The primary findings from this investigation were that six weeks of MIPS during RT did not alter CV or metabolic health (blood lipid profile, SBP, DBP, HR, glucose, cortisol, NOx, or hs-CRP) in resistance-trained men. Feelings of vigor and maximal strength increased in both groups regardless of MIPS or Placebo. In addition, six weeks of MIPS in resistance-trained men appear to improve body composition to a greater degree than Placebo. This is in agreement with the results of others who have reported similar findings in untrained participants [12, 13]. These studies also reported an improvement in muscle mass and body composition in untrained men without any deleterious effect on blood safety markers when consuming MIPS either before or before and after RT for four weeks [12, 13]. It has not been determined until now, however, whether MIPS impact CV (e.g. blood lipids, BP, and HR) and/or metabolic (e.g. cortisol) health and body composition in resistance-trained men (a primary marketing target of this class of ergogenic aid). For this reason, we sought to investigate the effects of six weeks of pre- and post-RT MIPS consumption with periodized RT on CV and metabolic health and body fat in resistance-trained men.

Changes in body composition in the current study were dramatic and in some variables, greater than expected based on the current literature. We observed an increase in total body mass in both MIPS (2.9%) and Placebo (1.3%) with MIPS exhibiting a significantly greater gain than Placebo (p = 0.02). Participants in MIPS also increased FFM significantly more than Placebo (+4.2% vs. +1.9%, respectively, p = 0.025). Similar to Shelmadine et al. [12], these gains mirror increases in FFM measured in untrained men after four weeks of RT with a pre-workout only performance supplement that was the same as was used in the present study (SHOT, +4.8% vs. placebo, + 1.7%). In addition, Spillane et al. [13] reported similar findings of increased FFM in untrained men after four weeks of RT when supplementing both pre- and post-RT with the identical performance supplements used in the present study (+3.7%) compared to placebo (+1.0%). It is surprising that our findings so closely mimic the results reported in untrained populations despite our participants averaging 4–7 years of RT experience and substantially higher baseline FFM (+9-13 kg) than participants in the aforementioned studies [12, 13]. The increase in FFM is most likely due to the creatine and/or β-alanine in the product; however, due to the proprietary nature of this supplement, the exact amounts of these ingredients are unknown in the product.

Body fat percent decreased significantly in both groups and this was not solely a function of increased FFM. Total body fat decreased by 2.6 and 3.5% in MIPS and Placebo, respectively. In addition, android (MIPS: -1.8; Placebo: -1.4%) and gynoid fat % (MIPS: -1.3; Placebo: -1.0%) decreased significantly in both groups. Android fat is highly associated with increased risk of CV mortality and diabetes mellitus and thus, it is notable that our RT protocol was successful in reducing both android and gynoid fat. Our findings are supported by research demonstrating that exercise can decrease body fat independent of supplementation [17, 21]. Our prior work has shown increased lipolysis with just one bout of RT in resistance-trained men [4] and in overweight/obese sedentary men [20]. A gain in FFM with concurrent decreases in body fat is a highly desirable goal of athletes in many different sports as well as recreational weight-lifters. Our findings support the supplementation of MIPS in combination with periodized RT as an effective method of improving body composition.

Regarding the multitude of individual ingredients in the proprietary blend of SHOT and SYN, including whey protein, BCAA’s, creatine, caffeine, β-alanine, and L-arginine, it is difficult to isolate their specific effects. In fact, some research suggests a synergistic effect of ingredients in the investigated supplements [22–24]. The increases in FFM we observed may likely be explained by studies that used supplementation of creatine with β-alanine [22] or whey protein and amino acids [23]. Hoffman et al. [22] demonstrated that RT in combination with supplementation of creatine and β-alanine decreased body fat by 1.2% through an increase in lean body mass (LBM) (1.74 ± 1.72 kg) greater than creatine alone (data not reported) or a carbohydrate placebo (0.44 ± 1.62 kg) in collegiate football players. Willoughby et al. [23] observed an increase in FFM of 5.6% when combining 14 g of whey and casein protein with 6 g of free amino acids as compared to a 2.7% increase with a carbohydrate placebo supplement in untrained men following 10 weeks of heavy RT (3 sets of 6–8 reps with 85-90% 1RM, 4×/wk). Perhaps most relevant to the present study, Schmitz et al. [24] recorded 2.4% and 0.27% (p = 0.049) increases in LBM in trained participants (≥ two years RT experience) supplementing with MIPS with and without BCAA’s, respectively. The investigators implemented a nine-week progressive overload RT regimen with participants training four times a week. The two supplements were matched for creatine (4 g), protein (7 g), and carbohydrate (39 g). The supplements from the present study include the primary ingredients from these studies [22–24] and alternative ingredients in a proprietary blend that are purported to improve body composition. Our results suggest that the ingredients in SHOT and SYN may be working together to improve body composition greater than the Placebo.

All measured CV and metabolic variables were within normal clinical ranges at baseline and post-six weeks in the present study. Interventions using various intensities of RT with untrained participants have significantly lowered LDL cholesterol in the same six-week span as the present study [25]. While RT may also improve TRG in untrained individuals [26], our participants were experienced with RT, which likely contributed to the lack of difference measured in these variables. Our findings are supported by previous studies in untrained men [12, 13] using SHOT and SYN, which also report no changes in CV health variables after 4 weeks of RT in men of similar age to participants in the current study.

