Dr. Fernando Naclerio
Professor in Strength Training and Sports Nutrition
Centre Lead: Centre for Exercise Activity and Rehabilitation Institute for Lifecourse Development
School of Human Sciences
University of Greenwich
Introduction
Pre-workout multi-ingredient (PREW) supplements are designed to acutely enhance exercise performance by combining caffeine with amino acids and other ergogenic aids (Naclerio, 2023). Caffeine (typically 3–6 mg·kg−1) acts via adenosine-receptor antagonism to lower perceived exertion and increase fatty-acid mobilization; formulations often add amino acids such as citrulline/arginine (nitric-oxide precursors), betaine, taurine, and tyrosine to target blood flow, hydration, and cognition (Guest et al., 2021; Trexler et al., 2019).
As part of the Crown Sport Nutrition Project at the University of Greenwich (Centre for Exercise Activity and Rehabilitation), we have evaluated PREW products commercialised by Crown Sport Nutrition in double-blind, randomised controlled trials in middle-aged and older physically active adults; the company provided the tested pre-workouts to the Centre to conduct these studies.
In middle-aged, physically active adults, a caffeinated preworkout (with protein/amino acids and slow-release carbohydrate, such as isomaltulose) acutely increased weekly resistance-training volume and favoured fat oxidation during submaximal cycling versus an isocaloric carbohydrate control (Puente-Fernández et al., 2020). Whether such acute benefits translate into superior training adaptations is less clear. In a 6-week randomised trial with thrice-weekly resistance training, the same PREW and an isocaloric carbohydrate comparator produced similar improvements in fat mass, fat-free mass, muscle thickness, strength, and muscular endurance; only waist circumference showed a modest within-group reduction with PREW (Puente-Fernández et al., 2025).
This short comment synthesises those acute and chronic findings in middle-aged adults, emphasising effects on training volume, substrate oxidation, body composition, and muscle function, and outlines plausible mechanisms relevant to practice.
Study 1 (Puente-Fernández et al., 2020) – 5-Day Training Microcycle
This randomised, double-blind, crossover trial tested the acute effects of a multi-ingredient pre-workout (PREW) versus an isocaloric carbohydrate control (COMP) across a 5-day training microcycle in 14 recreationally trained, middle-aged adults (7 women; ~49 y) in two counterbalanced phases separated by a 2-week washout period. Participants ingested the assigned supplement 15 min pre-workout and completed 3 resistance-training (RT) sessions (full-body circuits targeting ~16 repetitions maximum per set in each exercise) and 2 endurance (END) sessions (30-min cycling at individual previously determined fat max intensity).
Supplementation:
PREW (40 g; ~100 kcal) contained 16 g carbohydrate (predominantly isomaltulose), 9 g protein/amino acids (AAs), including Branched Chain AAs, 400 mg caffeine and 300 mg yerba mate. COMP: 27 g of carbohydrate (maltodextrin); ~102 kcal. Diet was otherwise maintained.
Primary outcomes:
- Resistance-training volume: PREW significantly increased total weekly volume lifted versus COMP (p = 0.001, d = 1.26) and per-workout volume across all three RT sessions (each p < 0.05). Despite higher workloads, session RPE was unchanged between conditions.
- Substrate oxidation: During END, PREW elicited higher fat oxidation (p = 0.046) with a concomitant (non-significant) reduction in carbohydrate oxidation (trend p = 0.07) versus COMP.
Secondary outcomes:
- Post-RT muscle function: The decline in medicine ball throw after the second RT session was smaller with PREW (between-condition p = 0.001). The drop in maximal isometric force after the third session was also smaller with PREW (p = 0.007). Vertical jump showed no between-condition differences.
- Neuromuscular measures: Tensiomyography variables showed no meaningful changes or between-condition differences.
- Subjective responses: Pre-workout energy/focus and post-workout perceived exertion were similar between conditions.
Interpretation
In middle-aged, physically active adults, acutely ingesting a caffeinated, amino-acid-enriched PREW increased RT volume and favoured fat oxidation during low-intensity endurance exercise without increasing perceived effort. PREW also attenuated performance decrements across repeated sessions. No effects were seen on jump performance, tensiomyography, or subjective feelings. These findings support PREW as an acute ergogenic aid for multi-session microcycles, relative to an energy-matched carbohydrate control.
