Increase your muscle growth with phosphatidic acid

All scientific research indicates that phosphatidic acid increases muscle mass via activation of the muscle-building enzyme mTOR, while potentially reducing the breakdown of muscle protein.

Phosphatidic acid is a compound consisting of a glycerol backbone with two fatty acid chains linked to the first and second carbon atoms and a phosphate group linked to the third carbon atom of the glycerol backbone. Phosphatidic acid is a phospholipid typically found in the cell membrane, where it acts as a secondary messenger involved in many different cellular signaling cascades (1). Through this cellular signaling capacity, phosphatidic acid can induce an anabolic response in muscle cells.

Indeed, muscle contractions are believed to activate certain enzymes that cause biosynthesis of phosphatidic acid in muscle cells, thereby increasing phosphatidic acid levels and activation of mTOR-stimulated protein synthesis, which promotes muscle growth. One of the studies by Cleland and colleagues (2) showed that electrically stimulated muscle contractions in rats led to a doubling of phosphatidic acid concentrations. Other studies by O'Neil and colleagues (3) showed that increases in phosphatidic acid concentrations occur in response to eccentric contractions and that these increases in phosphatidic acid levels enhanced mTOR signaling for more than 12 hours.

Oral ingestion of phosphatidic acid has been shown to increase phosphatidic acid plasma concentrations as early as 30 minutes after ingestion, and phosphatidic acid concentrations remained elevated for up to seven hours (4). In combination, the increase in phosphatidic acid levels in the body from oral supplementation combined with endogenous production from weight training should result in greater muscle hypertrophy compared to resistance training alone.

Phosphatidic acid increases muscle growth and strength

Due to the potential of phosphatidic acid supplementation for muscle growth, several groups have investigated its muscle-building capacity. A groundbreaking study by Hoffman and colleagues (5) examined the effect of soy-derived phosphatidic acid on muscle growth and strength in 16 subjects with significant weight training experience. The subjects were divided into two groups, one of which consumed 750 mg of phosphatidic acid per day, while the other received only a placebo. During the experiment, all subjects trained with weights four times a week, using 70 percent of their maximum weight for one repetition (1RM) for all exercises throughout the eight-week study period.

At the end of the study, strength and body composition were examined in all subjects. The results showed that subjects who had used phosphatidic acid had a 12.7 percent increase in squat strength and a 2.6 percent increase in muscle mass, while subjects who had taken a placebo only increased their squat strength by 9.3 percent and their muscle mass by 0.1 percent. The results of this study strongly suggest that taking phosphatidic acid in combination with resistance training increased muscle mass and strength.

Soy-derived phosphatidic acid drives muscle growth

While phosphatidic acid clearly plays a critical role in stimulating mTOR-driven muscle growth, different sources of phosphatidic acid, such as soy or eggs, have slightly different chemical compositions, with varying levels of unsaturated or saturated fatty acid chains at the first and second carbon positions of the glycerol backbone. These variations in the chemical composition of phosphatidic acid could influence the impact on muscle growth. Phosphatidic acids containing one saturated and one unsaturated fatty acid, such as soy-derived phosphatidic acid, are believed to be more likely to promote cellular signaling events such as mTOR-activated muscle growth than phosphatidic acids containing two saturated fatty acids, such as egg-derived phosphatidic acid, which appear to be less biochemically active as a signaling compound (6).

To search for more efficient muscle-building forms of phosphatidic acid, a study by Joy and colleagues (7) investigated the differential impact of different types of phospholipids, including soy- and egg-derived phosphatidic acid, on muscle growth and strength. The study involved two independent experiments, the first of which examined the ability of soy- and egg-derived phosphatidic acid to activate mTOR in isolated muscle cells in vitro, and the second of which measured muscle growth rates in humans who ingested 750 mg of soy-derived phosphatidic acid daily while completing an eight-week periodized weight training program.

In the first experiment conducted by Joy and colleagues, the scientists found that of all the phospholipids studied, soy-derived phosphatidic acid produced the greatest increase in mTOR activity relative to the other phospholipids, including egg-derived phosphatidic acid. The second experiment confirmed the results of the first experiment, as soy-derived phosphatidic acid also produced a significant increase in muscle mass of 5 pounds relative to the placebo group. This experiment also showed a statistically significant increase in leg press strength of 115 pounds in the group taking phosphatidic acid, while members of the placebo group only increased their strength by 50 pounds.

