What I’ve learned, or at least inferred from studying α-MSH (alpha melanocyte-stimulating hormone) in more depth, is that it has the potential to act as a braking system in our immune system.

Which I’m going to expand on later in the article, because from a first-principles perspective on immune biology, it actually makes perfect sense

Your biology, and your immune system, essentially has certain processes that act as balancing boards, allowing your body to return to an appropriate level of functioning.(homestasis)

It does this through different arms, pathways and feedback loops that all interplay with each other.

My idea, or at least what I’ve extrapolated from studying, is that α-MSH extends beyond just being a ‘pigmentation hormone/peptide’

It also has an innate role to play in the immune system.

More specifically, it may act like an endogenous brake of sorts.

2. The Immune System Needs a Goldilocks Zone

See, our body likes to operate within a Goldilocks zone.

For example, in order for us to adequately respond to something like an infection, we actually need immune signalling.

We just don’t need too much of it.

Because then we cross over into the domain of OVER-ACTIVATION.

So there’s a balance to be had:

Not enough inflammation / immune signalling → can’t respond adequately to infection.

Too much inflammation / immune signalling → crosses into inflammatory territory.

So the body’s goal isn’t necessarily to have NO immune activity.

It’s about having appropriate activation at the right times

3. Inflammation Isn’t Automatically Bad

I’m going to explain how this actually works, and why we need to be careful that we don’t orient ourselves emotionally to words like “inflammation” or “pro-inflammatory cytokines.”

Because these things, in the right circumstances, can ACTUALLY be good for us.

Pro-inflammatory cytokines, for example, can act as signalling molecules that help recruit and activate immune cells during an infection through processes such as chemotaxis.

If that process didn’t exist you could quite literally struggle to mount an adequate response to an infection.

So I suppose what I’m trying to tell you is that everything must be there, because everything has its role.

The problem isn’t necessarily the existence of inflammation, its the context and magnitude of that inflammation.

And this is where α-MSH becomes MUCH more interesting.

4. α-MSH remember its more Than a “Pigmentation Hormone”

And the reason I’m countering this argument is because based on mainstream thought, it has garnered most of its attention around the idea of being a “pigmentation hormone.” because of the association with peptides such as Melanotan I and ll

But I think that sort of short sells it.

It isn’t simply a one-trick pony, but part of a much longer chain that’s involved in the neuroendocrine–immune regulatory system.

And it all starts with the POMC & melanocortin pathway.

5. The POMC → α-MSH Pathway

POMC = proopiomelanocortin is a precursor protein that enzymatically cleaved into smaller peptide fragments. (By an enzyme called PSCK1/2')

And α-MSH is one of these peptide fragments that is produced by this process.

I also want to be sure to mention that A-MSH It’s not what it is that interests me, by the way.

It’s more what it does, and what it’s connected to.

Because α-MSH can act as a ligand for melanocortin receptors.

In simple terms.

α-MSH = is a signal & melanocortin receptors = are the receptors that receive the signal.

But it gets better.

Would you like to guess where melanocortin receptors exist?

Immune cells.

Which is where the interesting link between the immune system starts.

6. The Melanocortin System and Immune Cells

This is where it all started to come together for me.

Melanocortin receptors aren’t confined to the systems traditionally associated with pigmentation as you would expect.

Different melanocortin receptors are expressed across various immune cells such as

• Neutrophils (Most abundant immune cell in the blood stream)

• T-cells (Produced by the bone marrow, trained by the thymus)

• Monocytes (Which differentiate into macrophages)

• Macrophages

Which raises an almost obvious question:

Why would the immune system have receptors capable of receiving signals from melanocortins?

And that creates a much broader picture beyond pigmentation.

To me it starts to look like it may be part of a regulatory communication system between the nervous, endocrine and immune systems. (an arm of sorts)

7. Then I found KPV.

This is where it all started to get really interesting for me…

I was reading through the studies, and using deductive reasoning to start putting the pieces together.

It actually started when I was looking into the tripeptide KPV, lysine, proline, valine — which is a sequence derived from α-MSH.

Which made me ask a question:

If KPV is a fragment of α-MSH, and KPV itself appears to have anti-inflammatory properties, then where does the biological activity come from?

And why does it retain biological activity associated with the fuller peptide?

That’s one part which really caught my attention.

Because you’re taking a much larger peptide, breaking it down into a smaller fragment, and yet that fragment can still retain the biological activity and information.

So what exactly is being retained?

Where is that information encoded?

And how does a fragment of the whole retain some of the functional characteristics of the whole?

8. The Bohm Connection

It actually reminds me of a quote attributed to David Bohm:

“Everything is a whole with parts, and every part exists as the whole.”

And whether you want to take that purely philosophically, or use it as a way of thinking about biology, I think there’s something interesting here.

Because biology is full of systems within systems.

Parts make up wholes.

Wholes contain parts.

And sometimes, when you isolate a particular part, it can still carry some of the functional properties of the larger system it came from.

And that brought me back to KPV.

Because if KPV is a sequence within α-MSH, and KPV has biological activity of its own, then I started asking:

Is there something about the structure of α-MSH that gives rise to this biological activity, and does KPV retain part of that functionality?

That was the question that sent me further down the rabbit hole…

9. So What Is α-MSH Actually Doing?

This is where I think the distinction becomes important, Im not saying that α-MSH solely exists purely to “suppress inflammation.”

That would be me over simplifying, I think α-MSH appears to participate in regulating your immune activity.

And it helps regulate how strongly it responds and how that response is controlled..

10. Why This Gets Interesting in CIRS / Mold Illness

This is where my interest in α-MSH became much more practical.

I’ve seen the implications of this firsthand when treating clients with CIRS / mold-related illness, where low α-MSH has been discussed in the context of the broader physiological picture.

And it raises an interesting possibility:

If α-MSH participates in regulating immune signalling, then reduced α-MSH signalling could theoretically remove some of that regulatory braking capacity, which is why this would need to be rectified to restore overall immune balance.

I hope you enjoyed reading

Oran/Biohacker.

We’ve all been there, you start something new, forced to suspend your expectations because you have no idea what you’re doing, and you assume your first take will be far from perfect.

