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Phosphatidic acid (PA) 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 bonded to the third carbon atom on the glycerol backbone. PA is a phospholipid typically embedded within the cell membrane, where it functions as a second messenger involved in many different cellular-signaling cascades.1 By way of its cellular signaling capacity, PA can elicit an anabolic response in muscle cells.

In fact, muscular contraction is thought to activate certain enzymes that biosynthesize PA in muscle cells, effectively increasing PA levels and activating mTOR-stimulated muscle protein synthesis, which promotes muscle growth. There have been several studies demonstrating this effect. One of these studies by Cleland et al.2 showed that electrically stimulated muscle contraction in rats led to a twofold increase in PA concentrations. While another investigation by O'Neill et al.3 demonstrated that elevations in PA occur in response to eccentric contractions, and this elevation in PA activated mTOR signaling for more than 12 hours.

Oral consumption of PA has also been shown to increase plasma concentrations of PA as rapidly as 30 minutes after consumption, with PA concentrations remaining elevated for as long as seven hours.4 Taken together, the elevation of PA in the body from oral supplementation, combined with its endogenous production from weight training, should result in greater muscle hypertrophy relative to resistance training alone.

PA Boosts Muscle Growth and Strength

Because of the potential of PA supplementation for muscle growth, several groups have investigated its muscle-building capacity. One seminal study by Hoffman et al.5 looked at the influence that soy-derived PA had on muscle growth and strength in 16 test subjects with significant weightlifting experience. The subjects were split into two groups, with one group receiving 750 milligrams of PA per day and the other group taking a placebo. During the experiment, each subject lifted weights four days a week at 70 percent of their one-repetition maximum (1RM) for all lifts during the entire eight-week trial period. Each subject was tested for strength and body composition at the end of the experimental period. The results showed that subjects ingesting PA demonstrated a 12.7 percent increase in squat strength and a 2.6 percent increase in muscle mass, while subjects consuming placebo showed only a 9.3 percent improvement in squat strength and a 0.1 percent change in muscle mass. Results from this study strongly indicate that PA ingestion combined with resistance training enhanced size and strength.

Soy-derived PA More Potently Drives Muscle Growth

While PA clearly plays a critical role in the stimulation of mTOR-driven muscle growth, different sources of PA, such as soy or egg, have a slightly different chemical makeup— with varying levels of unsaturated or saturated fatty acid chains at the first and second carbon positions within its glycerol backbone. This variation in chemical composition of PA could influence the impact on muscle growth— as it has been proposed that PA with one saturated and one unsaturated fatty acid, such as soy-derived PA, is more likely to promote cellular signaling events such as mTOR-activated muscle growth, relative to PA containing two saturated fatty acids as found in egg-derived PA, which is apparently more biochemically inert as a signaling compound.6

In order to screen for more efficient muscle-building forms of PA, a study by Joy et al.7 looked at the different impact of several kinds of phospholipids, including both egg and soy-derived PA, on muscle growth and strength. The study involved two independent experiments, where the first experiment looked at the ability of egg and soy-derived PA to activate mTOR in isolated muscle cells within a test tube (in vitro), and the second experiment measured muscle growth rates in humans consuming 750 milligrams of soy-derived PA while performing an eight-week, periodized weight-training program.

In the first experiment conducted by Joy et al., researchers found that out of all the phospholipids investigated, PA from soy triggered the largest increase in mTOR activity relative to all the other phospholipids, including egg-derived PA. The second experiment validated the findings from the first experiment, as soy-derived PA also produced a considerable increase in muscle mass of five pounds relative to the placebo group. This experiment also showed a statistically significant increase in leg press strength of 115 pounds within the PA-consuming group compared to the placebo group, which showed a smaller increase of only 50 pounds.

Taken together, this study effectively demonstrated that soy-derived PA more potently activates mTOR, improving muscle hypertrophy and maximal strength when combined with resistance training. This finding further supports the hypothesis that an unsaturated fatty chain found in soy-derived PA promotes superior gains in size and strength. Consequently, soy-derived PA appears to be the better source of PA relative to egg-derived PA, for enhancing the effects of resistance training on muscle mass and strength.

PA Prevents Muscle Breakdown

The ability of PA to stimulate muscle growth may also come from its recently discovered capacity to inhibit muscle protein breakdown, which ultimately leads to muscle hypertrophy— as decreased muscle protein breakdown tends to increase muscle protein levels, promoting muscle growth. The first indication that PA could inhibit muscle protein breakdown came from a study showing that increasing the amount of one of the enzymes that synthesizes PA in the body, PLD1, in isolated muscle cells increased PA levels. This increase in PA rapidly reduced expression of a set of genes that promote muscle protein breakdown.8 This study then went on to demonstrate that the same muscle-depleting genes could also be turned off by exposing these isolated muscle cells directly to PA.

Interestingly, some of the genes involved in the protein-degrading pathway that are turned off by PA can also be turned on by the extremely powerful muscle-depleting molecule myostatin, which suggests that PA may actually thwart some of the negative effects of myostatin on muscle growth.

Now, while these results are very intriguing, they certainly require additional experimentation, as the anti-catabolic effects of PA were only shown on muscle cells in vitro. Thus, more studies investigating the effects of PA in humans are required to fully confirm these findings.

In summary, all of the science indicates that PA increases muscle mass by activating the muscle-building enzyme mTOR, while potentially reducing muscle protein degradation. This prospective dual impact of PA on muscle protein levels is typically very advantageous for muscle growth— as it not only represents an effective way to trigger muscle protein synthesis, but also provides a way to mitigate the often underappreciated catabolic influence that intense weight training has on muscle tissue.

The positive influence of PA is even more pronounced when supplement use is optimally coordinated with weight-training sessions. So, the optimal supplementation protocol for PA should include at least 750 milligrams of soy-derived PA immediately after weightlifting, seeing that it is rapidly available within 30 minutes after oral ingestion and stays available for at least seven hours. Of course, this time frame of seven hours post-workout is when the catabolic effect from weight training is at or near its peak, and should be inhibited as quickly and strongly as possible to minimize any potential muscle loss, which will eventually provide superior gains in size and strength.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.