Pre-workout stack — evidence-graded ergogenic aids without the proprietary blend
Commercial pre-workouts hide modest doses of two or three things that actually work behind a wall of fillers, undisclosed-dose proprietary blends, novel stimulants, and "nitric oxide boosters" with no human endpoint data. This stack rebuilds a pre-workout session-support set from individually-dosed ingredients with replicated performance evidence. Foundation layer handles the substrate side. Performance layer handles the acute session boost. Optional layer addresses event-specific needs (sprint repeats, sustained high-intensity, low-sleep training days).
Commercial pre-workouts hide modest doses of two or three things that actually work behind a wall of fillers, undisclosed-dose proprietary blends, novel stimulants, and "nitric oxide boosters" with no human endpoint data. This stack rebuilds a pre-workout session-support set from individually-dosed ingredients with replicated performance evidence.
Built for adults training 4–6 days per week — resistance work, intervals, repeated-sprint sports, or endurance. Not designed for caffeine-naive beginners (start lower) and not for anyone with arrhythmias, uncontrolled hypertension, or who is pregnant or breastfeeding. Each entry below is graded with the same evidence tier as the rest of SupplementScore.
TL;DR — the stack
| Supplement | Layer | Dose & timing | Score |
|---|---|---|---|
| Creatine monohydrate | Foundation | 3–5 g daily, any time (not session-timed) | 96 |
| Beta-alanine | Foundation | 3.2–6.4 g/day, split, chronic loading | 71 |
| Caffeine (standardised) | Performance | 3–6 mg/kg, 30–60 min pre-session | 88 |
| Citrulline malate | Performance | 6–8 g, 45–60 min pre-session | 68 |
| Dietary nitrate / beetroot | Performance | 400–800 mg NO₃⁻ (≈70–140 mL concentrate), 2–3 h pre-session | 72 |
| Sodium bicarbonate | Optional | 0.2–0.3 g/kg, 60–180 min pre-session (split doses) | 66 |
| Tyrosine (L-tyrosine) | Optional | 100–150 mg/kg, 30–60 min pre-session (sleep-deprived/stress days) | 58 |
| Taurine | Optional | 1–3 g, 60–120 min pre-session | 55 |
Per-supplement detail
Dose & timing. 3–5 g daily, any time of day, with or without food. Optional load (20 g/day × 5 d) saturates phosphocreatine faster; daily 5 g reaches the same plateau in ≈4 weeks. Pre- or post-session timing is not meaningful — chronic saturation is what matters.
Why. Creatine restores phosphocreatine between high-intensity bouts and is the most heavily studied performance supplement in existence. The Kreider et al. 2017 ISSN position stand (PMID 28615996) reviewed hundreds of trials and concluded creatine is safe and effective for high-intensity exercise performance, repeated-bout work, and lean-mass gains. Effects on 1-rep-max strength and total work in sets-to-failure replicate across resistance-trained and untrained populations.
Funder mix. Mix of academic, ISSN-affiliated, and supplement-industry trials. Independent meta-analyses replicate the effect.
Notes. Monohydrate is the form with the evidence — HCl, "buffered" and other variants have not outperformed it in head-to-head studies and cost more. Transient water-weight gain (~1 kg) is expected.
Dose & timing. 3.2–6.4 g/day in 800 mg–1.6 g split doses (paresthesia is dose-dependent). Not session-timed — chronic loading saturates muscle carnosine over ≥4 weeks. Sustained-release Carnosyn-style forms reduce tingling.
Why. Beta-alanine raises muscle carnosine, buffering hydrogen-ion accumulation in repeated high-intensity efforts. Saunders et al. 2017 (PMID 27797728) meta-analysed 40 trials and found beta-alanine improved 1–4 minute exercise capacity by ≈2.85% — meaningful for repeated-sprint sports (CrossFit, rowing, sprint cycling, MMA), 400–800 m efforts, and back-end sets of 10–20 reps. Effect is smaller for <30 s pure-strength efforts and >10 min endurance.
Funder mix. ISSN-affiliated and academic; some industry funding for Carnosyn-form trials.
Notes. Tingling/paresthesia is harmless. Skip if your training is purely sub-10-rep strength sets — minimal benefit.
Dose & timing. 3–6 mg/kg bodyweight, 30–60 min before the session. Use anhydrous caffeine capsules or tablets for precise dosing; coffee is fine but variable. Cap evening sessions at ≤2 mg/kg or skip — caffeine's half-life is 5–6 h and disrupts sleep architecture even when you "fall asleep fine".
