle fatigue I’d noticed for years without ever having a mechanism for it. Cronometer would have told me my carnitine adjacent nutrient intake looked fine. While my genetics were asking for more all along.

This is the layer that finally closes the loop on why intake tracking alone was never going to get me, or you, all the way there. Even a flawless log, eating foods with accurate database values, zero antinutrients, perfect digestion, and no adverse absorption regulation working against you, can still land you short if your personal requirement was never the population average to begin with.

So if tracking intake can’t actually tell you what’s happening inside your body, what does?

The Implementation Protocol

Everything above is the diagnosis. This is what I actually did about it, and what I’d tell you to do if you want to stop chasing a number that was never going to give you the full picture.

Let’s get into it.

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The carnivore crowd tells you saturated fat is testosterone superfood → eat a pound of tallow and thank your ancestors.

The heart-health establishment tells you saturated fat is a slow-motion heart attack, so switch to canola.

The seed-oil-is-poison crowd says the exact opposite, and the gut health influencers split the difference and just tell you all fat is “inflammatory” if you’re sensitive.

Four camps, four confident answers, and somehow all four cannot be true at the same time.

I’m not here to argue theory. I’m running the panels.

This didn’t come from a textbook. It came from years of watching myself and clients react completely differently to fats that get filed under the exact same “saturated fat” label, dairy tolerated, tallow not, lamb somewhere in between. Enough pattern to notice, not enough to prove (via tests).

This isn’t new thinking, even if it feels that way. Weston Price spent the 1930s travelling to isolated populations around the world and found something nutrition science has spent decades trying to unlearn: it was never “fat” that determined a population’s health; it was which fat, from which animal, prepared which way, alongside which foods. Butter-fed villages looked nothing like tallow-fed ones. He photographed the difference in people’s faces before anyone had a word for microbiome.

Here’s the part that surprised me personally. I used to assume red meat itself was the problem when I felt inflamed after dinner. Turns out the meat was rarely the issue. The rib eye with full marbling, fried in tallow and stacked next to a pile of potatoes was doing something completely different in my gut than the same cut of lean beef eaten with honey at breakfast. Same animal. Same protein. Two entirely different biological events. That’s the twist this whole article is built around, and once you see it, you can’t unsee it in your own reactions.

The purpose of this article is to make you aware of how fat in different amounts, from different sources and in different combinations, affects you and how it can contribute to indigestion and gut inflammation.

So we start with bile.

Bile Isn’t a Detergent. It’s a Courier Who Can Be Bribed.

Here’s why you should care before you care how it works: the reason a fatty meal can leave one person clear-headed and another person foggy, bloated, and inflamed for two days has almost nothing to do with how much fat they ate. It has to do with who’s waiting for that fat once it hits their gut.

But first, let’s actually explain what bile even is, because most people have heard the word their whole life and couldn’t tell you a single real thing about it.

Bile is a fluid your liver makes constantly, drop by drop, all day, whether you’re eating or not. Think of your liver as a factory that never turns off the assembly line. That fluid doesn’t get used right away. It gets pumped into a small pouch tucked underneath your liver called the gallbladder, which acts like a storage tank, concentrating the bile and holding it until it’s needed.

Here’s the trigger. The moment fat shows up in your small intestine, specialized cells lining your gut release a hormone called CCK (cholecystokinin, but nobody needs to remember that name). CCK is basically a text message sent straight to the gallbladder that says “fat just arrived, send the tank.” The gallbladder squeezes, and bile gets released through a duct straight into the intestine, right where the fat is sitting.

Now here’s the actual job bile does. Fat and water don’t mix. Ever tried mixing oil and water in a glass? It separates into layers no matter how hard you shake it. Bile is what breaks that fat into tiny droplets small enough for your body’s fat-digesting enzyme, lipase, to actually get at it and break it apart. Without bile, fat just sits there in big greasy clumps that nothing can touch. This is the “detergent” job most people have heard about, the one where bile breaks grease into small manageable pieces, the same way dish soap breaks grease off a pan.