But that uncertainty actually gives you an innate sense of power.

At one point, I was the person who believed there was a perfect way to do things. The reality is: the true art, or end result, usually lies in a thousand iterations.

I’ve seen this directly in martial arts and in health.

Today, I’m tying some of these concepts together in a simple form, in hopes you’ll be able to grasp them.

The Iterative Mindset and “Fail Fast”

My core idea or running thoughts are this.

Having an iterative mindset, or using a “fail fast” framework, doesn’t just expose you to more data.

It exposes you to more surprising data.

This ties directly into information theory.

More iterations → higher surface area coverage → a higher chance of luck.

And that “more surprising data” is actually more useful to us

Because it’s what changes our belief systems about the world and the reality we inhabit.

Surprise, Information, and Belief Updating

Think about something as simple as the sun coming up tomorrow.

You’ve already made a prediction that it’s going to happen. There’s almost no new information in that event for you.

Now imagine it raining in the Sahara today, not a common occurrence.

What makes that interesting is there’s a much higher concentration of bits. of information. within that event to learn from.

In information-theoretic terms. surprise is what happens when new data causes a big shift between your prior beliefs and your updated beliefs. Unsurprising events barely move your model of the world. Surprising ones force you to revise

If you’re a perfectionist or a non-iterator, how are you available to see that information?

Because you’re tunnel-visioned into the outcome you want.

Your awareness, expectations, and emotions are siloing you away from the potential to notice that surprising data in the first place.

This is one of the pitfalls of tunnel vision and perfectionistic/neurotic thinking.

Decision Trees, Dogma, and Narrow Paths

When your choice or decision tree is limited, you cap yourself into one way of doing something.

As a result, you’re less likely to run into the non-linear chain of events that would actually expose you to the type of information worth knowing.

An iterative mindset counters this:

• More iterations → more prediction errors

• You figure out what the thing isn’t

• Because you’re more open and spending more time in the “playground” or on the mats

• You’re more likely to pick up that surprising information, high-information “bits”

• That compounds over time, because you’re mathematically ingesting more information about the environment or space you’re in

In the words of Gurdjieff: “If we do what we don’t like doing, the reward must come later. It is a mathematical law and all life is mathematics…..”

Iteration is how you put that exact law to work.

Let’s ground this in health now.

When dogma limits our range of thinking, we are never likely to run into the people, methods, or forms that can actually help us.

If we assume an identity, I’m a pharma guy”, “I’m a holistic/herbal person”, “I’m a doctor”, “I’m an athlete”, that assumed identity becomes a filter.

We start screening out anything that doesn’t fit our belief system. As a result, we decrease our chances of being helped.

Am I saying you should be gullible to every treatment, intervention, or “next big secret” for your health? No.

You can still exercise caution and critical thinking when you surrender your dogma.

The iterative approach is:

• Treat each intervention as an experiment, not an identity.

• Define carefully what you’re measuring (symptoms, labs, performance, mood, sleep, etc.).

• Run small, time-bound trials.

• Update your beliefs based on the data, not the story you or someone else told yourself beforehand.

That’s how you turn health into a learning system instead of a belief system, and its how you see the openness in the world that can actually lead to a healthier way of thinking….

So in short what im trying to say is that IMAGINE finding a method that suggest using an experiment‑based approach increases your exposure to high‑information, belief‑updating events, which in turn makes you smarter, healthier, and luckier over time….

Until next time, thanks for reading Oran/Biohacker..

Welcome to week 13 of the weekly Q&A

Which runs every Wednesday or Thursday depending on how busy I am with my current clients/schedule!

This is your dedicated space for deeper and more useful answers that you wouldn’t or couldn’t normally get on x.

When it comes to bloodwork interpretation, supplement stacks, peptides, bio-regulators, and other fun corners of biohacking

Remember If you want to ask about biomarkers/bloodwork

I’ll break down everything that matters, what it may mean in your context, and what the possible course of action may be for you

Also if I’m unsure about something, I’ll either consult with someone who knows more about the topic

Or I’ll simply say, “I don’t know.”

Biohacker is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.

Topics can include:

• Bloodwork and biomarker interpretation

• Mold exposure/CIRS/sleep etc and other related health questions

• Peptides and bioregulators

• Biohacking and performance optimization

• Diet + nutrition.

• Peptide Sourcing and product questions

• Dosing/Supplement utilization.

• Or if theres anything else you can cook up.

Caveat

I do NOT give medical advice. I ONLY provide guidance, context, and practical direction on the information available, with the goal of helping you make better decisions based on your personal situation.

Unsure how to ask a good question?

Use this infographic i created below to help guide your questions.

Is that everyone just assumes because its pretty simple to be able to ‘take’ a supplement.

That it must also mean theres no underlying frameworks or secret methods that can actually make a difference between a result and getting nothing from them...

Im here to tell you that there is.

Its called timing and understanding the how and why of what your taking.

If you follow me on x.

You might have seen this post from yesterday.

This kind of thinking, wasn’t pulled from thin air.

It came from years of trial and error working with clients who wanted to improve their cholesterol…

And the most interesting part was I didn’t invent it (as much as i would love to take credit for the intelligence)

I stole it from pharmacology.

More specifically, I stole it from how pharmaceutical researchers think about chronopharmacology

Which to remove ambiguity is how the timing of a drug (or supplement) can influence its effect because the biology that it acts on is changing throughout the day, aligned with the circadian rhythm.

The reason im giving you this information is because this concept completely changed my line of thinking, and as a result it helped my clients get better results.

And even now I no longer think about supplements as isolated capsules, but as molecules entering a biological system.

Here’s even a meta question that i ask myself when im designing supplementation/peptide protocols for my 1-1 clients…

That’s the EXACT framework I use.

And this is often the difference between simply taking a supplements, vs designing a supplementation protocol thats geared towards results….

Thanks for reading Oran/Biohacker…

By delivering a handful of actionable tips and mistakes you can avoid so that you don’t waste money within the realms of health/bloodwork.

And don’t worry these will be straightforward

And jargon will be kept to a minimum

Side note: The reason I’m actually writing this post to you, is because over the weekend, an old client of mine put forth a great question (one of those profound ones that gets your head spinning)

“If you had to tell a beginner ten things they should or shouldn’t do before they get bloodwork What would they be”

And so here I am telling you those in realtime.

