A creatine-precursor supplement called guanidinoacetic acid (GAA) helped pregnant sheep carrying twins maintain better nutrition and body fat during late pregnancy, according to research reviewed by Gram Research analysis. However, the supplement slowed the development of blood vessels connecting mother to babies, suggesting the dosage may need adjustment to balance maternal health with proper fetal development.

Researchers studied whether a creatine-building supplement called guanidinoacetic acid (GAA) could help pregnant sheep carrying twins stay healthier during late pregnancy. According to Gram Research analysis, ewes that received the supplement showed better nutrition levels and maintained more body fat, but their blood vessels to the babies developed more slowly than expected. The study suggests that while GAA supplementation appears safe and effective for twin pregnancies in sheep, the dosage may need careful adjustment to balance the mother’s health with proper fetal development.

Key Statistics

A 2026 study of 15 twin-bearing ewes found that dietary supplementation with guanidinoacetic acid increased maternal blood levels of albumin, globulin, glucose, and cholesterol while reducing the loss of body fat during late pregnancy.

In the same 2026 research, ewes receiving guanidinoacetic acid supplementation showed reduced development of the uterine artery, umbilical blood vessels, and placental structures, with lower fetal heart rates compared to the control group.

A 2026 analysis of placental tissue in supplemented ewes revealed decreased expression of blood vessel growth genes (FGF2 and FLT1) and increased expression of an anti-growth gene (ODC1), explaining the slower vascular development observed.

The Quick Take

  • What they studied: Whether adding a creatine precursor (GAA) to the diet of pregnant sheep carrying twins improves their health and their babies’ development
  • Who participated: 15 pregnant ewes carrying twin lambs, split into two groups: 8 receiving normal feed and 7 receiving feed supplemented with guanidinoacetic acid from day 100 of pregnancy until birth
  • Key finding: Ewes receiving GAA supplementation maintained better nutrition levels and body fat, but their babies’ blood vessels developed more slowly than in the control group
  • What it means for you: For livestock farmers, GAA supplementation may help pregnant sheep carrying multiples stay healthier, but the dose needs careful adjustment to ensure babies develop properly. This research is specific to sheep and doesn’t directly apply to human pregnancy.

The Research Details

Researchers divided 15 pregnant ewes into two groups during the final months of pregnancy. One group ate standard feed, while the other group’s feed was supplemented with 0.9 grams per kilogram of guanidinoacetic acid (GAA), a natural compound that helps the body make creatine. The researchers measured changes in the mothers’ body composition, blood chemistry, and the development of blood vessels connecting mother to babies. They also examined genes involved in creatine production and blood vessel growth in the placenta and fetal tissues.

This type of study is called a controlled experiment because it compares two similar groups with one key difference—the supplement. By measuring many different outcomes, the researchers could see how GAA affected multiple aspects of pregnancy health. The study focused on late pregnancy (from day 100 until birth) because this is when nutritional demands are highest and when problems are most likely to occur.

Twin pregnancies in sheep create extra stress on the mother’s body because she must support two developing babies instead of one. This increases her need for nutrients and energy, and can lead to serious health problems like metabolic disease. Understanding how supplements like GAA affect both mother and babies is important for keeping pregnant sheep healthy and ensuring lambs are born strong. This research helps farmers make informed decisions about nutrition during high-risk pregnancies.

This study was published in a peer-reviewed scientific journal, meaning other experts reviewed the work before publication. However, the sample size is relatively small (only 15 ewes), which means results should be confirmed with larger studies. The research was conducted in a controlled setting with careful measurement of multiple outcomes, which strengthens confidence in the findings. The study is specific to sheep, so results may not apply to other animals or humans.

What the Results Show

Ewes receiving GAA supplementation showed several positive changes in their own health. Their blood levels of important proteins (albumin and globulin), glucose, and cholesterol all increased, suggesting better overall nutrition. More importantly, these supplemented ewes maintained thicker layers of fat around their loins and kidneys compared to the control group, meaning they didn’t lose as much body condition during pregnancy.

