Moore · Nutrients 2023 · double-blind randomized placebo-controlled crossover trial · n=30

A Randomized Controlled Trial of Changes in Fluid Distribution across Menstrual Phases with Creatine Supplementation.

Level 2 - randomized trial

Individual randomized, double-blind, placebo-controlled crossover trial

PubMed 36678300 · doi:10.3390/nu15020429 · record verified 2026-08-26

What was done

Thirty moderately active females (either naturally menstruating or using hormonal contraceptives) were randomized in a double-blind, placebo-controlled crossover trial to creatine monohydrate loading (4 × 5 g/day for 5 days; n = 15) or non-caloric placebo (n = 15). Body mass, total body water (TBW), extracellular fluid (ECF), and intracellular fluid (ICF) were measured before and after supplementation in randomized order during the follicular and luteal phases using bioelectrical impedance spectroscopy, with acute hydration status and salivary estrogen used as covariates.

What was found

Body mass changes did not differ significantly between groups across the cycle ([PL - Cr] Δ 0.40 ± 0.50 kg; p = 0.427) or between menstrual phases ([FP - LP] Δ 0.31 ± 0.48 kg; p = 0.528). Baseline fluid markers did not differ at the pre-supplementation/follicular phase time point (TBW p = 0.802, ECF p = 0.373, ICF p = 0.795), and no differences appeared between naturally menstruating women and contraceptive users (p > 0.05). Following luteal phase supplementation, creatine caused significant increases across all fluid compartments compared to placebo: TBW (Cr: Δ 0.83 ± 0.38 L vs. PL: Δ -0.62 ± 0.38 L; p = 0.021), ECF (Cr: Δ 0.46 ± 0.15 L vs. PL: Δ -0.19 ± 0.15 L; p = 0.013), and ICF (Cr: Δ 0.74 ± 0.23 L vs. PL: Δ -0.02 ± 0.23 L; p = 0.041).

Why it matters

Creatine loading induces phase-dependent fluid shifts in females, expanding intra- and extracellular water compartments specifically during the luteal phase without causing the acute body mass increases commonly reported.

Limits

The study had a small sample size (n = 30 total, split across contraceptive statuses). Fluid distribution was estimated using bioelectrical impedance spectroscopy rather than gold-standard tracer dilution, and effects were evaluated only following acute 5-day loading without long-term maintenance or performance data.