But before I begin I want to explain something, If i am to highlight all the common mistakes and pitfalls

Then I also want to note that you need to be very careful about getting false positives and letting your brain go into overdrive

Its important with bloodwork that we come in with a non-judgemental/non-emotional approach.

Because the reality is that a result MIGHT not even be true.

Also, an extremely useful heuristic that I hope you can carry into bloodwork interpretation.

Is something you may have learned in high-school/college science.

Can this be actually replicated? And what other markers support the evidence of its truth?

So without further adieu let’s dip into everything that could potentially save you 20+ hours of wasted time, a few thousand $ in false tests, and some anxiety attacks in the process!

1. Testosterone testing and keeping it accurate.

Book your testosterone, LH, FSH, estradiol, and other bloodwork hormonal markers between the hours of 7am-9am.

Why?

Because the morning LH pulse can be 2-3x higher than the trough and 7am-9am is usually the highest pulse of LH, meaning if you miss timing.

You can end up getting an entirely different system state

This is because most men’s testosterone tends to peak around 8AM and drops 25-30% by mid afternoon

Meaning if your consistently running a 3PM draw, then your not getting the most accurate reading that you actually deserve (who would have thought)

(Source: Brener, 1983.)

2. Avoid taking biotin before a blood draw.

Why?

Because biotin supplementation use can actually result in falsely high levels of T4 and T3 and falsely low levels of TSH

Which can lead to false diagnoses of hyperthyroidism, i discovered this after a consult a few years ago when one person in question.

Had drastic changes between two lab results that were very close in proximity. So a big change couldn’t have explained it (i found out he was supplementing biotin)

3. You dont have kidney problems, your just supplementing creatine

This one kind of differs from an actionable tip somewhat, but the point still stands, it’s usually nothing to worry about and it can call for a retest if it really worries you.

Explanation = When you supplement creatine, the metabolic byproduct/converted creatine can make your kidney function appear lower (EGFR)

And this is because some standard kidney tests use creatinine to estimate your EGFR.

So when you supplement creatine it can give you a false low as if to appear that your kidney function has changed.

This is why its important to check other markers such as, Cystatin C, electrolytes, MGR, etc alongside creatine = to prove or disprove the hypothesis.

4. Avoid hard training before you get your bloodwork done!

Why?

Because the enzymes that are measured/attributed to your liver health are also proxies/indicators for muscle damage.

This is why people tend to make the mistake of thinking they have ‘liver damage’ when in reality it’s probably that last superset you did at the gym….

And its reasons like this why nuance is needed with bloodwork…. (photo below reflects the rise)

• AST (aspartate aminotransferase) – present in liver, but also very high in skeletal muscle and heart. Heavy or eccentric training can raise AST substantially for 24–72+ hours.

• ALT (alanine aminotransferase) – is more liver‑specific than AST, but still can rise after intense or prolonged exercise, especially with muscle damage.

Read more

And all too common fallacy within the health and wellness space is the assumption of dosages for drugs/peptides/supplements andresearch chemicals in general.

But they fail to explore the thinking that actually lead to these so called "'defined dosages” in the first place.

Here’s how it tends to play out.

That’s usually how the paradigm starts, but who came to that endpoint/conclusion?

Does another drug which is similar in size/structure have the same starting dose?

Have they scaled animal dosing to match that human dose?

Have they heard it from a friend? Trialled with themselves and others?

No it looks more like a game of copy and paste.

Person A publishes 500 µg. as standard.

Person B copies it.

Person C copies B.

Person D sees 100 people using 500 µg and concludes that 500 µg is now the standard.

This is why you need LARGE scale trials to see what the closer truth dosages really are, and to avoid the cookie cutter protocols that are often handed out by clinics.

Or if anything you may use your own reasoning to come to reach your own conclusion. And if in doubt, then start low and titrate up.

See the thing is when you dose according to what you’ve heard from other people.

You’re adopting the FAFO framework. (Fuck around and find out)

Here’s 3 tips you can actually use when dosing any kind of drug.

1. Toxicology

When you dose any drug, you’re navigating between two critical thresholds:

• Minimum Effective Concentration aka MEC) – the lowest level at which the drug produces the desired effect you’re looking for.

AKA - Ask your monkey brain — what benefits am I looking to achieve with this drug or peptide?

• Minimum Toxic Concentration (MTC) – the level at which harmful effects begin to see.

Ask your monkey brain —— what side effects would I like to avoid.

The space between these is the therapeutic window (or therapeutic index). Good dosing protocols keep plasma concentrations inside this window which are high enough to work, but low enough so that you avoid toxicity.

Let’s call this balance (yin-yang dosing)= low enough so you cant hurt yourself but high enough that you can still see a benefit.

When you defer from these heuristics it leads to FAFO framework as spoken about earlier.

2. Half-life + pharmacodynamics?

Half life (T1/2) is the time of the plasma concentration of the drug to half or fall by 50% during the dosing window.

For example a drug with a half-life of 12/48 hours can be dosed daily, which helps us inform the decisions of how we are going to dose it/keep in our rotation.

Caffeine for example has a short half life but it can be cleared from your system in 6/12 hours but its effects/its pharmacodynamic effects that it has on the body can remain for longer.

(Like why your unable to sleep at night)

3. Pharmacogentics

This means that your genetic phenotype can alter how your process/metabolize drugs.

Which leads to 4 different phenotypes.

• Poor metabolizer = a standard dose of a drug may cause toxicity or more side effects (or benefits) depending on how you frame it.

• Intermeditate metabolizer = may need moderate dose adjustment or a careful titration

• Normal metabolizer = standard dosing protocol tends to be effective, easy to adjust to.

• Ultrafast metabolizer, standard doses are ineffective, and a dose increase or an alternative drug may be needed, depending on how it’s metabolized and which genetics are playing a role.

  ---

  Thats all for me on my daily rant, if you enjoy posts like this and want to learn more, then be sure to make requests (if your a paid sub on the newsletter)

Thanks for reading

Oran/Biohacker.

