RCTJadad 2/5RandomizedDouble-BlindPlacebo-Controlled

Pre-Workout Supplements Over 8 Weeks: What Actually Happens Once the "Kick" Wears Off

Journal of the International Society of Sports NutritionJanuary 3, 2017Vol. 14

Summary

If you've ever wondered whether that tingly, energized pre-workout you scoop before leg day actually pays off over months of training — or whether "fat-burner" add-ins like synephrine are worth the extra cost — this study offers some rare long-term data. Most pre-workout research looks at a single workout. This one followed 80 resistance-trained men for a full 8 weeks of structured training while they drank one of three things daily: a placebo, a market pre-workout supplement (PWS, modeled on Cellucor's C4 Pre-Workout — beta-alanine, creatine nitrate, arginine, tyrosine, 284 mg caffeine, a small dose of L-Dopa from Mucuna pruriens, and B-vitamins), or that same PWS plus 20 mg of synephrine from Citrus aurantium (bitter orange), a "fat-burning" stimulant found in many thermogenic products. It was randomized, double-blind, and placebo-controlled — the gold-standard design — though the actual randomization method wasn't described in enough detail to verify it was truly random (more on that in Caveats).

The headline finding: everyone got stronger and leaner over 8 weeks — bench press 1RM rose by roughly 7-14 kg and leg press by 43-90 kg across groups — but statistically, the supplement groups weren't significantly better than placebo by week 8. There WAS a more interesting early pattern: at the 4-week mark, the supplement groups (PWS and PWS+synephrine) showed clearer strength gains and better cognitive test scores (Stroop test, which measures focus and reaction speed under mental fatigue) than placebo, whose gains weren't yet statistically distinguishable from zero. By week 8, the placebo group had "caught up," making the groups statistically indistinguishable. This "fades over time" pattern showed up for both strength and cognition, suggesting an early psychological or acute-stimulant edge that training itself eventually equals out.

For body composition — the outcome most people buy fat burners for — there was no meaningful difference between the groups: fat mass, body fat percentage, and lean mass all moved similarly whether people took placebo, the PWS, or the PWS with synephrine. Adding synephrine didn't help you lose more fat or build more muscle than the caffeine-and-amino-acid formula alone. On the safety side, the news was good: no meaningful changes in resting heart rate, blood pressure, or blood chemistry markers, and reported side effects (dizziness, racing heart, nervousness) were rare and no different from placebo — reassuring for a product combining nearly 300 mg of caffeine with a stimulant-adjacent citrus extract.

What This Means For You

If you're already using a caffeine-and-amino-acid pre-workout, this study suggests it may sharpen focus and give you a strength edge in the first several weeks of a new program — useful during that early "motivation window" — but don't expect it to outperform disciplined training and diet by week 8. The 284 mg caffeine dose used here (~3.5 mg/kg) sits within the well-supported 3-6 mg/kg range for performance and alertness; check your own product's label, since many pre-workouts stack 300-400 mg per scoop, which adds up fast if you're also drinking coffee. The 3 g beta-alanine and 2 g creatine doses are consistent with maintenance-level dosing — enough to sustain existing stores but likely too low (especially the creatine) to drive dramatic new gains; if creatine is your primary goal, a dedicated 3-5 g/day monohydrate product is better evidenced.

For synephrine/bitter-orange "fat burner" add-ins specifically: this trial found no added fat-loss or muscle-gain benefit from 20 mg/day over 8 weeks, and the authors note this dose was notably lower than doses (49-98 mg/day) used in trials that did report weight-loss effects. So if a product is marketing synephrine for body composition, the effective dose (and total stimulant load when stacked with caffeine) matters more than its mere presence on the label — and higher doses have less safety data behind them.

Best candidates for this type of pre-workout: caffeine-tolerant, healthy resistance-trained adults wanting an early-program focus/strength boost. People with hypertension, arrhythmia, thyroid conditions, or stimulant sensitivity should be cautious or consult a physician, as this trial explicitly excluded those groups — its safety findings don't generalize to them.

Important Considerations

This trial only enrolled young (~22 years old), healthy, already resistance-trained men — results may not apply to women, older adults, beginners, or anyone with cardiovascular, metabolic, or thyroid conditions, all of whom were excluded by design. The Jadad quality score was low (2/5): while blinding was well-described and credible, the randomization method itself was never specified (participants were "matched" and "randomized" but the actual sequence-generation technique is unreported), and dropout/withdrawal numbers between the 122 people who started and the 80 who finished weren't broken down or explained. That's a meaningful gap — we don't know if certain groups lost more participants than others in a way that could bias results.

