Increase Strength Muscle Gain Phosphatidic acid

Phosphatidic acid may increase muscle mass and strength

Aesthetic Physique Andrej Rantasa

Phosphatidic acid has only recently been identified as an important signaling molecule in both plants and animals. Phosphatidic acid is a key intermediate in lipid metabolism [1]. It is a constituent of all cell membranes and also acts as an intermediate in the biosynthesis of triacylglycerols and other phospholipids [2]. This acid is especially interesting as it has been shown to activate the mammalian target of rapamycin (mTOR) [3].

mTOR Pathway Stimulation by Phosphatidic Acid

The mammalian target of rapamycin (mTOR) governs all cell growth and cell reproduction. In adult skeletal muscle the mTOR signaling pathway is currently recognized as the major pathway regulating protein synthesis leading to increased rate of mRNA translation into proteins within cells [4]. In a study by Fang et al. [3] phosphatidic acid has been identified as a critical component of mTOR signaling. Both nutritional and mechanical stimuli have been implicated in stimulating this pathway. It has been shown that mechanical activation of mTOR signaling via resistance training may be further enhanced with the presence of phosphatidic acid [5] by increased S6 kinase activity [6,7]. So, unlike resistance exercise with eccentric contractions, phosphatidic acid activates mTOR signaling through a PI3K–PKB-independent mechanism [8].

Effects of Phosphatidic Acid Ingestion on Lean Body Mass and Strength

Besides its ability to activate mTOR signaling pathway, phosphatidic acid is also thought to enhance the anabolic effects of resistance training. Hoffman and associates [2] conducted a pilot study on 16 bodybuilders who were randomly assigned to either ingest 750 mg of phosphatidic acid or a placebo. Subjects that received phosphatidic acid demonstrated greater increase in squat strength and lean body mass but didn’t reach statistical significance. In a follow-up study [9] in 28 bodybuilders, 750 mg of phosphatidic acid significantly improved responses in skeletal muscle hypertrophy, lean body mass, and maximal strength.

These studies were funded by Chemi Nutra, a patent holder of soy-derived phosphatidic acid also known as Mediator®.


Typical dose used in clinical studies is 750 mg per day.

Side Effects of Phosphatidic Acid

Phosphatidic acid seems to be very well tolerated and no adverse events have been reported [2].


  1. Athenstaedt, Karin, and Günther Daum. “Phosphatidic acid, a key intermediate in lipid metabolism.” European journal of biochemistry 266.1 (1999): 1-16.
  2. Hoffman, Jay R., et al. “Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men.” Journal of the International Society of Sports Nutrition 9.1 (2012): 47.
  3. Fang, Yimin, et al. “Phosphatidic acid-mediated mitogenic activation of mTOR signaling.” Science 294.5548 (2001): 1942-1945.
  4. McCarthy, John J., and Karyn A. Esser. “Anabolic and catabolic pathways regulating skeletal muscle mass.” Current opinion in clinical nutrition and metabolic care 13.3 (2010): 230.
  5. Hornberger, T. A., et al. “The role of phospholipase D and phosphatidic acid in the mechanical activation of mTOR signaling in skeletal muscle.” Proceedings of the National Academy of Sciences of the United States of America 103.12 (2006): 4741-4746.
  6. Lim, Hyung-Kyu, et al. “Phosphatidic acid regulates systemic inflammatory responses by modulating the Akt-mammalian target of rapamycin-p70 S6 kinase 1 pathway.” Journal of Biological Chemistry 278.46 (2003): 45117-45127.
  7. Xu, Yong, et al. “Activation of mTOR signaling by novel fluoromethylene phosphonate analogues of phosphatidic acid.” Bioorganic & medicinal chemistry letters 14.6 (2004): 1461-1464.
  8. O’Neil, Tyriina K., et al. “The role of phosphoinositide 3‐kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions.” The Journal of physiology 587.14 (2009): 3691-3701.
  9. Joy, Jordan M., et al. “Phosphatidic acid supplementation increases skeletal muscle hypertrophy and strength.” Journal of the International Society of Sports Nutrition 10.Suppl 1 (2013): P13.

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