Which runs every Wednesday or Thursday depending on how busy I am with my current clients/schedule!

This is your dedicated space for deeper and more useful answers that you wouldn’t normally get on x.

Especially when it comes to bloodwork interpretation, supplement stacks, peptides, bio-regulators, and other fun corners of biohacking

Remember If you want to ask about biomarkers/bloodwork

I wont give you vague generalities

I’ll break down everything that matters, what it may mean in your context, and what the possible course of action may be for you

Also if I’m unsure about something, I’ll either consult with someone who knows more about the topic

Or I’ll simply say, “I don’t know.”

Remember the topics can include:

• Bloodwork and biomarker interpretation

• Mold exposure/CIRS/sleep etc and other related health questions

• Peptides and bioregulators

• Biohacking and performance optimization

• Diet + nutrition.

• Peptide Sourcing and product questions

• Dosing/Supplement utilization.

Caveat

I do NOT give medical advice. I ONLY provide guidance, context, and practical direction on the information available, with the goal of helping you make better decisions based on your personal situation.

Unsure how to ask a good question?

Use this infographic below to help guide your questions.

Leave questions on the comment section below :)

I’ve tried hyperbaric oxygen, niche pharmaceuticals, peptides and plenty of other interventions over the years.

So when something genuinely makes me want to run it repeatedly, I tend to pay attention to it….

Back in January, I started deep-diving into some of the Khavinson research and came across Vesugen, a bioregulator peptide that particularly caught my attention because of its proposed relationship with vascular biology.

I’ve been so interested in cardiovascular health for a number of years, partly because I’m an ex-smoker so ive been trying to offset some of my old lifestyle choices

And although i quit five years ago, after years of smoking, I have no way of knowing exactly what cumulative vascular effects occurred In that time.

So when I eventually decided to run Vesugen…

I had a very simple hypothesis, could I actually see a measurable change in my cardiovascular markers?

The primary markers measured were morning blood pressure and resting heart rate.

The blood pressure result really surprised me:

BEFORE: 121/74
AFTER: 117/64

Read more

It made me sad, of course.

I had been with them for almost three years, but it was simply time for a change.

And in that short period, the peptide space has undergone a dramatic shift.

Peptides have transitioned from the RUO underground into mainstream medicines.

With major pharmaceutical companies such as Eli Lilly, Novo Nordisk and other large conglomerates now investing heavily in and adopting these compounds.

And this is because people are beginning to realize just how powerful these drugs can be.

Not even simply as one-off treatments or adjunctives.

But as tools that are truly capable of engineering and restructuring biology in ways that can influence everything from our sleep and fat loss to energy and metabolic function.

Who I Changed To And Why

Meet Peptime.

Yes, I know what you’re probably asking yourself:

What makes them so good/different?

All of their products are compounded in the United States by an exclusive partner pharmacy in Miami, Florida.

And their lyophilized peptides are made in ISO-5 cleanroom conditions with third-party verification.

See, the thing is that producing domestically with peptides means the most fragile part of the journey, getting a finished product safely to your door, never depends on an international shipment clearing customs.

And it means spending less time in transit.

Peptime holds the highest peptide quality grade, Grade A (near pharma grade), across the entire peptide catalog.

And their quality is independently verified by a third-party testing platform that anonymizes the vials, tests them through third-party labs, and assigns each COA a letter grade vendors can’t influence.

Held in temperature-controlled cold storage, all their products are dispatched within 24 hours after order, delivered within 2–3 days.

And their quality is published, independently graded, and traceable by batch.

The Peptides I’m Using, and Why

1. GHK-Cu

GHK-Cu is effectively a bioregulator that can influence thousands of genes involved in inflammation, tissue repair, extracellular matrix, antioxidant defence, and cellular maintenance.

I’m using it because of its potential applications around:

• Redox capacity and mitochondrial antioxidant defence

• Collagen remodeling

• Acne scarring

• Post-surgery scarring

• General tissue repair and cellular maintenance

The reason I’m particularly interested in it is its relationship with collagen remodeling and its broader effects on cellular maintenance.

2. Epithalon (AEDG)

This has helped me to improve my deep sleep numbers for recovery between hard training sessions.

I’ve noticed my deep sleep is slumping on the harder training days where I’m lifting + training BJJ.

So I know was something I want to experiment with.

Recovery becomes a completely different problem when you’re stacking hard lifting sessions with BJJ.

The goal here is simple, Improve the recovery side of the equation.

3. Thymosin Alpha-1

This one was primarily about immune resilience.

I was very immune depleted after training and competing through sickness, and my last lymphocyte/monocyte ratio was on the lower end in my labs.

So Ive been using TA1 once weekly among some other immune peptides/supplements to improve my immune/nervous system balance.

4. Tirzepatide

This one was purely strategic.

I’m currently in the middle of a bulking phase and will be cutting in around 3 weeks to get back down to fighting weight for BJJ at 73 kg.

I’m going to be using some low-dose tirzepatide to aid in the cutting phase and make my life a whole lot easier in the process. (0.8mg)

The goal being to make the process easier while I bring bodyweight back down toward fighting weight…

If You Want To Access Some Of These Peptides

If you want to access some of these peptides, my link is attached below.

Peptime biohacker

You can also use the code BIOHACKER and you’ll get 10% off your total order at checkout.

nt people I’ve met at solving problems in life have all shared a common trait.

It wasn’t until a few years ago that I became fully aware of what this particular trait actually was.

I first seen this in my grandfather, then in those who worked in medicine/clinicians, engineers and within a few functional medicine practioniers (at least the good ones)

They could all walk into problems with very little information the build a working hypothesis that rewarded them with the most unusual ability to figure things out and evidently solve the puzzle…

And this is because they suspended ‘knowing’ and instead of simply believing that they knew the answer immediately or brought their prejudices/dogma into each equation

Instead they asked themselves.

1. What do we actually know?

2. What don’t we know?

3. What could actually explain this?

4. What are the competing explanations?

Then most importantly:

What would else would I need to see to change my mind?

I also noticed the emotional pattern that they weren’t trying to be right for right-sake

But they were trying to simply trying to become LESS wrong and actually solve the root of the problem.

