Creatine During Pregnancy: Current Research and Unknowns

Creatine supplementation during pregnancy represents one of the genuinely uncertain areas in creatine research. Unlike kidney function or hair loss, where the evidence clearly supports safety, the pregnancy question involves a population that is largely excluded from supplement trials for ethical reasons. The research that does exist is provocative: animal studies suggest that maternal creatine supplementation may protect the developing fetal brain from birth-related oxygen deprivation. But translating animal findings to human recommendations requires human trials that are only beginning to emerge.

Why Creatine Matters During Fetal Development

The developing fetus has high energy demands, and the creatine-phosphocreatine system plays an important role in fetal metabolism. Creatine is synthesized by the fetus, but fetal synthesis capacity is limited, particularly in early development. The placenta transfers creatine from maternal blood to the fetus, supplementing fetal production.

During labor and delivery, the fetus may experience periods of reduced oxygen supply (hypoxia). The phosphocreatine system serves as an energy reserve that can buffer ATP demand during these hypoxic episodes, maintaining cellular function until oxygen supply is restored. A fetus with higher phosphocreatine reserves may be better equipped to tolerate birth-related hypoxia without sustaining organ damage, particularly brain injury.

This biological rationale has made maternal creatine supplementation a subject of serious investigation in perinatal medicine, primarily through the work of researchers in Australia.

The Ellery et al. Research Program

Stacey Ellery and colleagues at the Hudson Institute of Medical Research in Melbourne, Australia, have led the investigation into creatine and pregnancy. Their research program has progressed from animal models to human observational studies and early clinical work.

Ellery et al. (2020), publishing in Nutrients, provided a comprehensive review of the evidence for creatine as a potential intervention for fetal neuroprotection. Their review summarized the preclinical data, the biological rationale, and the current state of human research. Key findings from their review included evidence from animal models showing that maternal creatine supplementation reduced brain injury in offspring subjected to birth asphyxia, evidence that creatine crosses the placenta and contributes to fetal creatine pools, and the identification of a need for human clinical trials to establish safety and efficacy in pregnant populations.

The animal data is compelling. In spiny mouse models (chosen because their placental structure resembles human placentation), maternal creatine supplementation prior to induced birth asphyxia resulted in significantly less brain injury in offspring compared to non-supplemented controls. The protective effect was attributed to enhanced phosphocreatine reserves in the fetal brain, which maintained ATP levels during oxygen deprivation.

The Dickinson et al. Preclinical Data

Dickinson et al. (2014) published preclinical research examining the mechanisms of creatine-mediated neuroprotection in fetal development. Their work, published in the Journal of Clinical and Experimental Pharmacology and Physiology, examined creatine supplementation in animal models of birth asphyxia and demonstrated protective effects on multiple organ systems, not only the brain.

The protective effects extended to the diaphragm (respiratory function), kidneys, and other organs vulnerable to hypoxic-ischemic injury during complicated deliveries. This multi-organ protection is consistent with the role of phosphocreatine as a universal energy buffer: any organ with high energy demands can benefit from enhanced creatine stores during periods of compromised oxygen supply.

Human Observational Data

Observational studies have examined creatine levels in pregnant women and their relationship to pregnancy outcomes. Lower maternal creatine levels have been associated with lower birth weight in some studies. The fetal capacity for creatine synthesis increases throughout gestation but remains limited relative to postnatal capacity, suggesting that maternal supply is physiologically important during pregnancy.

Dietary creatine intake during pregnancy varies widely and depends on meat consumption. Vegetarian and vegan pregnant women have lower creatine intake from diet and may have lower creatine stores. Whether this dietary variation translates to differences in fetal outcomes is an active area of investigation.

Current State of Human Trials

As of this writing, human clinical trials of creatine supplementation during pregnancy are in early stages. The transition from animal models to human trials requires establishing safety in the pregnant population before efficacy can be assessed. This process is appropriately cautious, as any intervention during pregnancy carries potential risks to both mother and fetus that must be thoroughly evaluated.

The safety profile of creatine in non-pregnant populations is reassuring. Creatine is an endogenous compound already present in the body, synthesized naturally, and obtained through dietary sources. It is not a xenobiotic or pharmaceutical. These characteristics support its biological plausibility as a safe intervention during pregnancy, but plausibility is not evidence. Human pregnancy safety data is needed.

What We Do Not Know

Several critical questions remain unanswered:

Dosing during pregnancy. The optimal dose of creatine for maternal-fetal benefit has not been established in humans. The standard 3-5 g/day maintenance dose used in athletic populations may or may not be appropriate during pregnancy. Maternal physiology, blood volume expansion, renal function changes, and placental transfer dynamics all affect how creatine is distributed and metabolized during pregnancy.

Timing. When during pregnancy creatine supplementation should begin and end has not been determined. The fetal neuroprotection hypothesis suggests that supplementation in late pregnancy (when the risk of birth complications is highest) would be most relevant. However, creatine stores take weeks to saturate, so earlier initiation might be necessary to ensure adequate fetal reserves at delivery.

Safety for the developing fetus. While animal studies have shown no adverse effects on fetal development from maternal creatine supplementation, human fetal safety data is limited. The developing human brain, endocrine system, and other organs may respond differently than animal models.

Interactions with pregnancy complications. How creatine supplementation interacts with gestational diabetes, preeclampsia, intrauterine growth restriction, and other pregnancy complications is unknown. These conditions alter maternal metabolism in ways that could affect creatine dynamics.

Current Recommendations

No major medical organization currently recommends creatine supplementation during pregnancy. This is not because evidence suggests it is harmful. It is because insufficient evidence exists to make a positive recommendation. The standard of evidence for recommending interventions during pregnancy is appropriately higher than for the general population.

Women who were taking creatine before becoming pregnant face a practical decision. Stopping supplementation poses no known risk to the pregnancy (creatine stores naturally deplete over 4-6 weeks). Continuing supplementation means using a supplement that has not been specifically evaluated for pregnancy safety in human trials, even though the available evidence does not suggest harm.

This decision should be made in consultation with an obstetrician or maternal-fetal medicine specialist. The physician can weigh the individual patient's risk profile, the available evidence, and the patient's comfort with uncertainty.

Breastfeeding

Creatine is present in breast milk, reflecting the fact that it is a normal component of human physiology. The concentration of creatine in breast milk has been measured, and it contributes to the neonate's creatine supply during a period when endogenous synthesis capacity is still developing.

Whether supplemental creatine increases breast milk creatine concentration and whether this has any effect on the nursing infant are questions that have not been thoroughly studied. As with pregnancy, the biological plausibility of safety is strong (creatine is endogenous and present in breast milk at baseline), but specific supplementation data in breastfeeding women is lacking.

Summary

Creatine during pregnancy is a research frontier, not a settled question. Animal studies provide compelling evidence that maternal creatine supplementation may protect the fetal brain during birth-related oxygen deprivation. Human observational data supports the biological importance of maternal creatine supply to the developing fetus. However, human clinical trial data on the safety and efficacy of creatine supplementation during pregnancy is insufficient to support a recommendation for or against its use. Pregnant women considering creatine should consult their obstetrician and recognize that this decision involves genuine uncertainty that has not yet been resolved by the research.