But here’s the part almost nobody was ever taught, and it’s the whole reason this article exists. Bile doesn’t do its job and disappear. Roughly 95% of it gets reabsorbed further down your gut and shipped back to the liver to be reused, over and over, for years. Before that happens, though, it has to travel through a stretch of intestine crawling with bacteria, and some of those bacteria have learned to intercept it on the way through.

Picture bile leaving the liver as a clean, sealed courier package. That’s called a “primary” bile acid, doing exactly the job it was designed for. Certain bacteria, Clostridium scindens being the main one to know, have figured out how to open that package mid-transit, strip pieces off it, and reshape it into something different, called a “secondary” bile acid, things like deoxycholic acid. These reshaped versions are the ones tied to barrier damage and inflammation in the gut lining.

One nuance worth adding here, because it's easy to walk away thinking "secondary bile acid" just means "bad." It doesn't. Secondary bile acids aren't villains by default, some of them are actually part of a healthy, functioning gut, supporting immune tolerance and helping maintain the gut barrier when a healthy microbiome is producing them in the right amounts (e.g. UDCA, iso-LCA, etc). The problem is specific to certain hydrophobic, unconjugated forms, deoxycholic acid and lithocholic acid being the two worth knowing, and only when they build up in excess. Those particular versions are the ones shown to damage the intestinal lining, drive oxidative stress, and raise cancer risk over time. So it's not "primary good, secondary bad." It's "the right secondary bile acids, in the right amount, from the right bacteria, are fine. The wrong ones, piling up because the wrong bacteria are in charge, are the problem."

So the honest answer to “does fat cause inflammation” is: it depends who’s working the docks that day. A clean, well-regulated gut has the right bacteria in the right amounts, recycles bile efficiently, and nothing bad happens. A dysbiotic gut, meaning the bacterial balance is already off, lets the wrong bacteria intercept that courier on every single meal, and now you’ve got a steady drip of inflammatory secondary bile acids showing up uninvited, day after day, meal after meal.

Fat isn’t the villain. It’s just the delivery truck. The question is who’s waiting at the loading dock.

Fat doesn't cause inflammation on its own, your bacteria decide that. Bile gets released to digest fat and mostly gets recycled back to the liver, but on the way through, certain bacteria (like Clostridium scindens) can convert it into inflammatory "secondary" bile acids. A clean gut recycles bile without issue; a dysbiotic gut turns that same bile into a steady drip of gut irritation every meal.

The Truck That Never Gets Unloaded

Here’s why you should care before you care how it works: someone can be eating genuinely clean fat, olive oil, dairy fat, the good stuff, and still get floating stool, bloating, cramping, and slow-building nutrient deficiencies.

Bile’s job, remember, is emulsifying fat, breaking it into small enough droplets that something else can finish the job. That something else is lipase, an enzyme made by the pancreas, and its job is to actually cut those fat droplets down into pieces small enough for your gut wall to absorb. Bile packs the fat into small crates. Lipase is the foreman who’s supposed to show up and unload each crate.

When lipase output is low, from a stressed pancreas, chronic inflammation, or reduced enzyme output over time, the crates never get unloaded. They just keep moving down the truck route, further and further into parts of the intestine that were never built to handle raw, unprocessed fat.

Clinically, this looks like steatorrhea: fatty, bulky, foul-smelling stool that floats and doesn’t clear well, along with bloating, cramping, and over time, deficiencies in fat-soluble vitamins (A, D, E, K) and essential fatty acids, because none of that got absorbed either. If you’ve ever had genuinely oily, hard-to-flush stool after a meal that wasn’t even that fatty, that’s the picture.

Here’s what’s bad: fat malabsorption stresses the gut, feeds dysbiosis, and drives barrier dysfunction, through a few separate routes. Undigested fat and bile-fat mixtures moving into the colon act as a mechanical and chemical irritant to the gut lining, and can raise inflammatory markers like secretory IgA and calprotectin along the way. That excess fat sitting in the gut also changes what bacteria thrive there, favoring bile-tolerant, pro-inflammatory species and increasing exposure to LPS, the same endotoxin that’s been showing up throughout this whole series. And chronic fat malabsorption, the kind seen in conditions like exocrine pancreatic insufficiency or IBD, tends to travel alongside damaged villi and genuinely impaired barrier function, not as a coincidence, but because the same environment that causes one tends to cause the other.