Read more

I’ve picked up the old habit of writing every day.

The purpose of this is not to produce anything perfect, but quite simply to get back into a groove.

A distinction that matters because, like so many others I can be incredibly hard on myself when it comes to anything I pursue.

I suspect this comes from having a particularly strong superego, an inner voice that is constantly evaluating, correcting and demanding more. (which happens with thinky/analytic types)

And If I’m not careful, the same voice can siphon the enjoyment out of almost anything I do.

I’ve spent a lot of time in performance-based environments, amateur football, Brazilian jiu-jitsu, Muay Thai and various different forms of self-development. (that I won’t get into)

And while these domains taught me discipline, resilience and the value of pursuing ambitious goals

They also taught me to somewhat associate my progress with an outcome…

Instead of enjoying the process of what we do, we end up constantly measuring ourselves against an imagined future version of who we think we should be.

Which can reduce the presence and awareness required to perform well in the first place

And paradoxically, becoming overly fixated on results makes it harder to achieve them anyway.

Because outcomes are only downstream of the effort and process we place into them.

This is where micro-goals become so valuable. (at least for me)

A micro-goal is a deliberately small action that is almost impossible to fail at.

It may seem laughable compared with the final objective or the end product you often see on social media.

But that is precisely the point, its supposed to get you started without triggering any unnecessary resistance or self-judgment.

Want to become a world champion in Brazilian jiu-jitsu? Start with one competition class per week.

Want to become stronger? Do half a pull-up or one pull up per day. (depending on your strength)

Want to improve your health? Walk for ten minutes after dinner. (postprandial glucose walk)

Want to write consistently? Write one paragraph. (works for me)

The goal is obviously not to remain at this level forever, but to use the goa to create enough consistency for momentum, confidence and capacity to develop naturally. (and build a habit)

Micro-goals are magic doors because they lower our psychological cost of starting, and they transform progress from something that requires heroic effort into something you can repeat EVEN on the most imperfect day.

And repetition is where change happens (especially neuroplasticity)

This also applies particularly well to health, Ive met so many people who approach their health with an all-or-nothing mentality

Completely change their diet, train six days per week, optimise every supplement, sleep perfectly and never miss a session.

And that approach may be motivating for a short period and for some people

But it is often difficult to sustain. A better starting point for a beginner might be.

• Drink one additional glass of water.

• Eat one serving of protein with breakfast.

• Take a ten-minute walk.

• Go to bed fifteen minutes earlier.

• Complete one rep of an excercise.

• Prepare one healthy meal.

These actions may not appear significant in isolation, but they create evidence that you are the kind of person who follows through. (identity shift).

Over time, the micro-goal can expand into more, one pull-up becomes three, ten minutes of walking becomes thirty, one paragraph ends up becoming a page.

The important thing for you is that the habit is built well before you increase the demand.

And dont try to think that the ambitious goals still matter because they do provide you with a destination

But micro-goals help you determine whether you keep moving when motivation disappears and when becomes life becomes chaotic or your inner critic starts telling you that the small progress is not good enough.

I hope you enjoyed reading and you start today with a small micro-goal to bring you closer to your ideal reality.

Thanks Oran/Biohacker.

I noticed this recently when someone sent me their bloodwork.

They complained of poor drive and almost ADHD-like symptoms.

Where they once could concentrate and focus for hours, they could now barely manage ten minutes. They had gut irritation. A fogginess completely unlike their old default.

It wasn’t until I did a deep dive that I could begin to synthesize a hypothesis for what had actually occured.

And as I slowly dropped down into Wonderland, I realized I was looking at a nutrient absorption problem that started in the gut. But finished in the brain. As all do.

Their bloodwork showed what looked like an iron deficiency. But they ate a diet rich in iron. Their creatinine levels indicated high protein turnover. So I had no reason to question their intake.

Looking deeper, I saw they were allergic to gliadin — the protein in gluten.

That’s when the cascade clicked into place.

Here’s what was actually happening:

Read more

Merck just made a MAJOR move.

They’ve developed and secured approval for an oral PCSK9 inhibitor enlicitide decanoate (formerly MK-0616 in the development trials, now marketed as Lipfendra).

And it could capture a large portion of the cholesterol market, But its also important to remember

Lipfendra isnt your conventional small-molecule drug that most oral pharmaceuticals in development usually are.

Instead, it’s an orally bioavailable macrocyclic peptide that binds PCSK9

The exact protein that destroys your LDL receptors.

Here’s how that cascade works in practice:

1. LDL receptors sit on your cells and pull LDL out of your blood. They recycle around 150 times before being degraded.

2.PCSK9 (a secreted protease, mostly made by your liver) binds the EGF-A domain of LDLR and tags it for lysosomal destruction, which means no more recycling from those LDL receptors.

3. Because Lipfendra inhibits PCSK9 → more LDLR survive → more LDL gets cleared from plasma.

Call that utilising the BODY against itself.

But how does the oral differ from the injectable? You’re probably asking yourself and are they as effective? What are the limitations of both?

>>> Repatha (evolocumab) — injectable:

- Full monoclonal antibody (~150 kDa)

- Binds the EGF-A domain of PCSK9 with picomolar affinity — essentially irreversible

- Stays in circulation for ~11–21 days

- Every molecule of PCSK9 it encounters gets neutralised, wherever it may be in the body

>>> Lipfendra (enlicitide decanoate) — oral:

- Oral cyclic peptide (~2 kDa — 1/75th the size of the mAb)

- Same target: binds PCSK9 at the LDLR interface

- But instead it’s absorbed through the gut (bioavailability of ~10–20%)

- Short half-life (~10–15 hours) → daily dosing required

- Works systemically once absorbed*, but the gut absorption window constrains everything

How effective is it?

Surprisingly close to Repatha, based on the studies that is.

Comparing oral to injectable reduction.

The LDL-lowering is essentially comparable

The mAbs don’t tend to win on the raw LDL reduction

Which is surprising given the pharmacokinetic gulf between both drugs.

The real limitations of the oral

1) Daily dosing vs every 2–4 weeks

This is the biggest trade-off. The mAbs (like Repatha) win on convenience i you’re okay with needles, you don’t need repeated dosing. Lipfendra is a daily pill.