The study was funded by Nutrabolt, the maker of the exact product tested (Cellucor C4), and two authors hold formal advisory/consulting roles with the sponsor — a common but real conflict-of-interest in supplement research that warrants extra skepticism, even though the university reports an oversight plan was in place. The trial was also registered on ClinicalTrials.gov after it was already completed (retrospective registration), which reduces confidence that all planned outcomes were reported as originally intended. Many of the "significant" findings reported (like the week-4 strength and cognition boosts) came from secondary analyses of mean changes and confidence intervals rather than the primary overall statistical test, which did not reach significance — a pattern worth watching for in supplement marketing generally, since secondary/subgroup findings are more prone to false positives than primary endpoints. Finally, this is one 8-week study of one specific formulation — it doesn't tell you how these ingredients perform individually, at different doses, or over longer timeframes. Anyone with heart, thyroid, or blood pressure conditions should talk to a doctor before combining caffeine-heavy pre-workouts with additional stimulants like synephrine.

Terms Explained

1RM (One-Rep Max)The maximum weight a person can lift for a single repetition of an exercise, used here to measure bench press and leg press strength gains.

Beta-alanineAn amino acid supplement (typically 3-6 g/day) that raises muscle carnosine levels, helping buffer acid buildup during high-intensity exercise.

Synephrine (Citrus aurantium / bitter orange)A stimulant-like plant compound marketed in 'fat burner' and pre-workout products for its purported effects on metabolism and fat oxidation.

Double-blind, placebo-controlledA study design where neither participants nor researchers know who receives the real treatment versus an inactive placebo, reducing bias in results.

DXA scan (dual-energy X-ray absorptiometry)A precise body-composition imaging method used to measure fat mass, lean mass, and bone density.

Stroop testA cognitive test measuring attention, processing speed, and mental focus, often used to gauge how well someone maintains concentration under fatigue.

Wingate testA 30-second all-out cycling sprint test used to measure anaerobic power and short-burst athletic performance.

Jadad scoreA 0-5 scale rating a clinical trial's methodological quality based on randomization, blinding, and reporting of dropouts; higher is more rigorous.

Group x time interactionThe statistical test showing whether one group changed differently than another over the course of the study, as opposed to all groups simply changing similarly with time.

Technical Study Details

Study Design

Duration8 weeks

RegistrationClinicalTrials.gov: NCT02999581

Total Score

JADAD Quality Assessment

/ 5

評価詳細

Randomization

0 / 2

Is the study described as randomized?

Yes+1

Rationale: The article explicitly and repeatedly describes the study as "randomized" — in the Methods overview ("prospective, randomized, double-blind, and placebo controlled cohort study"), in the Abstract ("randomly assigned"), and in the detailed methods ("randomized into one of three dietary supplement intervention arms in a randomized manner" and "randomly assigned to ingest in a double-blind manner").

Is the method of randomization described and appropriate?

No-1

Rationale: The article states participants were "randomized" and "randomly assigned" to groups, but it does not describe the actual method used to generate the random allocation sequence (e.g., computer-generated random numbers, random number table, coin toss). Without a description of the specific randomization technique, the appropriateness of the method cannot be verified, so per Jadad scale scoring this should be answered "no."

Blinding

2 / 2

Is the study described as double-blind?

Yes+1

Rationale: The Methods section explicitly states the study was conducted as a 'double-blind' study, and this is reiterated in the Abstract and Supplementation protocol sections describing supplement assignment in a 'double-blind manner' with coded packets for 'double-blind administration'.

Is the method of blinding described and appropriate?

Yes+1

Rationale: The Methods section (Supplementation protocol) describes the blinding method in detail: supplements (placebo, PWS, and PWS+S) were independently packaged by a third party into coded single foil packets, and all supplements had similar color and powdered texture. This is an appropriate double-blinding method because participants and researchers could not distinguish between conditions based on appearance/texture, satisfying the Jadad criterion for appropriate blinding.</rationale> </invoke>

Dropouts/Withdrawals

0 / 1

Is there a description of dropouts and withdrawals?

No0

Rationale: The article reports the number of individuals screened (213), cleared to participate (122), and who ultimately completed the study (80, broken down by group: PLA=27, PWS=27, PWS+S=26). However, it never explicitly states how many participants withdrew or dropped out at each stage, nor does it give any reasons for withdrawal/dropout per treatment group, which is required to satisfy the Jadad criterion for this item.