There’s a systemic version of this story too, worth a quick mention even though it’s a different mechanism. When enzymes that clear fat from the bloodstream, like lipoprotein lipase (LPL), are impaired, triglyceride-rich particles and cholesterol accumulate in the blood, liver, and other organs, driving its own separate inflammatory and metabolic damage. Different location, same theme: fat that doesn’t get properly processed or cleared, whether in the gut or in circulation, tends to leave inflammation in its wake.

Unabsorbed fat doesn’t have to be a poison to be a problem. It just has to sit there long enough for the wrong bacteria to notice.

Chain Length: The Highway vs. The Toll Road With Fourteen Checkpoints

Picture two versions of the same package trying to get across town. One takes the highway, straight through, no stops. The other has to clear customs, get searched, get re-packaged, and pass through fourteen checkpoints before it arrives.

That’s the difference between medium-chain fat and long-chain fat, and it’s a bigger deal than most people realize, because “saturated fat” gets treated as one lane when it’s actually two completely different roads.

Coconut oil is dominated by lauric and myristic acid, both medium-chain. These get absorbed almost directly into the portal vein, mostly skipping the whole bile-and-lipase production line. Less bile released, less raw material sitting around for bacteria to convert into secondary bile acids, less opportunity for anything to go wrong.

Tallow, lard, and fatty red meat are dominated by long-chain fats, palmitic and stearic acid mostly, and these need the full system running: full emulsification, full lipase activity, full bile cycling.

If bile flow is sluggish or the gut is already dysbiotic, this is exactly the fat profile most likely to cause trouble, and it’s not a coincidence that research keeps flagging palmitic specifically, while lauric and myristic acid come back with far more mixed, sometimes even favorable, results.

Same box labeled “saturated fat.” Two completely different roads to get there.

Chain length decides how much of the machine turns on. Saturation alone never told you that.

P.S. Here's the twist behind why palmitic acid (the main fat in animal fat) keeps getting flagged in study after study. In people who are obese or insulin resistant, the liver is constantly converting excess glucose into palmitic acid through a process called de novo lipogenesis, basically manufacturing its own palmitic acid from sugar, whether or not any was eaten. So a lot of the palmitic acid showing up in these people's blood was never on their plate. It was made in-house from carbs. That means the association studies blaming dietary palmitic acid may actually be picking up the fat someone's own liver is manufacturing from a high-sugar, insulin-resistant state, not the steak they ate. The palmitic acid coming from food isn't the one causing the damage those studies keep finding.

Saturation alone doesn't tell you how hard a fat is to digest, chain length does. Medium-chain fats (coconut oil) mostly skip the bile system; long-chain fats (tallow, red meat) demand the whole process, which is harder on an inflamed gut. And a lot of the palmitic acid blamed in studies isn't from food at all, it's made in-house by the liver from excess sugar in insulin resistant people.

The Food Matrix: Who’s Getting Fed at the Underground Buffet

Two fats can be equally saturated, equally long-chain, and still behave like strangers in your gut, because fat never travels alone. It brings roommates.

Red meat’s fat arrives with heme iron and sulfur-rich amino acids like taurine and cysteine riding shotgun. Those sulfur groups get bolted onto bile acids on the way out, and there is a specific organism, called Bilophila wadsworthia, that shows up to a very specific buffet: taurine-conjugated bile acids from red meat. It eats, it multiplies, and its metabolic waste product is hydrogen sulfide, a compound with a well-documented habit of inflaming the colon.

Dairy fat doesn’t set that table. Milk is essentially iron-free and carries far less of those sulfur amino acids relative to muscle meat. Same saturation category on paper. Nothing close to the same buffet for Bilophila underneath.

This is the actual explanation behind something I see over and over in clients: people tolerate dairy fat better than beef fat, and often tolerate lamb better than beef too. It was never really the fat. It’s who that fat is feeding downstairs while you’re just eating dinner.

Even mouse studies back this up directly. Compare fat sources rather than isolated fatty acids and the source itself, not just the saturation number, drives the biggest microbiome shift. Lard wrecked the gut community significantly harder than canola oil, same fat content, different guest list. Butter, tallow, lard, olive oil, and coconut oil are not the same experiment just because a spreadsheet groups a few of them under “saturated.”