So you’re essentially trading injection anxiety for pill fatigue.

2) Food effect

Lipfendra had a significant food interaction in Phase II trials — so you need to take it on an empty stomach.

3) No long-term data

Repatha/Praluent have >10 years of real-world data — cardiovascular outcomes (FOURIER, ODYSSEY OUTCOMES), safety in millions of patient-years. Lipfendra has Phase II with ~400 patients for ~8 weeks.

So the large safety data doesn’t exist at scale yet.

4) Lp(a) reduction is sliglty inferior

This matters. The ~10–15 point difference in Lp(a) reduction between Lipfendra and Repatha isn’t trivial. Lp(a) is an independent causal risk factor, and it’s notoriously hard to lower. If the oral loses ground here, the high-Lp(a) patient gets less benefit.

5) Manufacturing complexity

Cyclic peptides aren’t cheap pills to manufacture. Solid-phase peptide synthesis at commercial scale can be expensive. Lipfendra won’t be Lipitor pricing

It’ll likely sit somewhere between generic statins and branded mAbs. The pricing calculus is uncertain at the moment.

Where the oral wins (whatever winning is)

- No injection, the obvious one, and it captures that 25% who refuse needles

- No cold chain --- transforms distribution in developing markets

- Potentially lower manufacturing cost than mAb bioreactors (though not by as much as people assume)

- Patient preference early surveys have shown ~70% of patients would prefer an oral over an injectable if the efficacy and cost were equal

The bottom line

Lipfendra matches Repatha on the number that matters most, LDL, but loses ground on Lp(a), the convenience frequency, and the safety confidence that only a decade of outcomes data can actually buy.

And the split decision comes down to if the needle is the barrier or the pill is for you.

Thanks for reading.

Oran / Biohacker

Welcome to week 11 of the weekly Q&A

Which runs every Wednesday or Thursday depending on how busy I am with my current clients/schedule!

This is your dedicated space for deeper and more useful answers that you wouldn’t normally get on x.

Especially when it comes to bloodwork interpretation, supplement stacks, peptides, bio-regulators, and other fun corners of biohacking

Remember If you want to ask about biomarkers/bloodwork

I wont give you vague generalities

I’ll break down everything that matters, what it may mean in your context, and what the possible course of action may be for you

Also if I’m unsure about something, I’ll either consult with someone who knows more about the topic

Or I’ll simply say, “I don’t know.”

Remember the topics can include:

• Bloodwork and biomarker interpretation

• Mold exposure/CIRS/sleep etc and other related health questions

• Peptides and bioregulators

• Biohacking and performance optimization

• Diet + nutrition.

• Peptide Sourcing and product questions

• Dosing/Supplement utilization.

Caveat

I do NOT give medical advice. I ONLY provide guidance, context, and practical direction on the information available, with the goal of helping you make better decisions based on your personal situation.

Unsure how to ask a good question?

Use this infographic below to help guide your questions.

Isnt the purpose of data to enable better-informed decisions?

Then why should your health data be any different?

You see it all the time. genetics tests. Whoop. Weightlifting logbooks. Bloodwork.

You gather information from everywhere --- and then it goes into a spreadsheet, an obsidian note, or a PDF that sits in a folder, never to be touched again.

Or as i like to call it the dead sea scrolls of health data.

What’s the point of collecting this data if it never informs a single one of our decisions?

Take traders. They don’t aggregate data to feel smart. (well some of them dont)

They do it to make better trades and MORE money.

That’s the whole point. Data has a job. The moment your data stops doing its job, its no longer intelligence.

It’s clutter.

This question has been nagging me for weeks. It makes me viscerally angry.

Because if you’re like me, you’ve probably fallen into this trap before.

The trap is collecting for the sake of collecting, the illusion of progress

The comfort of a full dashboard. But the objective was never to have data for datas sake and somehow we all lost ourselves along the way.

The objective is to fill the unknowns so you can make more informed decisions, to either prevent disease UPSTREAM, improve performance, or improve health.

And If your data doesn’t feed ONE of those three decisions, it’s vanity and status signalling.

And you’re mentally masturbating with data collection. (call that collection porn)

Well then smart arse whats the alternative and how do i fix it?

First, don’t go solution-first.

Everyone wants a quick protocol, supplement, the hack they found on a reddit forum in 2017.

But the best thing you can do is stop and ask

What problem am I actually trying to solve? (name it)

When my ferritin is flagged low, my instincticual monkey brain is telling me to take iron supplements.

The real question isnt supposed to be what do I take

Its why is the ferritin dropping?

Maybe its the fact you havent had an iron rich meal in two weeks after a blood-donation donald.

2) Second, let the other data speak before you rush

A single metric is almost NEVER the whole story.

Lets say your resting heart rate has crept up for a month. You could fixate on that number. Or you could look at what was happening in the weeks before it moved. worse sleep quality, higher training load, a stressful stretch at work because karen from HR is giving you jip

The heart rate spike is the last thing to show up in trends.

The drivers and the decisions you made showed up weeks earlier, and its important to remember that the symptom tells you there’s a fire somewhere

But the rest of the data tells you where that fire started.

3) Third, contextualize, then constrain. What’s the context? Is this lifestyle-fixable, sleep, nutrition, training, recovery, stress

Or does it need actual intervention, pharma, a lab panel, a doctor? Be honest about the difference.

Then remove optionality for ambiguity’s sake. Don’t change your sleep, your diet, AND your supplements in the same week, now you don’t know what worked. Change one thing. observe it. Only then move the next levers. One variable at a time is slow-feeling but it’s the only way you ever actually learn what works.

The more time you spend nailing a problem down, the more likely you are to fix it. and haste is just expensive trial-and-error.

Thats all from me for today.

Oran/Biohacker.

The genes are still there of-course

But they are laying dormant and something is blocking them

And that something can be indeed be UNLOCKED.

(according to the russians that is)

This is because the actual DNA sequence

Stays largely intact throughout your life from the moment you’re born until the day you die

The problem is that your instructions slowly disappear, and the elegant machinery that reads those instructions stops working over time.

