What is behind Energy & Fatigue
The gap between what you intend and what your body will fund. Distinct from sleepiness — you can be exhausted and wide awake — and it splits into a peripheral limb (the muscle) and a central limb (the drive), which respond to different things. Evidence A — Human trial evidence.
The cell's master energy sensor — when fuel runs low it ignites fat-burning, glucose uptake and mitochondrial renewal while standing down growth. Evidence A — Human trial evidence.
PGC-1α — the master regulator of mitochondrial biogenesis, building new cellular powerplants and oxidative endurance. Evidence A — Human trial evidence.
Mitochondrial energy (ATP) output. Evidence A — Human trial evidence.
The transcription factor that commands the body's own antioxidant and detoxification arsenal. Evidence A — Human trial evidence.
The hypothalamic–pituitary–adrenal axis and its hormone cortisol — the body's central stress-and-recovery command. Evidence A — Human trial evidence.
The cell's self-cleaning and recycling program — it digests worn proteins and organelles and renews the interior. Evidence A — Human trial evidence.
A sensor of cellular stress that ignites inflammation driven by damage rather than by germs. Evidence A — Human trial evidence.
Evidence on these pathways
AMPK → Insulin Sensitivity. “In model systems, sustained decreases in AMPK activity accompany IR, whereas AMPK activation increases insulin sensitivity.” — AMPK, insulin resistance, and the metabolic syndrome. The Journal of Clinical Investigation, 2013, volume 123, issue 7, pages 2764-2772. doi:10.1172/JCI67227
Autophagy → Proteostasis. “We show that HPK-1 fortifies proteostasis and extends longevity by an additional independent mechanism: induction of autophagy.” — The homeodomain-interacting protein kinase HPK-1 preserves protein homeostasis and longevity through master regulatory control of the HSF-1 chaperone network and TORC1-restricted autophagy in Caenorhabditis elegans. PLoS Genetics; 2017; volume 13; page/elocation not printed on either retrieved record. doi:10.1371/journal.pgen.1007038
HPA Axis / Cortisol → Cognition. “Whereas treatments used in previous studies generally affect more than one memory phase and therefore cannot detect possible differential effects of glucocorticoids on the distinct phases of acquisition, consolidation and retrieval, here we show that treatment of healthy humans with cortisone at acute-stress levels specifically impaired retrieval of declarative long-term memory for a word list.” — Acute cortisone administration impairs retrieval of long-term declarative memory in humans. Nature Neuroscience, 2000, vol 3, pp 313-314. doi:10.1038/73873
HPA Axis / Cortisol → Digestive Function. “Reports have consistently established that central administration of CRF acts in the brain to inhibit gastric emptying while stimulating colonic motor function through modulation of the vagal and sacral parasympathetic outflow in rodents.” — Corticotropin-Releasing Factor and the Brain-Gut Motor Response to Stress. Canadian Journal of Gastroenterology, 1999, vol 13, pp 18A-25A. doi:10.1155/1999/375916
Formulas that act on these pathways
Acts on 6 of these pathways: Fatigue, AMPK, PGC-1α Biogenesis, Nrf2, HPA Axis / Cortisol, Autophagy.
Acts on 5 of these pathways: AMPK, PGC-1α Biogenesis, Nrf2, HPA Axis / Cortisol, Autophagy.
Acts on 5 of these pathways: AMPK, PGC-1α Biogenesis, Nrf2, HPA Axis / Cortisol, Autophagy.
Acts on 5 of these pathways: Fatigue, AMPK, PGC-1α Biogenesis, Nrf2, HPA Axis / Cortisol.
Acts on 4 of these pathways: AMPK, PGC-1α Biogenesis, Nrf2, Autophagy.
Acts on 4 of these pathways: AMPK, PGC-1α Biogenesis, Nrf2, Autophagy.
What this page does not claim
This page names the pathways involved and the published evidence on each. It does not claim that any formula treats, cures or prevents Energy & Fatigue. A pathway opens here only on graded, published evidence, under a standard fixed before the evidence was gathered, and every figure above carries its grade.
These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.