Gm

There are no words

Magical things happen when you replete all micronutrient and microwavelength deficiencies.

Bottlenecks get resolved, optimal pathways are liberated and the flux of vitality that modernity and its environmental mismatches stole from you starts to flow once again.

As you get older there is a progressive micronutrient malabsorption issue creating downstream dysfunction.

All of teh systems responsible for absorbing those micronutrients deteriorate with age.

Stomach acid declines (↓ HCl → ↓ B12, iron, zinc, magnesium liberation from food).

Parietal cells atrophy → intrinsic factor drops → B12 absorption tanks.

Bile production slows → fat-soluble vitamins (A, D, E, K2) aren't absorbed properly.

Pancreatic enzyme output drops → protein-bound minerals stay bound.

But the energy side is also really interesting to me becauase nutrient absorption is an active process.

Your enterocytes need ATP to run transport proteins like DMT1 for iron, calbindin-dependent transport for calcium, sodium-dependent carriers for B vitamins.

As mitochondrial function declines with age (heteroplasmy accumulation, ↓ ETC efficiency), even with "adequate" intake your gut cells can't physically grab the nutrients.

↓ mito function → ↓ absorption → ↓ cofactors (B2, B3, CoQ10, iron, copper) → ↓ mito function further.

Probably this explains a lot of the "unexplained" deterioration people experience after 50.

So functional testing becomes WAY more important as you age.

Metabolomix+, comprehensive bloods, functional markers like methylmalonic acid for B12 status. And delivery route matters too in many cases. Sublingual B12 might bypass the intrinsic factor problem. Dermal magnesium bypasses the gut.

Interesting stuff to keep into account.

Pull-up day nonetheless

Over a third of commonly prescribed drugs are known mitotoxins. Statins, PPIs, certain antibiotics, metformin, fluoroquinolones, etc...

They impair electron transport, uncouple membranes, or deplete cofactors like CoQ10.

So you show up with fatigue, muscle pain, brain fog but nobody connects it to the prescription. You end up gettng more drugs for those symptoms = another vicious cycle.

I also believe the real number is prob higher than a third btw. Most drugs just haven't been tested for mitotoxicity. But is what it is.

This is a great website for checking the mitochondrial effects of drugs btw:
mitotox.org

Butyrate is the primary fuel source for colonocytes (not glucose).

If you lose your butyrate producers (faecalibacterium, roseburia) → colonocytes lose their preferred fuel → ↓ mito function → ↓ decreased oxygen utilization → ↑ luminal oxygen → obligate anaerobes die off & facultative anaerobes like e. coli expand = dysbiosis

BUT those were the bacteria making the butyrate in the first place so its actually a vicious cycle once this self-regulating system loses its tensegrity.

So in order to fix the microbiome you gotta fix colonocyte energy production and O2 utilization.

The centralized system leads to hyperspecialization. Heart, gut, hormones, brain. Each specialist looking at their niche in isolation, as if all these organ systems are independent of each other.

If someone shows up with fatigue, bloating, brain fog, and weird hormone numbers. They get referred to 4 specialists, get 4 separate workups, prob end up on a cocktail of prescriptions. But is there actually anyone asking how these pieces might fit together?

BUT they always fit together (to some extent).

Chronic sympathetic overdrive → impairs thyroid hormone conversion = subclinical hypothyroidism

Chronic sympathetic overdrive → high blood pressure & metabolic syndrome.

That same sympathetic dominance → ↓ vagal tone → ↓ gut motility, ↓ HCl, ↓ bile output → food sits, bacteria overgrow = IBS.

Magnesium & B6 depletion → ↓ GABA synthesis → anxiety, poor sleep.

But what could have triggered that chronic sympathetic overdrive? And what could be keeping it in place, even after that trigger is no longer there? Likely a collection of interacting factors.

That is why I love systems biology because it attempts to create a working model of everything that is going on. Understanding is always limited, so must be built with humility and be responsive to new data or falsified hypothesis. But you have to at least try to connect the dots.

This is what decentralized health optimization is about.

Your gut has its own local clock genes (PER, CRY, BMAL1). These regulate enzyme secretion, motility, barrier permeability on a 24h cycle.

Eating late at night when these clocks are in rest phase → ↓ digestive enzyme output → ↓ motility → food sits longer → more fermentation → bloating.

WHAT you eat matters. (of course it does). But WHEN you eat also matters cus your gut literally processes food differently depending on time of day (and personal consistency is key here as well).

CoQ10 is fascinating to me. It does two things in the inner mitochondrial membrane which are crucial.

1. Shuttles electrons from Complex I/II → III (relating to energy production)
2. Lipid-soluble antioxidant sitting right where ROS are generated

↓ CoQ10 = ↓ ATP AND ↑ oxidative damage to cardiolipin and mtDNA simultaneously = so you get increased heteroplasmy rate

EAT MORE HEART.

Then you have one of the most widely distributed drugs in the world, statin, which inhibit HMG-CoA reductase. That is thesame pathway that produces CoQ10. I also believe research underestimates statin-induced fatigue and muscle issues, but is what it is.

SIBO keeps coming back for a lot of people cus they only address the overgrowth, not the motility.

The migrating motor complex sweeps bacteria out of the small intestine between meals. Only runs in fasted state.

What impairs MMC:
- ↓ vagal tone (stress, B1, B5, choline deficiency)
- Constant snacking (MMC needs fasting to activate)
- Hypothyroidism (low motilin receptor sensitivity)
- Post-infectious nerve damage (vinculin/CdtB antibodies - this will actually lead to long term issues unfortunately)

In fact, most people should optimize motility before touching antimicrobials, sometimes they aren't even needed.

Cool place to work. Green Nature + NIR light.