Phosphatidic acid is a phospholipid that DIRECTLY activates mTOR — the master regulator of muscle protein synthesis. This isn't through any indirect mechanism: PA binds to the FRB domain of mTOR with high affinity, essentially mimicking the signal that mechanical loading (lifting weights) sends to build muscle. A 2014 study found 750mg/day PA increased lean body mass by 2.4 kg and strength compared to placebo over 8 weeks of resistance training. The mechanism is mechanistically validated (Hornberger lab at UW-Madison) and the supplement form (Mediator® PA) has multiple positive human trials.
Phosphatidic acid is a signaling lipid produced in muscle cells during resistance training: (1) Mechanical loading activates phospholipase D (PLD) in the muscle cell membrane; (2) PLD cleaves phosphatidylcholine → phosphatidic acid; (3) PA binds directly to the FRB domain of mTORC1 (the same binding site where rapamycin inhibits mTOR); (4) PA binding activates mTORC1 → phosphorylates p70S6K and 4E-BP1 → initiates muscle protein synthesis. Supplemental PA augments this endogenous signal — essentially giving the mTOR pathway MORE activation signal than training alone would produce. This is independent of the insulin/Akt pathway, providing a separate input to mTOR.
Reviewed by the Scan Dose Research Team and Clinical Advisory Board | Last updated:
Not medical advice. Based on published clinical research and systematic reviews.