Why. Caffeine is the most replicated ergogenic aid in the literature. Guest et al. 2021 (PMID 33388079) — the ISSN position stand on caffeine and exercise performance — reviewed hundreds of RCTs and concluded ergogenic effects of 2–8% across aerobic endurance, repeated-sprint work, strength-power, and muscular endurance, plus consistent reductions in perceived exertion. Grgic et al. 2018 (PMID 30086762) meta-analysed and confirmed strength and power gains specifically.
Funder mix. Largely academic with mixed industry involvement; meta-analytic effect replicates across funder categories.
Notes. CYP1A2 genotype moderates response (slow metabolisers get smaller ergogenic effects and more sleep disruption). Tolerance develops within 4–7 d; cycling once weekly preserves acute response. Habitual users still get an ergogenic effect — abstinence withdrawal is not required.
Dose & timing. 6–8 g citrulline malate (≈3.4–4.5 g L-citrulline), 45–60 min before training. Pure L-citrulline at 3–5 g works equivalently.
Why. Oral citrulline is converted to arginine in the kidneys more efficiently than oral arginine itself, raising plasma arginine and NO substrate availability. Trexler et al. 2019 (PMID 31185281) meta-analysed 12 RCTs and found citrulline supplementation produced a small but significant improvement in high-intensity strength and power performance (effect size ≈0.20) — translating to one or two extra reps on back-off sets at the same load. Pérez-Guisado and Jakeman 2010 (PMID 20386132) originally documented the reduced-perceived-exertion and reps-to-failure effect.
Funder mix. Mostly academic; some supplement-industry trials. Effect size is small but consistent.
Notes. Sour-pucker taste; mix with electrolytes/water. Effect is more visible in resistance-training endurance than in 1RM tests. Don't combine with PDE-5 inhibitors (sildenafil/tadalafil) — additive hypotension risk.
Dose & timing. 400–800 mg nitrate (≈70–140 mL of a standardised concentrate, or ≈500 mL whole beetroot juice), taken 2–3 hours before the session. Chronic dosing (3–6 d) compounds the effect for endurance events.
Why. Dietary nitrate is reduced to nitrite by oral bacteria and to NO in vivo, improving mitochondrial efficiency and reducing the O₂ cost of submaximal work. Domínguez et al. 2017 (PMID 28067808) meta-analysed 23 RCTs and found nitrate improved time-to-exhaustion at submaximal intensities, with smaller but real effects on time-trial performance in middle-distance events. Effect is largest in recreational athletes; well-trained elites get a smaller response.
Funder mix. Mostly academic plus some beetroot-industry-funded sport science trials.
Notes. Do not use antibacterial mouthwash before dosing — it kills the oral bacteria responsible for nitrate reduction and abolishes the effect (Govoni et al. 2008, PMID 18568048). Pink urine and stools (beeturia) are harmless. Stack carefully with antihypertensives.
Dose & timing. 0.2–0.3 g/kg bodyweight, ingested 60–180 min before high-intensity work. Split into 3–4 doses 15 min apart and take with a carbohydrate-containing meal to minimise GI distress. Enteric-coated forms (Maurten Bicarb or equivalent) substantially reduce GI symptoms.
Why. Bicarbonate raises extracellular pH, providing a sink for muscle-derived H⁺ during high-intensity work. Grgic et al. 2021 (PMID 33677792) meta-analysed 39 trials and found a small-to-moderate ergogenic effect (≈1.7%) for events lasting 30 s to 12 min — strongest in 1–7 min sustained high-intensity efforts (400–1500 m running, 200–400 m swimming, rowing 1k–2k, repeated sprints).
Funder mix. Academic and university sport-science departments.
Notes. Diarrhoea and bloating are common with non-coated forms — test in training, never on race day untested. Avoid with hypertension medication that retains sodium (high sodium load). Useful for 800 m runners, MMA, CrossFit, rowing; useless for max-strength singles or marathon-distance work.
Dose & timing. 100–150 mg/kg bodyweight (≈7–12 g for most adults), 30–60 min before the session. Reserve for sleep-deprived training days or back-to-back sessions where cognitive load is high.
Why. Tyrosine is the substrate for catecholamine synthesis (dopamine, noradrenaline). Under acute stress — sleep deprivation, cold, sustained vigilance — tyrosine becomes rate-limiting. Jongkees et al. 2015 (PMID 26424423) reviewed 15 RCTs and found tyrosine consistently improved cognitive performance under stress and acute fatigue, with smaller effects in well-rested subjects. The relevance for training: cognitive control of effort is what limits the last sets of a hard session when you're under-slept.
Funder mix. Mostly academic and military-funded cognitive-performance trials.