Before the carnivore crowd starts sharpening pitchforks: most people handle saturated fat, including red meat fat, completely fine. This isn't an argument that red meat is dangerous. It's that tolerance is a dial, not a switch, and how much you eat, what you eat it with, and even what time of day you eat it all move that dial. A dysbiotic gut with a Bilophila problem reacts badly to a fatty ribeye and rice at 8pm. That same gut, or a healthier one, might handle lean beef and honey at breakfast without a hint of trouble.

The gut doesn’t read nutrition labels. It reads who showed up with the fat.

The Combination Multiplier

Here’s a scene almost everyone recognizes but nobody’s diagnosed correctly. Steak and potatoes at 8pm. Butter on both. You wake up at 3am with your gut lit up like a building on fire, and by morning it’s still complaining about the smoke.

You blame the steak. You cut red meat. Symptoms barely move.

The steak was rarely the actual problem. Fat slows gastric emptying on its own. Starch behind that slowed emptying, especially with the enzyme output that inflammation itself tends to suppress, becomes fermentable material sitting in a traffic jam. Stack a high fat load on top of a high starch load in a gut that’s already struggling to process either, and you get food sitting longer, fermenting harder, producing more gas, more pressure, and more endotoxin than either macronutrient would cause on its own.

This is also why “just go low fat” or “just go low carb” isn’t the oversimplified advice it sounds like. It’s not that fat or carbs are individually dangerous. It’s that the overlap, in a gut that can’t fully handle both, is the collision. Remove one side of the overlap and the collision stops happening.

Same red meat that wrecks you at dinner next to rice can sit completely fine at breakfast next to honey. The protein never changed. The traffic pattern around it did.

If someone says “I can’t handle steak and potatoes,” ask them which half they’ve actually tested alone. Almost nobody has.

The Redemption: Fat Was Never the Enemy

None of this means fat, even saturated fat, deserves permanent exile. Several fat sources are quietly doing repair work, and that gets lost every time “avoid saturated fat” gets repeated as a blanket rule.

Dairy fat carries odd- and branched-chain fatty acids, C15:0 and C17:0, manufactured by bacteria in a cow’s rumen before they ever reach the milk. Research keeps tying these to lower inflammatory markers and even protective effects in infant gut studies. Goat and sheep milk push this further still. A larger share of their fat is short-chain, and sheep milk in particular runs high in butyric acid, the exact fuel your colon cells prefer to eat.

There’s a second layer inside milk that has nothing to do with the fatty acids themselves. Calcium in milk binds with fatty acids and bile acids to form calcium soaps, which pulls free, reactive bile acid out of circulation in the colon. A built-in buffering system riding inside a food most people think of as “just a drink.”

Egg yolk gets filed in the same suspicious drawer as red meat fat, but it’s actually one of the richest sources of phosphatidylcholine, a phospholipid your liver and gut both use as raw material for membrane repair and healthy bile composition. It’s not fat sitting there being fat. It’s a supply truck.

And well-prepared red meat deserves its name back too. The problem was never “red meat.” It was iron, sulfur, high fat, and starch all arriving at once to a gut that was already inflamed. Lean cuts, pressure-cooked until the connective tissue gives up, eaten with fruit or honey instead of rice, ask almost nothing of an already-struggling bile system. Someone with genuinely compromised digestion can usually handle this version of red meat long before they can handle the fattier, starch-paired version.

The category was never the villain. The version of the category you chose was.

The Actual 6-Step Protocol: What To Do With All of This

If you already know fat is a problem for you but don’t know which of these six levers is actually yours, that’s exactly what a personalized health report solves. It maps your specific pattern (bile flow, enzyme output, matrix sensitivity, combination triggers) against everything in this framework and tells you which step to start on, not which step sounds right in an article. Get your health report here.

If you just have a specific question right now (what to eat tonight, whether your stool is telling you “more bile” or “less bile,” which fat source to try first) Ask Hans is trained on this entire framework and gives you a direct answer in under a minute. No guessing which step applies to you.