Study 2 (Puente-Fernández et al., 2025) – 6-Week Training Intervention
This 6-week, double-blind, parallel-group randomised controlled trial compared a multi-ingredient pre-workout (PREW) with an isocaloric carbohydrate comparator (COMP) in 43 physically active, middle-aged adults (26 women, 17 men; ~53 ± 5 y). All participants completed supervised RT three times per week with progressive overload. Fifteen minutes pre-workout, participants ingested 30 g of their assigned supplement. PREW was a vegan, protein-enriched formula (9 g protein/amino acids) containing 406 mg caffeine, 300 mg yerba mate, 2.5 g citrulline malate, 2 g betaine, and 1.3 g acetyl-L-carnitine, plus other essential amino acids; to match energy (~60 kcal), PREW included 5 g carbohydrate (maltodextrin), and COMP included 15 g carbohydrate (maltodextrin) with no added protein/actives. Supplements were citrus-flavoured and indistinguishable to preserve blinding. Habitual dietary intake was monitored at baseline and week 6 to minimise confounding; no material between-group differences were detected.
Primary outcomes:
Body composition and muscle size. Both groups reduced fat mass and increased fat-free mass, with no between-group differences. Muscle thickness of the vastus lateralis and elbow flexors increased modestly and similarly in both groups. Results are summarised in Table 1.
Table 1. Changes in body composition and muscle thickness after 6 weeks of training with Pre-Workout (PREW) vs. Carbohydrate (COMP) supplementation. Values are mean changes from pre- to post-training (mean ± SD), with asterisks indicating significant within-group improvement. No between-group differences were statistically significant for these outcomes.
|
Outcome 233922_f58e47-1d> |
PREW (6-week change) 233922_b33b36-1f> |
COMP (6-week change) 233922_cc1dc6-7a> |
|
Fat Mass (kg) 233922_7ae3df-5c> |
−1.4 ± 1.6 233922_cab68b-18> |
−1.0 ± 1.5 233922_e65332-04> |
|
Fat-Free Mass (kg) 233922_06199b-bd> |
+0.9 ± 1.1 233922_17bed5-89> |
+0.8 ± 0.9 233922_15a5ee-41> |
|
Vastus Lateralis thickness (cm) 233922_1d4bdc-14> |
+0.2 ± 0.2 233922_69dd10-80> |
+0.1 ± 0.6 233922_f6778b-2f> |
|
Elbow Flexors thickness (cm) 233922_6ee4b9-4f> |
+0.5 ± 0.3 233922_58e714-21> |
+0.4 ± 0.2 233922_7186bb-89> |
|
Waist Circumference (cm) 233922_c700fe-62> |
−1.8 ± 1.8 233922_358175-84> |
−1.0 ± 1.5 (n.s.) 233922_667d51-64> |
(Values marked bold denote p < 0.05 within that group. “n.s.” = not significant. Between-group comparisons were n.s. for all measures.)
The only metric with a notable within-group effect unique to PREW was waist circumference, which decreased significantly (−1.8 ± 1.8 cm; p < 0.01 vs baseline). The COMP group showed a smaller, non-significant decrease (−1.0 ± 1.5 cm). However, the between-group comparison for waist did not reach statistical significance, indicating that PREW did not outperform COMP on central adiposity reduction.
Secondary outcomes:
Performance and training dose. Both groups improved isometric strength, vertical jump height, medicine ball throw distance, and 30-s sit-to-stand/bench-press repetitions (training-induced gains), with no significant between-group differences after adjusting for baseline. Across the intervention, total training volume (cumulative load lifted in kg) increased comparably in PREW and COMP, and the global Rate of Perceived Exertion (RPE) measure about 20 post workout was similar, suggesting the pre-workout did not systematically alter perceived effort or allow a higher realised training dose within this prescribed programme.
Interpretation:
When training volume and energy intake are matched, PREW did not confer additional long-term benefits over an isocaloric carbohydrate supplement in middle-aged, physically active adults. Both strategies supported meaningful improvements in body composition and performance over 6 weeks; PREW’s only distinctive finding was a within-group reduction in waist circumference that did not translate into a between-group advantage. These results underscore that the training stimulus, with adequate nutrition, was the principal driver of adaptation in this population.
Discussion and recommendations
Across two complementary trials in middle-aged, physically active adults, multi-ingredient pre-workout supplementation showed a clear acute ergogenic effect but no additional long-term advantage over an isocaloric carbohydrate comparator when the training dose was matched.
In the acute 1-microcycle trial, ingesting PREW 15 min pre-workout increased resistance-training volume across all three sessions within the week and shifted substrate use toward higher fat oxidation during low-intensity cycling, without raising perceived exertion. PREW also attenuated post-workout decrements in medicine ball throw and isometric strength versus carbohydrate alone (energy-matched). These findings support PREW as a short-term aid to sustain output and manage fatigue across dense training microcycles.
