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.

Thiamine/B1 is prob the best single example of why micronutrient maxxing matters at a systems level (if you are gonna read this, then read the whole thing) B1 is a cofactor for pyruvate dehydrogenase. PDH converts pyruvate → acetyl-CoA. This is THE gateway reaction between glycolysis and the Krebs cycle. Without adequate B1, this step bottlenecks. Pyruvate backs up, gets shunted to lactate instead. You can see this happen on Metabolomix+/OAT testing or just measuring finger-prick lactate. No acetyl-CoA = no NADH/FADH2 feeding the ETC = ↓ ATP across every cell. You can eat plenty of glucose and still not be able to turn it into usable energy which is when people run into issues with eating high carb. BUT B1 does way more than just energy. PDH also produces acetyl-CoA for acetylcholine synthesis. ↓ B1 → ↓ ACh → impaired vagal tone → ↓ gut motility, ↓ HCl secretion, ↓ bile flow, ↓ heart rate variability, ↓ parasympathetic tone overall. This is one of the core drivers of a lot of people's gut issues btw. It is why B1 deficiency can present as POTS-like symptoms, gastroparesis, chronic constipation, weird heart rate issues. And then you have transketolase enzyme in the pentose phosphate pathway which also needs B1. This pathway produces NADPH (key for antioxidant defence, glutathione recycling, fatty acid synthesis etc) and ribose-5-phosphate for DNA/RNA synthesis and repair. Branched-chain alpha-ketoacid dehydrogenase (another enzyme) is also B1 dependent. This enzyme catabolizes branched chain amino acids. ↓ B1 → ↑ BCAA accumulation. Also something you can sometimes pick up on metabolomix+ testing altough arguably NutrEval is a lot better for this. So from ONE micronutrient deficiency you get a whole bunch of shit going wrong: - ↓ ATP production - ↓ Acetylcholine → autonomic dysfunction - ↓ Gut motility and full digestive cascade - ↓ Antioxidant capacity (NADPH) - ↓ DNA repair substrate - ↑ Lactate (exercise intolerance, muscle pain) - ↑ Dysfunctional BCAA and amino acid metabolism Youend up with fatigue, brain fog, poor digestion, slow motility, exercise intolerance, and autonomic dysfunction. Maybe in the centralized system you get 5 different diagnoses and 5 different specialists, and a dozen drugs. No bueno. B1 demand scales with carb intake btw. Higher carb = more pyruvate = more PDH activity needed = more B1 required. High calorie modern diets with refined carbs are essentially increasing B1 demand while providing almost none of it - this is what Dr Lonsdale figured out! Alcohol does the same as it inhibits B1 absorption and ↑ urinary excretion. This is what systems biology looks like at the micronutrient level. One cofactor touching everything.

People take NAC long term for biofilms and don't realize its degrading their gut mucus layer at the same time. NAC is a mucolytic and it breaks disulfide bonds. Biofilm matrix uses disulfide bonds but so does MUC2 mucin (your protective gut mucus) so its something to be aware and careful of. Its a problem because your butyrate producers live IN that mucus layer.

How many people with auto-immune thyroid disease have inflamed & hyper-permeable guts? A lot.

Client message this morning (love getting these): "Googely moogely I feel strong on carbs, workouts are way easier" "Feels like a huge achievement, I never thought I was going to be able to kick the habit" (chronic addiction to caffeine) Maybe, just maybe, when you.... Resolve SIBO/over-fermentation → micronutrient replete →restore metabolic pathways (TTFD maxing) → layer on carbs → you can access a degree of energy not experienced by most these days. It was important to address his gut health first because carbs were being fermented in his small intestine, not absorbed and oxidised. Gas, bloating, malabsorption. Motility was a big issue for him. B1, B2, B3, Mg, zinc, trace minerals. All functionally depleted cus of poor absorption and ↑ metabolic demand from chronic inflammation. So this step was taken alongside/part of gut health optimization. Thiamine is the rate limiting cofactor for PDH and alpha-KGDH. Without it, pyruvate backs up, Krebs cycle stalls, you're running on partial glucose oxidation and stimulants to feel functional. Now with gut health fixed, magnesium + B1 repleted he is able to properly add carbs back into his life and he is in a position where quitting crutch of chronic caffeine addiction is actually possible. Super proud of him!🙏

Side-quest maxxing is pro health

Lets talk about the migrating motor complex (MMC) today. Your gut has a built-in cleaning system - it is key to optimizing gut health It's essentially a cyclical wave of contractions that sweeps through your stomach and small intestine every 90-120 minutes during the fasted state. Its job is to clear residual food particles, dead cells, mucus, and bacteria from the upper gut and push them toward the colon. This is how the small intestine maintains low bacterial density (music to the ears of those with SIBO/SIFO). When the MMC works, bacteria stay where they belong. When it doesn't, they accumulate and you get a bunch of downstream issues. The MMC has three phases. Phase I - Rest. Minimal contractions. The smooth muscle resets. Phase II - Irregular contractions building in intensity. Preparing for clearance. Phase III - High-amplitude rhythmic peristaltic contractions that sweep everything forward. This is the housekeeping wave. Phase III is initiated by motilin, a peptide hormone released during fasting (STOP GRAZING). Vagal tone and enteric nervous system integrity are required for proper coordination as well - B1, B5, choline, B6 are all key. But really what I want to focus on is this very simple practical fact that the body building community especially doesn't seem to realise. Eating shuts it off. Even small caloric inputs, especially carbs or protein, immediately suppress the MMC and switch the gut into fed-state segmentation contractions optimized for digestion. Every time you snack, the cleaning cycle resets. So if you're grazing all day, the MMC never completes. Bacteria aren't cleared = They migrate upward = SIBO develops. This is also why impaired MMC function shows up as more than just bloating. Constipation, acid reflux, bile reflux, that heavy fullness sensation after eating (which is abdominal distension, not gas production). Things that disrupt the MMC: - Frequent snacking/grazing - Chronic stress (↓ vagal tone) - Opioids (got some clients who developed SIBO from this most likely) - Anticholinergics - Post-infectious enteric nerve damage (you can test for this btw - anti-vinculin antibodies. - Circadian disruption. Things that support it - Consistent meal timing - Adequate fasting windows between meals (3-4+ hours) - Intact cholinergic signalling - Proper sleep-wake rhythms - Ginger maxxing

Anyone else feel like they have infinite energy running bare-chest, bare-foot on the beach by the water's edge? Is this the way?

Gm, dont let rain/clouds stop you from going out for sunrise

If you wanna get sick as fast as possible, alter your sleep schedule by +/- 3hrs for 3 consecutive nights and understand the importance of circadian biology in the meantime

Raw egg yolks can single handedly solve certain gut issues related to PC deficiency and poor bile metabolism