Understanding the mechanism is one thing. Knowing what to actually change on your plate tomorrow is another. Here’s the step-by-step version, in the order to run it.

Step 1: Turn the volume down before you diagnose anything. If fat is currently a problem, the fastest lever isn’t finding the “perfect” fat, it’s just reducing total fat intake for a short window. Drop to around 30-40g of fat a day. Less bile released, less substrate for the wrong bacteria to convert, less demand on a system that’s already behind. This isn’t a permanent fix. It’s turning the fire alarm off so you can actually hear what’s going on. It’s easy to do if you just go very lean on all foods. 1% milk. Top sirloin. >95% ground beef. Organ meat. Chicken/turkey breast or lean fish or shellfish. Those as the main protein sources.

The order you run these six steps in matters more than which one you start with, and most people run them backwards. Below I discuss the rest of the steps.

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I spent years on the supplement side of that confusion. Ran every protocol. Tested every stack. Worked with thousands of people who had done the same. And the pattern that kept emerging was not which compounds worked best. It was that the people who made the most progress were the ones who had their food so dialled in that supplements became optional. Not irrelevant, but optional. There is a difference.

This is the system I built from that realisation. It is not a meal plan. It is not a diet identity. It is a framework for matching food to your current digestive state, building a foundation strong enough to generate real signal, and only then adding anything on top. I call it Tier 1. The rule is simple: nothing gets layered on until this is solid.

Most of what people think they need from a bottle is a food problem wearing a deficiency costume. This guide is how you find out.

One caveat before anything else: Tier 1 is not a promise that food alone fixes everything for everyone. Some people genuinely need targeted support on top of a clean dietary base → a thyroid that needs assistance, a gut too damaged to recover on food alone, an enzyme deficit that diet cannot fully compensate for. That is real and we will address it. But you cannot know what you actually need until you know what food alone can do. And most people have never found out.

Find Your Starting Point

Before reading further, answer these three questions. Your answers tell you which template to start with. Once you know your template, the rest of the article speaks directly to you.

Question 1: What do your mornings look like?

A → I wake up cold, with little to no appetite. Coffee before food is the only way I function. My hands are cold until mid-morning or later.

B → I can eat in the morning but keep it light. A heavy breakfast sits badly. Some days appetite is fine, some days it isn’t.

C → I wake up hungry and can eat a full meal without issue. Energy is generally stable through the morning.

Question 2: What does your digestion tell you?

A → My stool regularly floats, or I need more than two or three wipes, or I spend more than five minutes on the toilet. Bloating, gas, or a heavy feeling after meals is common.

B → Digestion is inconsistent. Some meals clear well, others sit badly. I have not identified a clear pattern yet.

C → Digestion is generally good. Stool sinks, clears quickly, wipe count is low. I rarely feel heavy or bloated after eating.

Question 3: How do you feel in the hour after eating?

A → I often feel foggy, heavy, or worse after meals than before. Energy tends to drop rather than hold steady.

B → It depends on what I eat. Some meals give me energy, others crash me. I have not fully mapped the pattern.

C → Meals generally give me energy. I feel stable and functional for three to four hours after eating without needing caffeine or snacks.

Your result:

Mostly A answers: start with Template 1. Your digestion is compromised and morning demand is low. The milk protocol is your entry point.

Mostly B answers: start with Template 2. Moderate digestion that responds well to structure. The TestoShake plus one solid meal is your starting point.

Mostly C answers: start with Template 3. Functional digestion that is ready for a full food-first approach.

Mixed answers: default to Template 1 for two weeks, then reassess. It is always better to underestimate digestive capacity and build up than to overestimate it and create setbacks.

Your Body Has Been Talking. You Just Haven’t Learned the Language Yet.

Before we get into what to eat, you need a way to know whether what you’re eating is actually working. Most people don’t have one. They feel vaguely okay, vaguely off, and have no idea which meal caused which outcome.

The standard is simple. A healthy bowel movement sinks, passes in under five minutes, and leaves nothing behind on the toilet paper. One wipe and done. That is what’s known as the ghost wipe, and it is the single most honest piece of daily feedback your gut gives you. If you are spending ten minutes on the toilet, wiping five times, and the stool is floating, your gut is telling you something is wrong.