In the 6-week interventional RCT study. With supervised, thrice-weekly resistance training and matched pre-exercise energy, PREW and carbohydrate produced similar improvements in fat mass (~ −1.0 to −1.4 kg), fat-free mass (~ +0.8 to +0.9 kg), muscle thickness (vastus lateralis and elbow flexors), maximal isometric strength, vertical jump, medicine-ball throw, and 30-s muscular-endurance tests. Waist circumference decreased significantly within the PREW group (~ −1.8 ± 1.8 cm), but the between-group difference versus carbohydrate was not significant, indicating no confirmed superiority for central adiposity reduction. Total training volume and session RPE progressed similarly in both groups, suggesting PREW did not increase the realised dose within this programme.
Mechanistic context:
The acute benefits align with caffeine’s adenosine-receptor antagonism (lower perceived exertion, higher arousal) and lipolytic/thermogenic actions; 3–6 mg·kg−1 is typically ergogenic when timed ~30–60 min pre-exercise, with inter-individual variability (Guest et al., 2021). Additional PREW components (e.g.,citrulline/arginine as NO precursors, betaine and taurine) may support blood flow, hydration, and fatigue resistance; pooled evidence shows small but significant benefits of citrulline for high-intensity strength/power (Trexler et al., 2019). In the 6-week trial, however, any acute edge likely did not translate because training was prescribed and equated; the dominant driver of adaptation was the training stimulus supported by adequate energy and protein ingestion.
Practice recommendations:
- Use PREW strategically to bolster acute session quality (e.g., demanding microcycles, low-sleep/low-motivation days, or when extra volume is programmed). Expect more repetitions at a given intensity, total load at the same perceived effort, useful if your plan allows that extra work to accrue.
- Do not expect superior long-term outcomes vs. an isocaloric carbohydrate pre-exercise drink unless PREW helps you consistently realise higher training volume or intensity over time (and recovery is managed).
- Dose/timing: Start at ~3 up to 6 mg·kg−1 caffeine 30–60 min pre-workout; titrate up only if tolerated. Avoid late-day use to protect sleep; consider cycling use to limit habituation (Guest et al., 2021).
- Safety/individualisation: Screen for caffeine sensitivity, hypertension, arrhythmia, pregnancy, and drug interactions. For stimulant-averse athletes, carbohydrate-only pre-exercise is a valid alternative that supported similar 6-week adaptations (Puente- Fernández et al., 2025).
- Prioritise fundamentals: Progressively overloaded training, sufficient daily high-quality protein (1.6 to 2 g.kg-1.BM-1)(Naclerio & Seijo, 2019) and energy intake, sleep, and recovery practices will govern outcomes; supplements are adjuncts, not substitutes.
Bottom line: In middle-aged and older active individuals, PREW is an effective acute aid but not a guaranteed driver of superior chronic adaptations when energy and training volume are matched.
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References
Guest, N. S., VanDusseldorp, T. A., Nelson, M. T., Grgic, J., Schoenfeld, B. J., Jenkins, N. D. M., Arent, S. M., Antonio, J., Stout, J. R., Trexler, E. T., Smith-Ryan, A. E., Goldstein, E. R., Kalman, D. S., & Campbell, B. I. (2021). International society of sports nutrition position stand: caffeine and exercise performance. Journal of the International Society of Sports Nutrition, 18(1), 1–37. https://doi.org/10.1186/s12970-020-00383-4
Naclerio, F. (2023). Supplementation with Multi-Ingredients for Physically Active Individuals. Revista Iberoamericana de Ciencias de La Actividad Física y El Deporte, 12(3), 42–51. https://doi.org/10.24310/riccafd.12.3.2023.17761
Naclerio, F., & Seijo, M. (2019). Whey protein supplementation and muscle mass: current perspectives. Nutrition and Dietary Supplements, 11, 37–48. https://doi.org/10.2147/nds.s166195
Puente-Fernández, J., Larumbe-Zabala, E., Roberts, J., & Naclerio, F. (2025). Pre-workout multi-ingredients or carbohydrate alone promote similar resistance training outcomes in middle-aged adults: a double-blind, randomized controlled trial. Journal of the International Society of Sports Nutrition, 22(1). https://doi.org/10.1080/15502783.2025.2519515
Puente-Fernández, J., Seijo, M., Larumbe-zabala, E., Jiménez, A., Liguori, G., Rossato, C. J. L., Mayo, X., & Naclerio, F. (2020). Effects of multi-ingredient preworkout supplementation across a five-day resistance and endurance training microcycle in middle-aged adults. Nutrients, 12(12), 1–19. https://doi.org/10.3390/nu12123778
Trexler, E. T., Persky, A. M., Ryan, E. D., Schwartz, T. A., Stoner, L., & Smith-Ryan, A. E. (2019). Acute Effects of Citrulline Supplementation on High-Intensity Strength and Power Performance: A Systematic Review and Meta-Analysis. Sports Medicine, 49(5), 707–718. https://doi.org/10.1007/s40279-019-01091-z
