Does a meat-free diet modify creatine homeostasis in pregnancy? A nested cohort study

Abstract Purpose Creatine is obtained through endogenous synthesis and meat-based dietary sources. This study investigated whether a meat-free diet alters maternal creatine homeostasis during pregnancy and whether creatine-related metabolites are associated with newborn growth. Methods This nested study included 24 non-meat eaters and 39 meat eaters from the Australian Creatine and Pregnancy Outcomes cohort. Dietary intake was assessed throughout pregnancy. Creatine, guanidinoacetate (GAA), creatinine and amino acids involved in creatine synthesis were measured in maternal plasma and urine, placental tissue and cord bloods. Mixed-effects models examined longitudinal metabolite concentrations and exploratory associations with newborn growth. Results Non-meat eaters had 30% lower maternal plasma creatine ( p = 0.001) and 55% lower urinary creatine concentrations ( p = 0.01) throughout pregnancy than meat eaters, whereas plasma GAA was higher at birth ( p = 0.03). No between-group differences in placental or cord-blood creatine were detected, although these analyses involved smaller subsets. Overall, higher maternal plasma creatine was associated with greater birth length (β0.020 cm; 95% CI 0.005 to 0.035; p = 0.01) and head circumference (β0.021 cm; 95% CI 0.010 to 0.031; p < 0.001). Higher plasma and urinary GAA were associated with smaller head circumference (plasma: β − 0.648 cm; 95% CI − 1.071 to − 0.226; p = 0.003; urine: β − 0.0042 cm; 95% CI − 0.0081 to − 0.0003; p = 0.04). However, no creatine- or GAA-by-dietary-group interactions remained significant after false discovery rate correction. Conclusion A meat-free diet was associated with substantially lower maternal creatine concentrations throughout pregnancy. Associations between maternal creatine-related metabolites and newborn growth require confirmation in larger prospective studies to clarify their clinical implications for maternal and newborn health. Trial registration number ACTRN12618001558213. The trial was registered on 13/09/2018.