Cortisol is widely accepted as both a catabolic biomarker and an indicator of overall stress. Based on the current literature, we hypothesized a decrease in cortisol concentration in MIPS but measured no changes. Bird et al. [27] reported that both carbohydrate (6%) and carbohydrate (6%) with essential amino acid supplementation (6 g) during an acute bout of RT suppressed the cortisol response in untrained men compared to a placebo. This may have been due to a glucoregulatory effect in which carbohydrate was an adequate source of energy to prevent the need for cortisol to stimulate the liver to release glucose. Sharp and Pearson [28] demonstrated decreased cortisol concentrations in recreationally active young men after three weeks of BCAA supplementation (6 g/day) followed by a fourth week of supplementation and four bouts of RT (three sets of 6–8 repetitions with 80% 1RM and 60 seconds between sets and exercises, three lower- and five- upper body exercises). The authors reported significant decreases in cortisol 12 hrs after RT bout two, and 12 and 36 hrs after RT bout four. Because of the low-training status of the participants, the RT was deemed an over-reaching training week. Two factors that may have contributed to the differences observed in our data are the experienced training status of our participants and the slightly later (36 vs. 48 hrs) post-training cortisol measurements in the present study. Our data indicate training-status may be a determining factor in resting cortisol concentrations with performance nutrition supplementation.

Total nitrate/nitrite (NOx), which is indicative of production of the potent vasodilator, nitric oxide, was also measured to evaluate the impact on CV health. Nitric oxide is synthesized from L-arginine and L-citrulline, two amino acids present in the MIPS in the present study. Nitric oxide has been reported to improve CV health through vasodilation and prevention of lipid build-up on the arterial walls [29]; however, this finding is specific to diseased populations [30]. We recorded no change in resting NOx within or between groups during the intervention, which agrees with most previously published research [13] in healthy individuals. Interestingly, L-arginine has recently been shown to increase blood volume within the muscle (measured with near-infrared spectroscopy) without changing NOx [31]. It is possible that our participants experienced similar changes in blood volume without the detection of any change in NOx. In addition, by design, we sampled blood 48 hrs following the last training bout to measure the impact of supplementation and training over time rather than acute response to RT.

The inflammatory marker hs-CRP was measured to reflect total body inflammation. Clinical data indicate values of <1, 1–3, >3 mg/L as low, moderate, and high risk, respectively, for CV disease. We recorded no significant changes in hs-CRP within or between groups. Kadaglou et al. [32] recently reported no change in CRP following three months of RT (3×/week) in type two diabetic patients. Conversely, Sheikholeslami et al. [25] demonstrated significantly lower CRP values in untrained men following six weeks of moderate (45-55% 1RM) or high intensity (80-90% 1RM) RT in healthy males compared to a non-intervention control group. The discrepancy in results may be due to the experienced training status of our participants compared to diabetic and untrained individuals. In addition, CRP is notorious for its high intra-subject variability [33] and may have confounded our results.

While RT may independently improve BP in untrained normotensive and pre-hypertensive individuals [26], our data did not indicate changes in BP, perhaps due to our participants’ RT history. Similarly, we saw no changes in HR, likely due to their training status. Research indicates that caffeine, a central ingredient in SHOT, the pre-exercise MIPS used in the present study, can increase HR, SBP, and DBP acutely [9]. Energy drinks with less caffeine than SHOT (80 vs ~190 mg, respectively) have been reported to elevate BP up to 24 hrs after consumption in nine healthy (aged 18–45 years), nonsmoking, normotensive men (n = 4) and women (n = 5) who self-reported to consume between four and 379 mg/day of caffeine (four participants reported habitual caffeine intake) [34]. However, some research suggests chronic coffee drinkers are at a decreased risk for developing CV disease [35]. No published research indicates the HR and BP response to caffeine-containing MIPS.

Regarding mood states, RT elicited an increase in vigor for both MIPS and Placebo. This indicates that it was unlikely our participants were overtrained at the post-testing time point. Bresciani et al. [36] reported a non-significant decrease in vigor and a significant decrease in total mood as being indicative of overtraining in active men.

Resistance-trained men appear to tolerate SHOT and SYN better than their untrained counterparts. Indeed, Shelmadine et al. [12] reported feelings of dizziness, nausea, headache, rapid HR, shortness of breath, and nervousness after consuming SHOT in untrained men. Similarly, Spillane et al. [13] reported select untrained participants experiencing the same side-effects while supplementing with both SHOT and SYN. Only one individual taking SHOT and SYN in the present study reported feeling nauseous while two others reported feelings of paresthesia (although two people in Placebo also reported feeling paresthesia). It is probable that individuals experienced in RT are also experienced with a variety of MIPS and may be more tolerant or less likely to report side effects if any were present.

Limitations

The present study was limited by the accuracy of self-reported dietary intake and supplement consumption on non-training days. However, our research staff collected empty supplement single-serving Ziploc® bags three times per week in an effort to verify compliance and all participants verbally reported no change in eating patterns. Due to the small sample of useable nutrition logs, it is possible that we did not have a representative sample to determine no differences between groups. However, all participants were questioned personally and reported no change in dietary habits for the duration of the six-week study. In addition, differences in prior training status of our participants may have limited our findings; however, even though MIPS had a longer training history (Table 2), they still were able to increase FFM more than Placebo. In addition, those in the MIPS group may have been able to recognize the feelings from the pre-workout supplement that contained caffeine and β-alanine and known they were in the supplement group. Moreover, participants were not monitored 24 hours per day and thus may have been able to discuss how the supplement felt to them. However, all training was completed with limited contact to other participants and any interaction would have been outside of workout and/or laboratory visits. Lastly, we do not have reliability data for the POMS assessment used in this study.