Beyond the bathroom, your body is giving you signals you’ve probably learned to normalise. Blurry vision after eating is intestinal inflammation showing up in your blood. Dandruff that flares after certain meals is the same process expressing through the scalp. Nasal congestion that appears in the evening after a big dinner is not a coincidence. Skin breakouts, joint stiffness, brain fog that arrives like a curtain dropping an hour after lunch, restlessness that makes sleep feel shallow and unearned. These are all the same fire, just different rooms of the building.

The symptom checklist to keep in your head: floaters in the toilet, wipe count above two, blurry vision after eating, post-meal energy crash, bloating or a heavy feeling that sits for hours, skin flares or dandruff, nasal congestion, a blood sugar rollercoaster feeling of high then crash then crave, cold hands and feet, restlessness. Any of these appearing consistently after eating means something in the current diet is creating inflammatory load your gut cannot neutralise fast enough.

Here is the reframe that changes everything: if a food produces none of those signals, it is fine for you right now. It does not matter what mainstream nutrition says about it. You are not a population study. You are one person with one specific gut in one specific state. The feedback loop is the test.

I used to get blurry vision and dandruff from eating jelly. Actual jelly. After fixing my gut, I can eat beans, hot salsa, and chilli with zero issues. Energy good, vision clear, no dandruff, no acne. The foods did not change. My gut did. Food sensitivities are not a life sentence. They are a signal that the gut is not ready yet. The goal of Tier 1 is to build a gut that eventually handles everything, not to spend your life on a permanent restriction list.

The flip side is equally important. If a food is currently producing any of those signals, avoid it while you build the foundation. Not forever. Just now.

Starches/carbs Do Not Make You Fat or Diabetic. Combination Does.

This needs to be said clearly before anything else, because the fear of carbohydrates is so embedded that most people read a protocol built around potatoes and milk and immediately wonder if they’re being set up to gain weight.

They’re not. And the evidence is worth understanding.

The potato diet, literally just potatoes, with a small amount of olive or coconut oil if fat is desired, causes rapid weight loss in virtually everyone who tries it. Not because of any magic compound in potatoes. Because potatoes eaten on their own are almost impossible to overeat. The palatability drops without added fat, and appetite self-regulates naturally. Add butter, cream, cheese, and make the meal complex and delicious, and suddenly you are consuming twice the calories without noticing. That is not a carbohydrate problem. That is a palatability and fat combination problem.

Walter Kempner made this point more dramatically in the 1940s at Duke University. His rice diet used white rice, fruit, juice, and table sugar, near-zero fat, near-zero protein, almost entirely carbohydrate, to reverse type 2 diabetes, shrink enlarged hearts, and repair kidneys that were already failing. The diet was effective enough that it attracted patients from around the world. It was also so unpalatable that Kempner eventually had to keep patients at his institute to enforce compliance. Some accounts are colourful. The results were not in dispute. Starch alone, in the absence of excess fat, does not cause metabolic disease. The combination of high carbohydrate and high fat, eaten together, in a state of chronic inflammation and sedentary living, does.

The practical implication: starch eaten on its own digests fastest, leaves the least residue, and carries the lowest risk of causing problems. A meal of potatoes with nothing added clears quickly and cleanly. A meal of potatoes drowned in butter, topped with sour cream, and served alongside a fatty protein takes far longer to process and introduces multiple variables that can cause bile flow issues, slow transit, and intestinal inflammation. Both meals contain starch. Only one is a problem.

Starch alone is less satiating (same as fruit). That is the trade-off. If you need to hold blood sugar stable for four or five hours, a starch-only meal will not always get you there. A combination meal with protein and a modest amount of natural fat will. Both are tools. Matching the tool to the moment is the skill.

The One Rule That Governs All of This

Every meal follows one structure: one protein source and one carb source.

That is it. Not a superfood stack. Not a macro calculation. One protein, one carb, and the meal is complete. The reason this works is not mystical. Fewer ingredients mean fewer variables. When something goes wrong, you can identify it. When something works well, you know what to repeat. A meal with twelve ingredients is a meal you can learn nothing from.