Taken together, this study effectively shows that soy-derived phosphatidic acid activates mTOR more strongly and increases muscle mass and maximum strength when combined with resistance training. These results support the hypothesis that an unsaturated fatty acid found in soy-derived phosphatidic acid promotes superior gains in mass and strength. Thus, soy-derived phosphatidic acid appears to be the superior source of phosphatidic acid compared to egg-derived phosphatidic acid when it comes to increasing the effects of resistance training on muscle mass and strength.

Phosphatidic acid prevents muscle breakdown

Phosphatidic acid's ability to stimulate muscle growth may also be related to its recently discovered capacity to inhibit muscle breakdown, which ultimately leads to hypertrophy, as reduced muscle protein breakdown tends to increase muscle protein levels, thereby promoting muscle growth.

The first indication that phosphatidic acid could inhibit muscle protein breakdown came from a study that showed that increasing the amount of one of the enzymes that synthesizes phosphatidic acid in the body - PDL1 - in isolated muscle cells increased phosphatidic acid levels. This increase in phosphatidic acid levels rapidly reduced the expression of a number of genes that promote muscle protein degradation. (8) This study further showed that the same muscle-degrading genes were also silenced when the muscle cells were directly exposed to phosphatidic acid.

Interestingly, some of the genes involved in the protein-degrading pathway that are turned off by phosphatidic acid can be activated by the extremely potent muscle-degrading molecule myostatin, suggesting that phosphatidic acid may prevent some of the negative effects of myostatin on muscle growth.

Although these results are very intriguing, further research is certainly needed as the anti-catabolic effects of phosphatidic acid have so far only been demonstrated in vitro on muscle cells. Thus, further studies investigating the effects of phosphatidic acid in humans need to be carried out to fully confirm these results.

In summary, all of this scientific evidence suggests that phosphatidic acid increases muscle mass via activation of the muscle-building enzyme mTOR, while potentially reducing muscle protein breakdown. Such a likely dual effect as that of phosphatidic acid on muscle protein levels is typically very beneficial for muscle growth, as it not only provides an effective way to stimulate protein synthesis, but also provides a way to mitigate the often underestimated catabolic effect that intense weight training has on muscle tissue.

The positive influence of phosphatidic acid is even more pronounced when this supplement is used in optimal coordination with weight training sessions. The optimal supplement protocol for phosphatidic acid should include at least 750 mg of soy-derived phosphatidic acid taken immediately after exercise, as phosphatidic acid is available to the body within 30 minutes of oral ingestion and remains available for at least seven hours. This seven-hour post-workout window is, of course, the period during which the catabolic effects of training with weights are near their maximum and should be inhibited as quickly and strongly as possible to prevent potential muscle breakdown, which will ultimately lead to superior gains in muscle mass and strength.

References:

1. Wang X, Devaiah SP, et al. Signaling functions of phosphatidic acid. Prog Lipid Res 2006; 45, 250-278.
2. Cleland PJ, Appleby GJ, et al. Exercise induced translocation of protein kinase C and production of diacylglycerol and phosphatidic acid in rat skeletal muscle in vivo. Relationship to changes in glucose transport. J Biol Chem 1989: 246, 17704-17711.
3. O'Neil TK, duffy LR, et al. The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions. J Physiol 2009; 587, 3691-3701
4. Purpura M, Jager R, et al. Effect of oral administration of soy-derived phosphatidic acid on concentrations of phosphatidic acid and lyso-phosphatidic acid molecular species in human plasma. J Int Sports nutr 2013; 10, 22
5. Hoffman JR, Stout JR, et al. Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men. J Int Soc Sports Nutr 2012; 9, 47
6. Foster DA. Regulation of mTOR by phosphatidic acid? Cancer Res 2007; 67, 1-4
7. Joy JM, Gundermann DM, et al. Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy. Nutr Metab (Lond) 2014; 11, 29
8. Jaafar R, De Larichaudy J, et al. Phospholipase D regulates the size of skeletal muscle cells through the activation of mTOR signaling. Cell Commun Signal 2013; 11, 55

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