Study Population

Sample Size80

Age RangeMean: 22 years

ConditionApparently healthy, resistance-trained males undergoing 8-week periodized resistance training

Inclusion Criteria

At least 6 months of resistance training immediately prior to entering the study, inclusive of performing bench press and leg press or squat

Interventions

Placebo (dextrose)

Control

FrequencyOnce daily (~15-30 min prior to exercise on training days; with breakfast on non-training days)

Duration8 weeks

Routeoral

PWS (Cellucor C4 Pre-Workout)

Treatment

Dose1 packet/day

FrequencyOnce daily (~15-30 min prior to exercise on training days; with breakfast on non-training days)

Duration8 weeks

Routeoral

PWS + Synephrine

Treatment

Dose20 mg synephrine/day (1 packet/day)

FrequencyOnce daily (~15-30 min prior to exercise on training days; with breakfast on non-training days)

Duration8 weeks

Routeoral

Outcomes

Outcome	Type	Effect	p-value
Body Weight	Secondary	-	time p=0.003; group x time p=0.28
Fat Mass	Secondary	-	group x time p=0.61
Fat Free Mass	Secondary	-	time p=0.001; group x time p=0.28
Body Fat Percentage	Secondary	-	group x time p=0.36
Total Body Water Percentage	Secondary	-	group x time p=0.37
Resting Heart Rate	Secondary	-	p=0.26
Systolic Blood Pressure	Secondary	-	p=0.96
Diastolic Blood Pressure	Secondary	-	p=0.54
Stroop Word Count	Secondary	-	-
Stroop Color Count	Secondary	-	interaction trend p=0.087
Stroop Word-Color Count	Secondary	-	quadratic effect p=0.04
Readiness to Perform (VAS composite)	Secondary	-	group p=0.27; time p<0.001; group x time p=0.66
Bench Press 1RM	Primary	-	-
Leg Press 1RM	Primary	-	-
Wingate Peak Power	Primary	-	-Significant
Wingate Mean Power	Primary	-	-
Wingate Total Work	Primary	-	-
Total Lifting Volume (upper/lower extremity)	Secondary	-	group p=0.69
Relative Energy Intake	Secondary	-	p=0.19
Protein Intake	Secondary	-	p=0.72
Carbohydrate Intake	Secondary	-	p=0.55
Fat Intake	Secondary	-	p=0.79
Muscle and Liver Enzymes / Markers of Catabolism (ALP, AST, ALT, creatinine, BUN, CK, LDH)	Secondary	-	group p=0.43; time p<0.001; group x time p=0.66
Blood Glucose and Lipid Panel	Secondary	-	group p=0.44; time p<0.001; group x time p=0.58
Complete Blood Count with Differential	Secondary	-	group p=0.78; time p=0.06; group x time p=0.013Significant
Prevalence of Blood Chemistry Values Exceeding Normal Clinical Bounds	Secondary	-	-
Reported Side Effects (dizziness, headache, racing heart, palpitations, shortness of breath, nervousness, blurred vision, other)	Secondary	-	-

Safety

Serious AEs0

Reported frequency and severity of dizziness, headaches, racing heart rate, palpitations, shortness of breath, nervousness, blurred vision, and/or other symptoms were so infrequent among participants (90-98% reported 0 ratings on each item throughout the study) that statistical analysis was not valid. No study participant required medical referral. No significant group x time interactions were observed in blood chemistry panels, and no significant differences were observed in the number of participants with blood values exceeding normal clinical limits (Table 11, chi-square).

Conclusion

Eight weeks of PWS and PWS+S supplementation during resistance training improved some indices of cognitive function and exercise performance (particularly at 4 weeks) without significant side effects in apparently healthy males, but these effects were largely similar to placebo by 8 weeks, and adding 20 mg of synephrine to the PWS did not provide additive benefits over the PWS alone for body composition, cognitive function, or exercise performance.

Limitations

The amount of synephrine provided (20 mg/day) was lower than doses used in other studies reporting weight/fat loss effects (e.g., 49-98 mg/day in Kaats et al.), which may explain the lack of additive body composition benefit.
Performance tests used (1RM strength, Wingate anaerobic capacity) may not require significant executive/cognitive functioning, potentially limiting the ability to detect a relationship between improved cognitive function and exercise performance.
Apparent ergogenic benefits of PWS on cognitive function and strength observed at 4 weeks were not sustained relative to placebo by 8 weeks, suggesting effects may lessen over time with continued use.
Trial was retrospectively registered on ClinicalTrials.gov (December 16, 2016), after study conduct.
No significant overall MANOVA interactions were found for most outcomes, so many between-group differences reported are based on secondary analyses (baseline-covariate MANOVA and 95% CI comparisons) rather than the primary omnibus test.