This is where chromatin comes in

The DNA gatekeeper that none of you have probably heard of, inside every cell in your body sits roughly two metres of DNA(quite long when you think about it)

So your cells solve this problem/length with a very elegant packaging system.

DNA wraps around proteins called histones to form structures called nucleosomes

And those nucleosomes coil and fold into chromatin fibres

And when the cell divides, chromatin condenses further still into the chromosomes and you probably recognize this from highschool/college biology class.

But chromatin is not just there to store information It’s also a control system.

Tightly packed chromatin. called heterochromatin physically hides your DNA from the cellular machinery that reads it.

Where loosely packed chromatin, called euchromatin then exposes it, making genes accessible for transcription

Which is the process of copying DNA into RNA, which then gets translated into proteins.

Think of it in this simple way:

Tightly packed chromatin = your DNA is hidden.

Loosely packed chromatin = your DNA is more accessible.

This is why researchers often call chromatin the gatekeeper of gene expression.

Before any gene can be expressed, before any protein can be made chromatins structure has to permit that process.

Here’s where it gets super important and why you need to keep reading.

As you age, your chromatin progressively dysregulates.

Some regions that were once open and actively transcribed shift into heterochromatin, tightly packed, inaccessible, silent.

Others that should remain silent become active, driving inflammation and cellular dysfunction.

This is called heterochromatinisation, and it’s one of the most underappreciated drivers of biological aging.

The genes themselves haven’t mutated, and the actual code is still there.

But the machinery can no longer reach the right regions at the right times.

Ribosomal genes, the ones responsible for protein synthesis start to fall silent, metabolic pathways slow down and tissue-specific functions decline with time.

So you can think of it in a way that your body doesn’t forget how to function well

It just loses access to the instructions that once gave it the power to

Which is where peptide bioregulators come in.

Peptide bioregulators, particularly the short di- tripeptides and tetrapeptides developed through Khavinson’s decades of research

Specifically target something called selective deheterochromatinisation

Which is the targeted reopening of condensed chromatin in specific chromosomal regions.

Peptides like Vesugen (KED) and Vilon are small enough to enter the nucleus and interact directly with DNA promoter regions and histone proteins, particularly H1 and H3. and by doing so, they can shift localised chromatin from a condensed, transcriptionally silent state back toward more open euchromatin.

The result = genes that had gone quiet after decades of dormancy with age become slowly become accessible again = transcription factors and RNA polymerase can reach the DNA.

= Protein synthesis resumes as normal to youthful levels.

In the case of Pinealon- the target is the pineal gland’s AANAT enzyme the rate-limiting step in melatonin synthesis.

Age-related heterochromatinisation silences the genes regulating AANAT expression.

Pinealon’s proposed mechanism is reopening protein function to restore more youthful melatonin output.

In the case of Vesugen another peptide (KED) the targets include vascular and cardiovascular gene networks. Research shows this peptide can.

- Enhances mesenchymal stem cell proliferation

- Reduces senescence markers and SASP-like inflammatory secretory profiles

- Modulates Ki-67 and other proliferation-related genes in vascular cells

- May upregulate SIRT1 — a central longevity regulator

A small human trial using Pinealon and Vesugen in polymorbid patients aged 41–83 CNS-improving effects, alongside a slower rate of increase in biological age indices.

Vesugen also showed stronger geroprotective effects on the measured markers.

Notably, these epigenetic effects can persist even after the peptide course ends, because you’ve actually changed the chromatin architecture

Not just temporarily flooded a receptor like other peptides do.

How Khavinson Found Them

Most peptide research starts with a hypothesis and works toward one certain molecule.

Khavinson’s approach was different.

He started with tissue. Specifically, organ-derived proteins. from the pineal gland, thymus, heart, cartilage, vascular tissue.

Big K

He would isolate and hydrolyze these proteins, breaking them down into their smallest functional fragments, then identify which fragments retained biological regulatory activity

What he found were di and tripeptides tetrapeptides sequences of just two or three/four amino acids, that appeared to be naturally embedded within larger protein structures.

Fragments that the body itself can understand and that appear to function as signaling molecules in their own right.

The implication is significant, these peptides may represent the body’s own internal regulatory language.

Short sequences that can communicate state, trigger gene expression, and modulate chromatin. all from within the natural lifecycle of proteins.

The Lysine Patter

Here’s where things gets interesting.

Across Khavinson’s library of bioregulators i seen a pattern emerg. At least 60% of the most relevant bioactive peptides contain lysine specifically at either the start or the end of their sequence.

Look at some of the most studied compounds:

- Vilon (Lys-Glu). starts with lysine

- Vesugen/KED (Lys-Glu-Asp) starts with lysine

The lysine dominance has a mechanistic reason for it.

Lysine carries a positive charge at physiological pH. DNA carries a strong negative charge, from its phosphate backbone. Opposites attract. Positively charged amino acids have a natural electrostatic affinity for DNA, which is precisely why histones themselves are extraordinarily rich in lysine and arginine.

Their positively charged tails grip the negatively charged DNA to form nucleosome structure.

So when short peptides containing lysine enter the nucleus and interact with histones, they’re not doing something foreign to the system, they’re just speaking the native language of the body.

A Heuristic for future discovery of new peptides.

This pattern matters beyond the existing peptide library that we have.

If lysine at the terminal position is a recurring feature of biologically active chromatin-modulating peptides, and the mechanistic reason for that is the electrostatic affinity for DNA and histone interaction sites

Then you have the beginnings of a discovery heuristic.

Future tissue-derived peptide fragments containing terminal lysine residues become candidates worth screening first.

It doesn’t guarantee that there will be activity, but it narrows the search space considerably. In a field where the combinatorial space of even tripeptides is in the thousands, a structural rule that eliminates false candidates early has serious research value.

This is how science naturally progresses by trying to avoid the random screening of millions of molecules

But through more mechanistic/targeted insight that generates testable predictions.

Hope you enjoyed the read Oran/Biohacker.

Which runs every Wednesday or Thursday depending on how busy I am with current clients/schedule.

This is your dedicated space for deeper and more useful answers that you wouldn’t normally get on x.

Especially when it comes to bloodwork interpretation, supplement stacks, peptides, bio-regulators, and other fun corners of biohacking

Remember If you want to ask about biomarkers/bloodwork

I won’t just give you vague generalities.

