The Collagen Paradox: A Deep Dive into Protein Science by Dr. Rick Cohen, M.D.

The Collagen Paradox

Or: The Amino Acid Hierarchy Your Mitochondria Actually Care About

The Setup

You're told to eat protein. Get your amino acids. Maybe supplement BCAAs if you lift.

But then there's collagen—which is protein, technically, but a weird one. It's mostly glycine, proline, and hydroxyproline. Not the "complete protein" you're told to prioritize.

Yet collagen supplementation works. Skin, joints, gut, sleep, recovery—it all improves.

And here's the paradox: You can synthesize collagen. Your body makes it constantly. So why the hell would you need to eat it?

Let's solve this through the mitochondrial framework, because the answer reveals something profound about what your ancient bacteria actually prioritize.

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Part 1: Not All Amino Acids Are Equal To Your Mitochondria

We covered that you need external amino acids because you can't synthesize the essential ones (the nine you must eat).

But here's what nobody emphasizes:

Your mitochondria don't care about all amino acids equally.

Some amino acids are metabolically expensive to make. Some are required in massive quantities. Some are needed for mitochondrial structure itself.

The amino acid hierarchy from the mitochondrial perspective:

Tier 1: The Ones You Literally Cannot Make

Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine

These are "essential" because the synthesis pathways are completely gone. You eat them or you die.

Tier 2: The Ones You Can Make But It Costs Too Much

Glycine ← THIS IS THE KEY

Proline

Arginine (conditional)

Cysteine (conditional)

These are "non-essential" in textbooks, meaning you won't die without dietary intake. But that doesn't mean you can make enough for optimal function.

Tier 3: The Ones You Make Easily

Alanine, aspartate, asparagine, glutamate, glutamine, serine

Your body makes these readily from other metabolites. Dietary intake is bonus, not requirement.

Part 2: Glycine Is The Bottleneck

Here's the thing about glycine that breaks the entire "non-essential amino acid" framework:

You need approximately 10-15 grams per day for basic structural turnover.

You can synthesize approximately 2-3 grams per day.

Gap: 7-12 grams per day.

This isn't a small discrepancy. This is a structural deficit that you're supposed to make up through diet.

Why do you need so much glycine?

Because glycine is the most abundant amino acid in collagen, and collagen is the most abundant protein in your body.

30% of total body protein is collagen

Collagen is 33% glycine by composition

You're not just maintaining muscle. You're maintaining:

Skin (constant turnover)

Gut lining (3-5 day turnover)

Blood vessels (endothelial repair)

Connective tissue (ligaments, tendons, fascia)

Bone matrix (organic scaffold)

Cartilage (joint surfaces)

Every single one of these tissues is primarily collagen. And collagen is primarily glycine.

Your body is trying to build collagen at a rate that requires more glycine than you can synthesize.

Part 3: The Mitochondrial Glycine Connection

Now here's where it gets wild:

Glycine isn't just a structural amino acid. It's a direct mitochondrial signaling molecule.

Glycine and Mitochondrial Function:

Heme synthesis happens in mitochondria

Glycine + succinyl-CoA → δ-aminolevulinic acid (ALA)

ALA → heme (the core of hemoglobin, myoglobin, cytochromes)

Every cytochrome in your electron transport chain requires heme

No glycine = impaired heme synthesis = dysfunctional electron transport

Glutathione synthesis requires glycine

Glutathione = γ-glutamyl-cysteinyl-glycine

Master antioxidant protecting mitochondrial membranes

Without adequate glycine, glutathione synthesis is limited

No glycine = impaired antioxidant defense = mitochondrial oxidative damage

Glycine acts as an inhibitory neurotransmitter

Calms neuronal firing

Improves sleep quality

Reduces excitotoxicity

This is why glycine supplementation improves sleep—it's not just "relaxing," it's reducing neuronal energy demand, giving mitochondria recovery time

Glycine regulates mitochondrial respiration directly

Recent research shows glycine affects Complex I activity

Modulates mitochondrial calcium handling

Influences mitochondrial membrane potential

Glycine isn't optional for mitochondria. It's foundational.

Part 4: Why Collagen Specifically?

Okay, but you could just supplement glycine powder, right?

You could. But collagen provides something more:

Collagen delivers glycine in the ratios your body is trying to build.

Collagen is approximately:

33% glycine

12% proline

11% hydroxyproline

10% glutamic acid

Plus small amounts of other amino acids

When you consume collagen, you're providing the exact amino acid profile your body needs to synthesize collagen.

This matters because collagen synthesis is the rate-limiting step for structural repair.

If you're glycine-deficient but have excess leucine (from whey protein), your body can't just convert leucine to glycine. The pathways don't work that way.

You need the right amino acids in the right ratios.

Collagen peptides are also uniquely bioavailable.