Notes. No additive benefit in well-rested, well-fed athletes. Skip if you take MAOIs (theoretical interaction). Effect on pure-strength performance is small to absent.
Dose & timing. 1–3 g, 60–120 min before the session.
Why. Taurine has small but replicable ergogenic effects on endurance and repeated-bout performance, with mechanism involving Ca²⁺ handling in skeletal muscle and antioxidant capacity. Waldron et al. 2018 (PMID 29347855) meta-analysed 10 endurance-performance trials and found a small ergogenic effect at 1–3 g acute doses (effect size ≈0.40). Effects on resistance work are smaller and less consistent.
Funder mix. Academic and university sport-science departments.
Notes. The taurine in energy drinks is at the right dose to plausibly contribute to the ergogenic effect — but the caffeine is doing most of the work. Generally well-tolerated.
Daily timing — when to take what
MiddayBeta-alanine 1.6 g (second split dose). Sodium bicarbonate dose 1 of 3 (T-180 min from training, if used).
T-60 to T-90Citrulline malate 6–8 g. Tyrosine (if used, on stress/sleep-debt days only). Last bicarbonate dose. Beetroot may already be in (was taken T-2 to T-3 h ago).
T-30 to T-60Caffeine 3–6 mg/kg. Taurine 1–3 g (if used).
Post-sessionSee the post-workout recovery stack for substrate, anti-inflammatory and adaptation support.
Within-stack synergies
The Foundation pair of creatine + beta-alanine is additive across repeated high-intensity bouts — different mechanisms (phosphocreatine restoration vs intramuscular pH buffering). Hoffman et al. 2006 (PMID 16922911) showed additive strength and power gains when both were trained chronically. Combining them during the loading phase saves you weeks.
Caffeine + citrulline work cleanly together — caffeine reduces perceived exertion and citrulline modestly extends reps-to-failure at the same load. There's no documented antagonism.
Sodium bicarbonate + beta-alanine have been studied together for repeated-sprint events and the combination produces additive or near-additive ergogenic effects (Bellinger et al. 2012, PMID 22158262) — the buffering happens at intracellular (carnosine) and extracellular (HCO₃⁻) sites.
Beetroot/nitrate + caffeine have a small documented antagonism in some studies of endurance — caffeine may attenuate the O₂-cost reduction nitrate produces. For pure endurance use, separate or trial individually; for mixed-intensity work, combine and assess.
Interactions to watch
- Caffeine + stimulant medication (ADHD treatments, decongestants). Additive cardiovascular load (BP, HR). Halve the caffeine dose and skip on days with PRN stimulants.
- Caffeine + lithium. Caffeine reduces lithium levels via diuresis; abrupt caffeine changes can destabilise lithium-managed psychiatric conditions.
- Beetroot/nitrate + antihypertensives. Additive BP-lowering — measure home BP before and after introducing nitrate if you're on ACE-i, ARB, beta-blocker, or diuretic.
- Citrulline + PDE-5 inhibitors (sildenafil, tadalafil). Additive hypotension risk. Avoid combining acutely.
- Sodium bicarbonate + sodium-retaining antihypertensives or lithium. The sodium load (≈70 mmol per dose) is meaningful for salt-sensitive hypertension and shifts lithium clearance. Avoid bicarbonate loading if you're on lithium.
- Creatine + kidney disease (eGFR < 60). Creatine is generally safe at 3–5 g/day in healthy kidneys, but get nephrology sign-off if eGFR is reduced. Serum creatinine rises ≈0.2 mg/dL on creatine and is not indicative of kidney injury — use cystatin C for accurate GFR.
- Beetroot mouthwash interaction. Antibacterial mouthwash (chlorhexidine, alcohol-based) kills the oral nitrate-reducing bacteria and abolishes the ergogenic effect. Don't combine on training days.
- Pregnancy / breastfeeding. Cap caffeine at ≤200 mg/day per ACOG (≤2 mg/kg). Skip the rest of the Performance and Optional layers — pre-workout supplements are not studied in pregnancy. Whey, creatine and standard nutrition cover the substrate side.
Don't bother — what to skip
These are commonly bundled into commercial pre-workouts but the evidence does not hold up, or holds up only in subgroups the labelling doesn't disclose.
- L-arginine for "NO boost". Oral arginine is poorly absorbed and largely degraded by intestinal arginase, so it doesn't reliably raise plasma arginine the way citrulline does. Álvares et al. 2012 (PMID 22260513) reviewed the human evidence and concluded acute oral arginine does not consistently improve exercise performance in healthy adults. If you want NO substrate, take citrulline.
