Eight Weeks of Phosphatidic Acid Supplementation in Conjunction with Resistance Training Does Not Differentially Affect Body Composition and Muscle Strength in Resistance-Trained Men.

This study attempted to determine the effects of eight weeks of resistance training (RT) combined with phosphatidic acid (PA) supplementation at a dose of either 250 mg or 375 mg on body composition and muscle size and strength. Twenty-eight resistance-trained men were randomly assigned to ingest 375 mg [PA375 (n = 9)] or 250 mg [PA250 (n = 9)] of PA or 375 mg of placebo [PLC (n = 10)] daily for eight weeks with RT. Supplements were ingested 60 minutes prior to RT and in the morning on non-RT days. Participants’ body composition, muscle size, and lower-body muscle strength were determined before and after training/supplementation. Separate group x time ANOVAs for each criterion variable were used employing an alpha level of ≤ 0.05. Magnitude- based inferences were utilized to determine the likely or unlikely impact of PA on each criterion variable. A significant main effect for time was observed for improvements in total body mass (p = 0.003), lean mass (p = 0.008), rectus femoris cross-sectional area [RF CSA (p = 0.011)], and lower-body strength (p 0.05). Collectively, magnitude-based inferences determined both doses of PA to have a likely impact of increasing body mass (74.2%), lean mass (71.3%), RF CSA (92.2%), and very likely impact on increasing lower-body strength (98.1% beneficial). When combined with RT, it appears that PA has a more than likely impact on improving lower-body strength, whereas a likely impact exists for increasing muscle size and lean mass. Key points In response to eight weeks resistance training and PLC and PA (375 mg and 250 mg) supplementation, similar increases in lower-body muscle strength occurred in all three groups; however, the increases were not different between supplement groups. In response to eight weeks resistance training and PLC and PA (375 mg and 250 mg) supplementation, similar increases in lean mass occurred in all three groups; however, the increases were not different between supplement groups. In response to eight weeks resistance training and PLC and PA (375 mg and 250 mg) supplementation, similar increases in muscle mass (RF CSA) occurred in all three groups; however, the increases were not different between supplement groups. Supplementation of PA in conjunction with RT does not impose a differential benefit; however, regarding trends in the data magnitude-based inferences indicate that PA has a more than likely impact on improving lower-body strength, whereas a likely impact for increasing muscle mass when combined with resistance training. Key words: Phosphatidic acid, resistance training, body composition, muscle strength Introduction E Resistance training (RT) produces muscle hypertrophy due to the accretion of muscle protein over the course of the training period. The progressive accrual of myofibrillar protein is the net result of an overall increase in muscle protein synthesis (MPS) that occurs with each bout of resistance exercise. The process of MPS is governed by an integrated network of intracellular events that can be regulated by both systemic and local effects. Resistance exercise is known to induce systemic effects such as the release of hormones such as testosterone, growth hormone (GH), and insulin-like growth factor 1 (IGF-1) that can affect MPS by up-regulating intracellular signaling pathways. One such pathway involves the orchestration of phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), and mechanistic target of rapamycin (mTOR) and is known as the PI3K/Akt-mTOR pathway. This intracellular signaling pathway has been recognized as a stimulus for skeletal muscle protein synthesis (MPS), and the cumulative effects of increased MPS over time can lead to muscular hypertrophic adaptations (Bodine et al., 2001; Koopman et al., 2006; Sandri et al., 2008). Activity of the PI3K/Akt-mTOR pathway has been shown to be sensitive to various substances such as L-leucine (Dennis et al., 2011), ursolic acid (Ogasawara et al., 2013), and phosphatidic acid (PA) (Joy et al., 2014). Regarding PA, it is an acid form of phosphatidate, a part of common phospholipids which are major components of cell membranes. PA is a simplistic form of diacyl-glycerophospholipids, and is a vital cell lipid acting as a biosynthetic precursor for the materialization (directly or indirectly) of all acylglycerol lipids in the cell (Foster et al. 2014). PA is formed from the hydrolysis of phosphatidylcholine by the enzyme, phospholipase-D (PLD). PLD is a prime regulator in the activation of mTOR signaling by a variety of stimuli (Yoon et al., 2015). PA binding to mTOR consequently results in the stimulation of mTORC1 kinase activity and exogenous PA has been shown to directly activate mTORC1 signaling, possibly due to its association with the FKBP12-rapamycin-binding (FRB) binding domain of mTOR (Joy et al., 2014). An additional stimuli for mTOR up-regulation is muscle contractions which are associated with damage to the sarcolemma resulting in phospholipase D (PLD) to be dislodged from the z-line of muscle tissue and hydrolyzes phosphatidylcholine to yield PA, a lipid second messenger, and choline (Yamada et al., 2012). More specifically, eccentric contractions have demonstrated the ability to result in a significant elevation of intracellular PA which inhibited the synthesis of PA by PLD and blocked the eccentric contraction-induced increase in S6K1 phosphorylation (O’Neil et al., 2009). Yoon et al. (2015) provided evidence that the mTOR inhibitor domain-containing mTOR-interacting protein (DEPTOR) is displaced from mTORC1 by PA when generated by PLD. This leads to activation of mTORC1 and when taken together, this data provides indication that the increase in PA promotes the plausible activation of mTOR signaling. Potentially, the combination of resistance training (RT) with exogenous PA supplementation could further stimulate an up-regulation of mTOR, thereby augmenting increases in MPS. Although, to date there are no known published studies examining the effectiveness of PA supplementation and RT on mTORC1 activity in human skeletal muscle. However, there are three known studies investigating PA supplementation (750 mg daily) in combination with RT and the subsequent effects on body composition and muscle mass and strength in humans (Escalante et al., 2016; Hoffman et al., 2012; Joy et al., 2014). As with many studies, however, discrepancies exist in various aspects of these three investigations and can likely be attributed to such issues as differences in the experimental designs of the studies such as RT program structure and RT session supervision, to name a few. In regards to lean mass, muscle cross sectional area (CSA), and strength, Hoffman found only significant increases with RT whereas Joy et al. (2014) and Escalante et al. (2016) founds significant increase with RT that were a result of daily PA supplementation. Interestingly, Escalante et al. (2016) found the most robust impact on strength and lean body mass improvements utilizing a similar design to the study of Joy et al. (2014), but in addition to 750 mg PA the supplement included L-leucine, HMB, and vitamin D which make it difficult to clearly discern if these results were primarily attributable to PA. The purpose of this study was to compare the effects of an eight week resistance training (RT) program in conjunction with daily, orally-delivered PA supplementation on body composition and muscle mass and strength at doses of 375 mg and 250 mg, compared to placebo.