When you eat collagen, it breaks down into:

Individual amino acids (glycine, proline, etc.)

Di-peptides and tri-peptides (small chains)

Those small peptides (especially glycine-proline-hydroxyproline combinations) appear in your bloodstream intact and can be directly incorporated into tissues.

Studies show that after collagen consumption:

Specific collagen-derived peptides appear in skin

Fibroblasts (cells that make collagen) increase activity

Collagen synthesis markers increase

You're not just providing raw materials. You're providing pre-assembled components that your cells recognize and use directly.

Part 5: Why We Need External Collagen (The Evolutionary Answer)

Here's the ultimate question: If collagen is so important, why didn't we evolve to synthesize enough glycine?

Answer: We did evolve to get it externally.

Historical human diets were collagen-rich:

Bone broth (collagen-rich connective tissue simmered for hours)

Organ meats (connective tissue attached)

Skin (chicken skin, fish skin, pork rinds)

Cartilage (eating whole animals, bones and all)

Bone marrow (contains collagen matrix)

Our ancestors ate the entire animal. Nose-to-tail. Every culture had bone broth or similar preparations.

Modern Western diet:

Muscle meat only (low in glycine, high in methionine)

No skin, no bones, no connective tissue

No bone broth

We evolved expecting dietary collagen, so we didn't need to synthesize as much glycine.

Same pattern as essential amino acids, B vitamins, and every other "external mitochondria" compound:

Evolution is ruthless about efficiency. If you're getting something reliably from diet, you lose the ability to make it yourself.

We kept some glycine synthesis (unlike essential amino acids where we lost it completely), but not enough for optimal function without dietary collagen.

Part 6: The Methionine-Glycine Balance

Here's a piece that ties directly to mitochondrial health:

Muscle meat is high in methionine, low in glycine.

Methionine is an essential amino acid (you need it), but too much methionine without balancing glycine creates problems:

Methionine metabolism produces homocysteine:

Homocysteine is pro-inflammatory

Elevated homocysteine increases cardiovascular risk

Homocysteine damages mitochondria directly

Glycine helps clear homocysteine:

Glycine + serine → conversion of homocysteine back to methionine or cysteine

Adequate glycine keeps the methionine cycle balanced

Low glycine = homocysteine accumulation = mitochondrial stress

Modern high-muscle-meat diets create a methionine-glycine imbalance.

You're getting tons of methionine (from chicken breast, steak, protein powder) but minimal glycine (no skin, bones, or connective tissue).

Result:

Elevated homocysteine

Increased oxidative stress

Mitochondrial dysfunction

Accelerated aging

Adding collagen rebalances the ratio.

Part 7: What About BCAAs? (Why They're Overrated From This Framework)

BCAAs (branched-chain amino acids) = leucine, isoleucine, valine.

The fitness industry loves them because leucine triggers mTOR (muscle protein synthesis signaling).

But from the mitochondrial perspective:

BCAAs are primarily about signaling, not building.

Leucine tells your cells "build muscle." But it doesn't provide the materials to build optimally if you're deficient in glycine, proline, or other structural amino acids.

BCAAs are preferentially oxidized in muscle.

Unlike other amino acids that go to the liver first, BCAAs get metabolized directly in muscle tissue—including in muscle mitochondria.

This provides energy during exercise, but chronic BCAA supplementation without adequate glycine creates the same methionine-glycine imbalance problem.

BCAAs don't address the structural deficit.

If your body is trying to repair:

Gut lining (collagen-based)

Blood vessels (collagen-based)

Skin (collagen-based)

Joints (collagen-based)

...then extra leucine doesn't help, it hurts! You need glycine, proline, hydroxyproline—the stuff collagen is made of.

BCAAs are useful for muscle protein synthesis signaling, but they don't solve the deeper structural and mitochondrial needs.

Part 8: The Inside Protein Framework - What Matters Most

Let's rank the amino acids by mitochondrial priority:

Tier 1: Mitochondrial Function

Glycine - Heme synthesis, glutathione, direct mitochondrial signaling

Cysteine - Glutathione synthesis, iron-sulfur cluster assembly

Methionine - Methylation, SAMe production, but needs glycine balance

Tier 2: Structural Integrity That Protects Mitochondria

Proline - Collagen synthesis (with glycine)

Lysine - Collagen cross-linking, carnitine synthesis

Threonine - Mucin production (gut barrier), immune function

Tier 3: Energy Metabolism

Leucine - mTOR signaling, BCAA oxidation in muscle

Isoleucine - Glucose uptake, BCAA oxidation

Valine - BCAA oxidation, branch point for other pathways

Tier 4: Specialized Functions

Tryptophan - Serotonin, melatonin, NAD+ synthesis

Histidine - Carnosine synthesis (muscle buffer), histamine

Arginine - Nitric oxide synthesis, immune function

Notice what's at the top: glycine and cysteine—the amino acids required for glutathione and heme.

