The Supplement Evidence Hierarchy: Where Creatine Ranks

The global dietary supplement market exceeds $170 billion annually. It contains thousands of products making performance, recovery, and body composition claims. The majority of those claims are either unsupported by human research, supported only by industry-funded studies of questionable quality, or extrapolated from petri dishes and rodents to humans without verification.

This article applies a systematic evidence framework to the most commonly used sports supplements, ranking them by the strength, consistency, and quality of available peer-reviewed evidence. The goal is not to sell you on any product, but to provide the same evaluative framework that sports nutrition researchers use when they are asked what actually works.

The Ranking Framework

Each supplement is evaluated on five criteria drawn from evidence-based medicine principles:

1. Volume of evidence: How many randomized controlled trials (RCTs) exist in humans?
2. Meta-analytic confirmation: Have systematic reviews and meta-analyses confirmed the findings?
3. Consensus recognition: Have scientific bodies (ISSN, ACSM, IOC) issued position statements?
4. Mechanism clarity: Is the physiological mechanism well-characterized?
5. Consistency: Are results consistent across studies, populations, and training contexts?

Tier 1: Unambiguous Evidence

Creatine Monohydrate

Creatine monohydrate is the most extensively researched sports supplement in history. The International Society of Sports Nutrition position stand (Kreider et al., 2017) reviewed over 500 peer-reviewed studies and concluded that it is the most effective ergogenic nutritional supplement available for increasing high-intensity exercise capacity and lean body mass during training.

The mechanism is unambiguous: creatine supplementation increases intramuscular phosphocreatine stores by 20 to 40%, enhancing ATP resynthesis during maximal efforts. Meta-analyses consistently report 5 to 15% improvements in maximal strength and power, 1 to 2 kg additional lean mass gain over training cycles, and 10 to 20% increases in total work capacity during repeated high-intensity bouts.

Safety data spanning up to five years of continuous use shows no adverse effects on renal, hepatic, or cardiovascular function in healthy individuals. The cost is approximately $0.03 per gram, making it the most cost-effective supplement available.

For detailed mechanism explanations, see our How Creatine Works and Creatine and ATP Resynthesis articles.

Caffeine

Caffeine is the only other supplement that approaches creatine's evidence level, though the two operate through entirely different mechanisms. The ISSN position stand on caffeine (Guest et al., 2021) confirms significant ergogenic effects on endurance performance (2 to 4% improvement in time trials), muscular strength and power, and cognitive function during exercise.

Caffeine works acutely through adenosine receptor antagonism, enhanced catecholamine release, and altered pain perception. Unlike creatine, caffeine's effects diminish with habitual use, and genetic variation in CYP1A2 enzyme activity creates substantial inter-individual differences in response.

Tier 2: Strong Evidence with Narrower Applications

Beta-Alanine

Beta-alanine supplementation increases intramuscular carnosine concentrations by 40 to 80%, buffering hydrogen ions during sustained high-intensity exercise. Meta-analyses (Hobson et al., 2012; Saunders et al., 2017) confirm a median exercise capacity improvement of approximately 2.85% for efforts lasting 60 to 240 seconds. The ISSN issued a dedicated position stand (Trexler et al., 2015).

See Creatine vs. Beta-Alanine for the full comparison.

Dietary Nitrate (Beetroot Juice)

Concentrated beetroot juice provides dietary nitrate, which is reduced to nitric oxide, improving exercise economy. Jones et al. (2018) confirmed consistent benefits for moderate-intensity endurance exercise, particularly in recreationally active populations. Effects are attenuated in elite athletes.

Protein Supplements

Protein powder is a macronutrient supplement that helps individuals meet daily protein targets of 1.6 to 2.2 g/kg/day (Morton et al., 2018). It has no special properties beyond its amino acid content. Whole food protein sources are equally effective when total daily intake is equated.

Tier 3: Moderate Evidence

Citrulline Malate

May enhance nitric oxide production and ammonia clearance. Several RCTs show improved high-repetition resistance exercise performance, though results are inconsistent. See Creatine vs. Citrulline.

HMB (Beta-Hydroxy Beta-Methylbutyrate)

A metabolite of leucine with evidence for reducing muscle protein breakdown, particularly during caloric restriction. Replication concerns persist after controversial 2014 findings. See Creatine vs. HMB.

Ashwagandha

Several RCTs showing improvements in testosterone, strength, and recovery (Wankhede et al., 2015). Evidence is promising but limited. See Creatine vs. Ashwagandha.

Tier 4: Weak or Insufficient Evidence

BCAAs

Wolfe (2017) concluded there is no credible evidence that BCAAs alone stimulate muscle protein synthesis in individuals consuming adequate protein. See Creatine vs. BCAAs.

Glutamine

Human exercise studies consistently fail to show meaningful benefits for healthy athletes. See Creatine vs. Glutamine.

L-Carnitine

Oral supplementation does not meaningfully increase intramuscular carnitine concentrations (Wall et al., 2011). Fat-loss claims are not supported. See Creatine vs. L-Carnitine.

Tier 5: No Credible Evidence

Turkesterone

Social media popularity, no human clinical trials. See Creatine vs. Turkesterone.

Testosterone Boosters

Tribulus terrestris does not increase testosterone in humans (Neychev & Mitev, 2005). D-aspartic acid and fenugreek show equivocal results at best.

The Complete Hierarchy Table

Practical Recommendations

The minimum effective supplement stack for most exercising adults consists of creatine monohydrate (3-5 g/day), adequate protein from food, and caffeine if desired. Total cost: approximately $15 to $30 per month. This covers the only two Tier 1 ergogenic supplements plus the primary macronutrient requirement for training adaptation.

Beta-alanine may be worth adding for athletes competing in 1 to 4 minute events. Vitamin D supplementation is warranted when deficiency is documented. Beyond these specific situations, additional supplements provide diminishing returns that approach zero for most people.

For more comparisons, explore our full supplement comparison series, including creatine vs. protein, creatine vs. pre-workout, and evidence-based stacking protocols.