The rule applies differently depending on your digestive state, which is where most people go wrong. A functional gut can handle steak and potatoes cleanly. A compromised gut often cannot, and not because of the steak or the potatoes individually, but because the protein and complex carbohydrate compete for digestive resources that the gut cannot fully supply right now. The starch can end up fermenting around undigested protein, and what should have been lunch becomes a gas-producing, inflammation-generating event that you feel through the following morning.

The solution for a compromised gut is not to avoid starch. It is to change the protein pairing. Dairy and eggs digest far more cleanly than red meat when the system is struggling. Potatoes with eggs, rice with milk, fruit with yogurt → these combinations clear without drama. They are less impressive on paper and significantly more effective in practice.

When digestion is functional, the full range opens. Red meat with any Tier 1 carb works well. The key variable controlling whether meat and starch work together is not the starch type, it is the fat load. Lean to medium-lean meat paired with an easy-to-digest carbohydrate like fruit, fruit juice, or honey is a valid meal at any time of day, including breakfast. The moment fat climbs significantly, bile flow becomes the limiting factor. A lot of people have bile issues they don’t know about, liver congestion, sluggish gallbladder, poor bile acid recycling. When fat hits a compromised bile system, those bile acids become inflammatory rather than digestive, transit time slows, and the intestinal lining takes damage. This is why low-fat protein sources with easy carbs are the starting point, not a permanent restriction.

One category worth elevating here: organ meats. Most people think of liver, kidney, gizzards, and beef tongue as intense foods that require a strong stomach. The opposite is often true. These are softer meats with less connective tissue and collagen matrix than muscle cuts like sirloin or chuck. Pressure-cooked gizzards in particular are extraordinarily easy to digest → lean, rich in collagen (which directly supports gut lining repair), and so soft they require almost no mechanical breakdown. They are one of the better breakfast proteins for someone with a compromised gut who still wants genuine nutrient density rather than eggs for the fourth consecutive day.

Pressure cooking is the single most impactful preparation change you can make for any protein. Collagenous cuts like oxtail, shin, shank, and gizzards become genuinely easy to digest after pressure cooking; the connective tissue breaks down, the muscle fibres soften, and the digestive demand drops substantially. The one consideration with fattier collagenous cuts is that the fat content is higher. Gizzards avoid this entirely → they are lean, collagen-rich, and become very soft under pressure, making them one of the cleanest options for mornings when digestion is not fully active.

Where Sourdough and Refined Carbs Actually Fit

Sourdough is a refined grain product. The nutrient density is low. People eat it because it tastes good, and that is an honest and legitimate reason to eat something, but it should not be confused with nutritional strategy.

The question is not whether sourdough is good or bad. The question is what the rest of the diet looks like. If you are hitting daily red meat, eggs, milk, liver regularly, and oysters a few times a week, you have a nutritional buffer that is deep enough to absorb some refined carbohydrates without consequence. A slice of sourdough is not displacing anything important when those bases are covered. It is a pleasant addition to a foundation that is already solid.

If those bases are not covered, if the diet is built around convenience foods with occasional healthy additions, then sourdough and sugar are taking up space that should be used for something that actually moves the needle. The nutrient density in the foundation is what buys flexibility in the margins. Earn the foundation first and the flexibility follows naturally.

The broader principle applies to all refined carbohydrates. Sugar, white rice, honey, fruit juice: their role in the diet scales with how nutrient dense the rest of the diet is. A person eating liver twice a week and a kilogram of red meat daily can afford to use honey freely. A person surviving on chicken breast and protein bars cannot.

You now understand the reasoning. One protein, one carb, fat load as the real variable, starch rehabilitated, refined carbs contextualised. That is the foundation most people spend years trying to piece together from conflicting sources.

What follows is the application, and it is more specific than most people expect.

The rest of this article covers the most underused food in Tier 1 and exactly how to use it as a complete meal, why the morning is the hardest problem to solve and the four options ranked by digestive demand, a short diagnostic to identify your exact starting point before you change anything, and three day templates you can run from tomorrow. Most people who implement this properly do not need a single supplement. Some do. The diagnostic tells you which camp you are in.

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