Your mitochondria prioritize their own protection and function over muscle building.

Part 9: The Collagen Protocol (What Actually Works)

Based on this framework:

Minimum effective dose: 10-15g collagen per day

This provides:

~3-5g glycine

~1-2g proline

Balance of other amino acids in collagen ratios

Best sources:

Bone broth protein powder

Delivers collagen + minerals from bones + glycosaminoglycans

Most bioavailable form

Collagen peptides (hydrolyzed collagen powder)

Convenient, highly bioavailable

Mix into coffee, smoothies, water

Gelatin (intact collagen, gels when cooled)

Slightly less bioavailable than peptides

Good for gut healing (coats intestinal lining)

Whole-animal eating (skin, cartilage, connective tissue)

Chicken skin, pork rinds, fish skin

Traditional "nose-to-tail" approach

Timing considerations:

Before bed:

Glycine improves sleep quality

Mitochondrial repair happens during sleep

Providing building blocks at night supports overnight tissue repair

Post-workout:

Collagen supports connective tissue repair

Combines well with vitamin C (required for collagen synthesis)

With meals:

Balances methionine from muscle meat

Supports gut lining integrity

Synergistic compounds:

Vitamin C (cofactor for collagen synthesis):

Required to convert proline to hydroxyproline

Required for collagen cross-linking

Without adequate vitamin C, collagen synthesis fails (this is scurvy)

Copper (lysyl oxidase cofactor):

Required for collagen cross-linking

Creates the strong bonds between collagen fibers

Deficiency = weak connective tissue despite adequate collagen

Glycine alone (for mitochondrial support):

3-5g glycine before bed improves sleep

Supports glutathione synthesis

Cheaper than collagen if structural repair isn't the primary goal

Part 10: The Unifying Theory of Protein

Let's bring this full circle with everything we've learned:

Your body, or rather mitochondria and cells, are most run by ancient bacteria with ancient requirements.

Those requirements include:

Metals for electron transport (iron, copper, magnesium)

Cofactors for enzymatic function (B vitamins, CoQ10)

Signaling molecules (nitrate → NO)

Amino acids they can't make (all nine essential)

Amino acids they can't make enough of (glycine, primarily)

Glycine is special because it serves triple duty:

Structural (collagen, 30% of body protein)

Mitochondrial (heme synthesis for electron transport)

Protective (glutathione synthesis for antioxidant defense)

You need external collagen/glycine because:

Your synthesis capacity (~2-3g/day) doesn't match demand (~10-15g/day)

You evolved eating whole animals rich in collagen

Modern diets provide excess methionine with insufficient glycine

Your mitochondria require glycine for their own function, not just structural needs

This isn't about "collagen for beauty" or "BCAAs for gains."

This is about providing your mitochondria the amino acids they prioritize:

Glycine for heme (electron transport depends on it)

Glycine for glutathione (mitochondrial protection depends on it)

Cysteine for the same reasons

Complete essential amino acids for protein synthesis

When you eat collagen, you're not "supplementing."

You're completing the amino acid profile your mitochondria evolved expecting—the profile that comes from eating whole animals, nose-to-tail, the way humans did for millions of years.

Humans are water that's shaped by collagen and fat, then animated by protein and minerals. That's it!

That's the entire biological architecture in one sentence. 

Clean protein (muscle meat, whey, plant protein) gives you:

Essential amino acids for synthesis

BCAAs for mTOR signaling

But often insufficient glycine and proline

Collagen gives you:

Massive glycine (mitochondrial support)

Proline and hydroxyproline (structural repair)

The amino acid ratios your body uses to build 30% of its protein

You need both.

Not one or the other. Both.

Muscle meat for essential amino acids and mTOR signaling.
Collagen for glycine, mitochondrial function, and structural integrity.

The most important amino acids from the mitochondrial framework:

Glycine - heme, glutathione, structure

Cysteine - glutathione, iron-sulfur clusters

Methionine - methylation (but balance with glycine)

Lysine - collagen cross-linking, carnitine synthesis

BCAAs are useful but not foundational. Glycine is foundational.

Your mitochondria will prioritize making heme and glutathione over building muscle. If you're giving them leucine but not glycine, you're signaling "build" without providing the materials for the foundation.

This is why collagen works.

Not because it's magic. Because it provides what your mitochondria actually need, in the ratios they need it, for the functions they prioritize.

You are not just muscle.
You are connective tissue, gut lining, blood vessels, and bone—all held together by collagen.
And all of that is powered by mitochondria that require glycine to function.

Feed the ancient bacteria what they need, and they'll build you strong from the inside out.

That's the foundational framework of protein, now just enjoy the smoothie!