- BCAAs as a pre-workout. Branched-chain amino acids alone do not maximally stimulate muscle-protein synthesis — you need the full essential amino acid (EAA) profile. Wolfe 2017 (PMID 28852372) reviewed the mechanism and concluded BCAA-only products cannot drive MPS without the other six EAAs, because the muscle becomes substrate-limited within minutes. If you already eat enough protein or take whey/EAA, pre-workout BCAAs add nothing.
- DMAA / DMHA novel-stimulant pre-workouts. These have been the subject of FDA warning letters and case reports of hypertensive crisis, cardiac events, and at least one death. Cohen et al. 2014 (PMID 24176010) documented continued availability in commercial pre-workouts despite the FDA action. No human ergogenic trial supports the risk profile.
- Deer antler velvet "IGF-1". Marketed as a recovery and performance enhancer based on trace IGF-1 content. Sleivert et al. 2003 (PMID 14620794) tested deer antler velvet against placebo in resistance-trained men and found no effect on strength, body composition, or aerobic fitness. The oral IGF-1 content does not survive digestion in any meaningful way.
Sources
- Kreider RB, Kalman DS, Antonio J, et al. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017;14:18. PMID: 28615996.
- Saunders B, Elliott-Sale K, Artioli GG, et al. β-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis. Br J Sports Med. 2017;51(8):658–669. PMID: 27797728.
- Guest NS, VanDusseldorp TA, Nelson MT, et al. International Society of Sports Nutrition position stand: caffeine and exercise performance. J Int Soc Sports Nutr. 2021;18(1):1. PMID: 33388079.
- Grgic J, Trexler ET, Lazinica B, Pedisic Z. Effects of caffeine intake on muscle strength and power: a systematic review and meta-analysis. J Int Soc Sports Nutr. 2018;15:11. PMID: 30086762.
- Trexler ET, Persky AM, Ryan ED, et al. Acute effects of citrulline supplementation on high-intensity strength and power performance: a systematic review and meta-analysis. Sports Med. 2019;49(5):707–718. PMID: 31185281.
- Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. 2010;24(5):1215–1222. PMID: 20386132.
- Domínguez R, Cuenca E, Maté-Muñoz JL, et al. Effects of beetroot juice supplementation on cardiorespiratory endurance in athletes: a systematic review. Nutrients. 2017;9(1):43. PMID: 28067808.
- Govoni M, Jansson EÅ, Weitzberg E, Lundberg JO. The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash. Nitric Oxide. 2008;19(4):333–337. PMID: 18568048.
- Grgic J, Pedisic Z, Saunders B, et al. International Society of Sports Nutrition position stand: sodium bicarbonate and exercise performance. J Int Soc Sports Nutr. 2021;18(1):61. PMID: 33677792.
- Jongkees BJ, Hommel B, Kühn S, Colzato LS. Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands — a review. J Psychiatr Res. 2015;70:50–57. PMID: 26424423.
- Waldron M, Patterson SD, Tallent J, Jeffries O. The effects of an oral taurine dose and supplementation period on endurance exercise performance in humans: a meta-analysis. Sports Med. 2018;48(5):1247–1253. PMID: 29347855.
- Hoffman J, Ratamess NA, Kang J, et al. Effect of creatine and β-alanine supplementation on performance and endocrine responses in strength/power athletes. Int J Sport Nutr Exerc Metab. 2006;16(4):430–446. PMID: 16922911.
- Bellinger PM, Howe ST, Shing CM, Fell JW. Effect of combined β-alanine and sodium bicarbonate supplementation on cycling performance. Med Sci Sports Exerc. 2012;44(8):1545–1551. PMID: 22158262.
- Álvares TS, Meirelles CM, Bhambhani YN, et al. L-arginine as a potential ergogenic aid in healthy subjects. Sports Med. 2011;41(3):233–248. PMID: 22260513.
- Wolfe RR. Branched-chain amino acids and muscle protein synthesis in humans: myth or reality? J Int Soc Sports Nutr. 2017;14:30. PMID: 28852372.
- Cohen PA, Travis JC, Venhuis BJ. A methamphetamine analog (N,α-diethyl-phenylethylamine) identified in a mainstream dietary supplement. Drug Test Anal. 2014;6(7-8):805–807. PMID: 24176010.
- Sleivert G, Burke V, Palmer C, et al. The effects of deer antler velvet extract or powder supplementation on aerobic power, erythropoiesis, and muscular strength and endurance characteristics. Int J Sport Nutr Exerc Metab. 2003;13(3):251–265. PMID: 14620794.