Creatine Stacking: Evidence-Based Supplement Combinations

Creatine monohydrate is the foundation of evidence-based sports supplementation. The question that naturally follows is: what else should you stack with it? The answer depends on your goals, training style, and budget. Some combinations have direct research support. Others are theoretically rational based on non-overlapping mechanisms. And some commonly marketed stacks add cost without adding benefit. This guide evaluates each combination based on the quality and quantity of available evidence.

The Evidence Tier System

Each creatine stacking combination is rated on the following scale:

• Tier A: Strong Evidence — Multiple RCTs, meta-analyses, and/or position statements directly supporting the combination.
• Tier B: Moderate Evidence — Some RCT support and strong mechanistic rationale. Individual components well-supported even if combination studies are limited.
• Tier C: Theoretical/Weak — Mechanistic rationale exists but direct combination evidence is minimal or inconsistent.
• Tier D: Not Recommended — No evidence of added benefit, or the additional component lacks independent evidence.

Tier A Stacks: Strong Evidence

Creatine + Protein

The most well-supported supplement stack in sports nutrition. Cribb et al. (2007) directly compared creatine, protein, and the combination, finding the combination group achieved the greatest gains in lean mass, strength, and muscle fiber cross-sectional area. Burke et al. (2001) showed creatine plus protein outperformed creatine plus carbohydrate for lean tissue gains. The mechanisms are entirely independent (ATP regeneration vs. amino acid supply), and the combination addresses both the performance and recovery sides of the training equation. Cost: $40 to $75/month combined.

Creatine + Beta-Alanine

Hoffman et al. (2006) found that creatine plus beta-alanine produced greater improvements in lean mass and body composition than either alone in strength/power athletes over 10 weeks. The mechanistic rationale is strong: creatine enhances the phosphocreatine system (dominant in 0 to 30 second efforts), while beta-alanine enhances the carnosine buffering system (dominant in 60 to 240 second efforts). Together they cover both major anaerobic energy systems. The ISSN has position stands supporting each individually. Cost: $25 to $40/month combined.

Creatine + Caffeine

Both are independently well-supported ergogenic aids. A 1996 study by Vandenberghe raised concerns about caffeine blunting creatine's effects, but subsequent research has not consistently confirmed this interaction. Trexler and Smith-Ryan (2015) concluded the evidence does not support a clinically meaningful negative interaction when both are consumed chronically. The mechanisms are different (creatine: ATP regeneration; caffeine: adenosine receptor antagonism, reduced perceived exertion, enhanced neural drive). Cost: $12 to $17/month combined.

Tier B Stacks: Moderate Evidence

Creatine + Citrulline Malate

No direct combination studies, but each has independent evidence. Creatine targets the phosphocreatine system while citrulline malate targets NO-mediated vasodilation and potentially aerobic ATP resynthesis via the malate component. The theoretical case for additive benefits is sound, particularly for high-volume resistance training. Both are commonly included in pre-workout formulas, though citrulline is frequently underdosed in commercial products. Take creatine daily (3 to 5 g), citrulline malate pre-workout (6 to 8 g). Cost: $25 to $40/month combined.

Creatine + HMB (Specific Populations)

Jowko et al. (2001) showed additive benefits of creatine and HMB in untrained males. However, this combination is most relevant for novice trainees, elderly populations at risk of sarcopenia, and individuals in catabolic states. For trained individuals with adequate protein intake, HMB adds minimal value. Cost: $35 to $60/month combined, making it expensive relative to the marginal benefit for most users.

Creatine + Protein + Beta-Alanine (Triple Stack)

Combining the top three evidence-based supplements. No single study has tested this exact triple combination, but each pairwise combination has support, and the three mechanisms are entirely non-overlapping. This represents the most comprehensive evidence-based ergogenic stack for an athlete doing both short-burst and sustained high-intensity training. Cost: $45 to $65/month.

Tier C Stacks: Theoretical but Limited Evidence

Creatine + Ashwagandha

Ashwagandha (Withania somnifera) has some evidence for improving strength and recovery, with Wankhede et al. (2015) showing increases in bench press and leg extension strength versus placebo. The mechanism (likely cortisol modulation and adaptogenic effects) is different from creatine's. However, the ashwagandha evidence base is smaller and less consistent than creatine's, and no direct combination study exists. A reasonable speculative stack but not one with strong direct evidence.

Creatine + Betaine (Trimethylglycine)

Betaine is an osmolyte and methyl donor with some evidence for improving power output and body composition. Cholewa et al. (2013) found betaine supplementation improved body composition during resistance training. The mechanism (osmolyte, methyl donation) differs from creatine. However, the betaine literature is still mixed, with some null findings. Not harmful to combine, but the added value is uncertain.

Creatine + Omega-3 Fatty Acids

Lewis et al. (2015) found that omega-3 fatty acid supplementation enhanced the sensitivity of muscle protein synthesis to hyperaminoacidemia in older adults. The combination with creatine targets different pathways (energy metabolism vs. inflammation/membrane fluidity/MPS sensitivity). No direct combination study, but both are independently supported for health and performance. Omega-3s are more of a health supplement than an ergogenic aid.

Tier D Stacks: Not Recommended

Creatine + BCAAs

BCAAs provide no additional benefit beyond adequate total protein intake in healthy individuals (Wolfe, 2017). Since a well-designed supplementation plan already includes sufficient protein (via food and/or protein powder), adding BCAAs is redundant. Money spent on BCAAs is better allocated to food or protein powder.

Creatine + Glutamine

Glutamine supplementation has failed to demonstrate benefits for muscle growth, strength, or recovery in healthy, well-nourished individuals performing resistance training (Gleeson, 2008). It may have a narrow use in critical care or extreme endurance contexts, but for the typical resistance trainee, it adds nothing to a creatine regimen.

Creatine + Turkesterone

Turkesterone (an ecdysteroid) lacks rigorous human evidence for any muscle-building effect. The most relevant human study on ecdysteroids (Isenmann et al., 2019) found no significant effect on muscle mass or strength. Adding an unproven supplement to a proven one does not create a better stack.

Stack Summary Table

Verdict

Start with creatine. If you have additional budget, add protein powder (if you do not meet daily protein needs through food), then caffeine (if you train in a context where a stimulant is beneficial), then beta-alanine (if your training involves sustained high-intensity work). These three additions to creatine represent the four-supplement stack with the strongest combined evidence base in sports nutrition.

Everything beyond that tier enters territory of diminishing returns, increased cost, and uncertain benefit. The supplement industry profits from complexity, but the evidence favors simplicity. The four compounds with the strongest evidence (creatine, protein, caffeine, beta-alanine) are also among the cheapest and most accessible. That is not a coincidence; it is a reflection of how well they have been studied and how reliably they work.