I’ll break down everything that matters, what it may mean in your context, and what the possible course of action may be for you

Leave your questions in the comment section below and I’ll answer them.

Also if I’m unsure about something, I’ll either consult with someone who knows more about the topic

Or I’ll simply say, “I don’t know.”

Remember the topics can include:

• Bloodwork and biomarker interpretation

• Mold exposure/CIRS/sleep etc and other related health questions

• Peptides and bioregulators

• Biohacking and performance optimization

• Diet + nutrition.

• Peptide Sourcing and product questions

• Dosing/Supplement utilization.

Caveat

I do NOT give medical advice. I ONLY provide guidance, context, and practical direction on the information available, with the goal of helping you make better decisions based on your personal situation.

Unsure how to ask a good question?

Use this infographic below to help guide you.

Welcome to Week 9 of the weekly Q&A, which runs every Wednesday or Thursday depending on how busy I am with current clients/schedule.

This is your dedicated space for deeper and more useful answers that you wouldn’t normally get on x.

Especially when it comes to bloodwork interpretation, supplement stacks, peptides, bio-regulators, and other fun corners of the biohacking sphere

Remember If you want to ask about biomarkers, I won’t just give you vague generalities.

I’ll break down everything that matters, what it may mean in your context, and what the possible course of action will be for you

Leave your questions in the comment section below and I’ll answer them.

Also if I’m unsure about something, I’ll either consult with someone who knows more about the topic, or I’ll simply say, “I don’t know.”

Remember the topics can include:

• Bloodwork and biomarker interpretation

• Mold exposure/CIRS/sleep etc and other related health questions

• Peptides and bioregulators

• Biohacking and performance optimization

• Diet + nutrition.

• Peptide Sourcing and product questions

• Dosing/Supplement utilization.

Caveat

I do NOT give medical advice. I ONLY provide guidance, context, and practical direction on the information available, with the goal of helping you make better decisions based on your own situation.

Unsure how to ask a good question?

Use this infographic below to help guide you.

We’ve all heard the claim just eat lean ground beef or low fat based foods and you wont get fat

But this assumes that theres direct causality between fat intake and what your body does it with it

As if theres an imaginary linear chain that exists in something as complex as the human body.

But each individual is different, and the chain is never as simple as we think.

Because the true driver of fat accumulation is how your body partitions and utilizes the fuel it receives.

And another real truth is when your metabolic machinery is optimized

High dietary fat will simply become another high-octane energy source rather than being stored adipose tissue.

I know this because an athlete i can push fat intake extremely high and stay lean. even when im in a surplus.

The Key Role of Metabolic Flexibility in the process.

Metabolic flexibility is the ability of your mitochondria to toggle seamlessly between oxidizing glucose and burning fatty acids via beta-oxidation.

In a metabolically inflexible person, the mitochondria struggle to make this switch, leading to elevated blood glucose, chronic insulin spikes, and the inevitable storage of excess energy as fat.

When you are metabolically flexible, your body efficiently taps into circulating lipids and stored fat for ATP production during rest or lower-intensity activities

This keeps your fat oxidation rates high and prevents dietary fat from spilling over into fat storage.

Lets give 2 examples of that in real time.

Greg who works at the office and whos insulin resistant. he eats lots of fat and lots of carbs, greg is metabolically inflexible and the excess carbs and fats end up being shuttled into adipose tissue because they aren’t being sent anywhere. he has no muscle mass and his mitochondria havent heard of fat burning since 1977 when he played baseball in junior high.

Then theres Michael

Michael is an athlete who does regular zone 2 work and has a high step count and has alot of muscle mass, he can get away with high fat/high carbs because theres a place to put it.

Because the truth is, theres no evil nutrients. only what you and your body do with them.

In comes Insulin Sensitivity and nutrient partitioning

Insulin sensitivity dictates where your nutrients go after consumption, a process known as nutrient partitioning.

When you have high insulin sensitivity particularly in skeletal muscle your muscle tissue acts as a massive metabolic sink

Nutrients are shuttled directly into muscle cells to replenish intramuscular triglycerides and glycogen or to repair tissue

If you are insulin resistant on the other-hand , muscle cells reject these nutrients, forcing the liver to route them directly into adipocytes.

Why It Must Be Earned

Pushing dietary fat to the upper limit while staying lean requires a highly developed metabolic engine that takes time and effort to build

Because you have to create the cellular demand through heavy strength training and rigorous cardiovascular outputs,.

These activities deplete cellular energy stores and trigger mitochondrial biogenesis, increasing the sheer number and density of mitochondria available to burn fuel.

By building a large base of lean muscle mass and keeping body fat low, you maximize insulin receptor density and lock in that metabolic flexibility

Allowing your body to run like a furnace even with a high fat intake.

FOOTNOTE.- this free article was written by me and all analogy are of my own understanding

Claude has thankfully Aided me with the visuals so that i can get my understanding into visual form.

Welcome to Week 8 of the weekly Q&A, which runs every Wednesday or Thursday depending on how busy I am with current clients/schedule.

This is your dedicated space for deeper and more useful answers that you wouldn’t normally get on x.

Especially when it comes to bloodwork interpretation, supplement stacks, peptides, bio-regulators, and other fun corners of the biohacking sphere

Remember If you want to ask about biomarkers, I won’t just give you vague generalities.

I’ll break down everything that matters, what it may mean in your context, and what the possible course of action will be for you

Leave your questions in the comment section below and I’ll answer them.

Also if I’m unsure about something, I’ll either consult with someone who knows more about the topic, or I’ll simply say, “I don’t know.”

Remember the topics can include:

• Bloodwork and biomarker interpretation

• Mold exposure/CIRS/sleep etc and other related health questions

• Peptides and bioregulators

• Biohacking and performance optimization

• Diet + nutrition.

• Peptide Sourcing and product questions

• Dosing/Supplement utilization.

Caveat.

I do NOT give medical advice. I ONLY provide guidance, context, and practical direction on the information available, with the goal of helping you make better decisions based on your own situation.

Unsure how to ask a good question?

Use this infographic below to help guide you.