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.