The primary purpose of this study was to investigate the effects of 8 weeks of a MIPS in resistance-trained individuals during a periodized resistance training program on skeletal muscle hypertrophy, lean body mass, and strength relative to a placebo matched control. The primary findings of this research were in congruence with our hypotheses that Xpand® 2X supplementation can improve adaptations in skeletal muscle hypertrophy, LBM, and strength.

Skeletal muscle hypertrophy and lean body mass

This MIPS contains a proprietary blend of ingredients reported previously to augment the accretion of skeletal muscle. For example, creatine monohydrate has been reported as the most effective ergogenic aid currently available regarding LBM and high-intensity exercise capacity, particularly in untrained individuals[14]. Creatine and its various forms have been thoroughly researched, yet to date no study has shown any form of creatine to be superior to creatine monohydrate, which was used in this study (23, 33). Supplementation with creatine can increase total resistance training volume via ATP re-synthesis[14], and total training volume has been closely linked with skeletal muscle accretion. Additionally, creatine supplementation has been demonstrated to increase the activation of satellite cells and myonuclei in muscle following chronic resistance training[15]. Moreover it is conceivable that the osmotic pressure created by creatine that increases the hydration status of cells, resulting in potentially hypertrophic effects[16]. This mechanism of action is what causes creatine to increase strength, but can benefit almost every body system, including the brain, bones, muscles, and liver[17]. Lastly, long term studies have observed that those supplementing with creatine experience 200% increases in LBM compared to placebo[14].

Branched chain amino acids have previously been shown as efficacious in the accretion of skeletal muscle mass[2]. One BCAA of particular interest is leucine, which has been shown to increase muscle protein synthesis (MPS) without the presence of the other essential amino acids[18] Additionally, Karlsson et al.[19] found that supplementation with BCAAs during resistance exercise results in greater phosphorylation of ribosomal S6 kinase, a rate limiting enzyme in the signaling network responsible for regulation of protein synthesis in skeletal muscles. Moreover, BCAAs seem to decrease soreness after eccentric exercise[20] and, they prevent declines in both testosterone and power following an overreaching cycle[21].

Beta-Alanine supplementation has consistently been demonstrated to augment muscle carnosine concentrations in humans[22–25]. Harris et al.[22] concluded that carnosine plays an essential role as an intracellular buffer within the skeletal muscle of humans. More importantly, beta-alanine supplementation has been shown to enhance physical performance during high intensity exercise bouts while also delaying the onset of neuromuscular fatigue[26].

Agmatine is a derivative of the amino acid arginine. Agmatine has been studied for its impact on nitric oxide, wellbeing, and hormone status[27, 28]. Agmatine has been noted to support nitric oxide (NO) production via stimulation of endothelial nitric oxide synthase (eNOS).[29–31]. This process is essential for the proper functioning of the polyamine biosynthetic pathways to occur[29–31]. The body’s organs require polyamines for their growth, renewal, and metabolism. Polyamines also have a profound stabilizing effect on a cell DNA and are essential to the healthy function of the nervous system[29, 30]. Therefore, these pathways, although not fully elucidated, play an important role in normal cell homeostasis.

Lastly, Creatinol-O-Phosphate (COP) is known primarily for its abilities as an intracellular buffer. Creatinol-O-Phosphate has been shown to assist in stabilizing intracellular and extracellular pH levels, ultimately prolonging anaerobic glycolysis in the presence of lactic acid[7]. Creatinol-O-Phosphate has also been shown to activate satellite cells in skeletal muscle, theoretically increasing their capacity for muscle growth[7]. To date this is the first study that we are aware of to analyze this specific combination of ingredients.

Strength

Strength is one of the most critical attributes underlying success in sport[32]. The collective results of the present study suggest that bench press strength following Xpand® 2X supplementation are optimized within the context of a periodized training split. Most of the individual ingredients found within the pre-workout matrix have been demonstrated to individually enhance a variety of strength measures. For example, creatine monohydrate has repeatedly been shown to augment strength[33]. In addition to creatine, this MIPS contains a number of nootropics including glucuronolactone, caffeine, and taurine, which can possibly decrease perceived exertion and augment intra-workout performance. For example, caffeine has been demonstrated to enhance strength acutely through an adenosine receptor antagonist mediated mechanism and subsequent central nervous system stimulation[34].

Research suggests that taurine might increase the mechanical threshold for skeletal muscle contraction, promote intracellular membrane stabilization, and increase membrane polarization[22]. Taurine has also been noted for its performance enhancing, antioxidant, and nerve conduction effects[22, 35]. Moreover the combination of caffeine and taurine has previously been shown to augment performance to a greater degree than caffeine alone[36].