However, the supplement had unexpected effects on fetal development. The babies’ blood vessels developed more slowly in the supplemented group. Specifically, the uterine artery (which carries blood to the uterus), the umbilical blood vessels (which connect baby to placenta), and the placental structures all showed reduced growth. The fetal heart rate was also lower in the supplemented group. These changes suggest that while the mother’s nutrition improved, the babies’ development may have been slowed.

At the genetic level, researchers found that GAA supplementation changed how certain genes were expressed in the placenta. Genes involved in blood vessel growth (FGF2 and FLT1) were less active in the supplemented group, while a gene that prevents excessive blood vessel growth (ODC1) was more active. Additionally, genes involved in creatine regulation showed different patterns: GAMT expression decreased while CKM expression increased. These genetic changes help explain why blood vessel development was slower in the supplemented group.

Previous research has shown that creatine is important during pregnancy and helps support fetal development. However, most studies focused on single pregnancies or didn’t examine the effects of creatine precursors like GAA. This study is among the first to specifically investigate how GAA affects twin pregnancies in sheep. The finding that supplementation improved maternal nutrition but slowed fetal vascular development is somewhat surprising and suggests that the relationship between creatine and pregnancy is more complex than previously understood.

The study included only 15 ewes, which is a small number for drawing firm conclusions. Results from such small studies may not hold true in larger populations. The research was conducted in sheep, so findings may not apply to other animals or humans. The study only examined one dose of GAA (0.9 g/kg), so it’s unclear whether different doses might produce different results. The researchers did not follow the lambs after birth to see if slower blood vessel development affected their health or survival. Additionally, the study did not measure all possible markers of fetal health, so some effects may have been missed.

The Bottom Line

For sheep farmers managing twin pregnancies, GAA supplementation appears safe and may help maintain maternal nutrition and body condition. However, the current evidence suggests the standard dose may slow fetal blood vessel development, so dosage should be carefully adjusted. Moderate confidence: This recommendation is based on a small controlled study in sheep and should be confirmed with larger trials before widespread use.

Sheep and goat farmers managing pregnant animals carrying multiples should pay attention to this research. Veterinarians advising on livestock nutrition may find this useful. This research does not apply to human pregnancy—pregnant women should not use this information to make supplement decisions. Pet owners with pregnant animals should consult their veterinarian before considering any supplements.

Changes in maternal nutrition and body composition appeared within weeks of starting supplementation. However, effects on fetal development took longer to become apparent and were measured at the end of pregnancy (around day 100-145 of gestation). Farmers would need to plan supplementation well in advance of breeding to see benefits during pregnancy.

Frequently Asked Questions

Does creatine supplementation help pregnant animals carry twins safely?

A 2026 study found that guanidinoacetic acid (a creatine precursor) improved maternal nutrition and body condition in pregnant ewes carrying twins, but slowed fetal blood vessel development. Benefits and risks must be balanced, and dosage requires careful adjustment.

What is guanidinoacetic acid and how does it work in pregnancy?

Guanidinoacetic acid (GAA) is a natural compound that helps the body produce creatine, which provides energy to cells. During pregnancy, it may improve maternal nutrition, but research shows it can also slow fetal vascular development, suggesting complex effects on pregnancy metabolism.

Can I use creatine supplements if I’m pregnant with twins?

This research was conducted in sheep, not humans. Pregnant women should not use this information to make supplement decisions. Always consult your doctor before taking any supplements during pregnancy, as effects may differ significantly from animal studies.

Why did the babies develop slower blood vessels with the supplement?

The supplement changed gene expression in the placenta, reducing activity of genes that promote blood vessel growth (FGF2, FLT1) while increasing an anti-growth gene (ODC1). This suggests the supplement redirected the body’s metabolic effort toward maternal nutrition at the expense of fetal vascular development.

Is guanidinoacetic acid safe for pregnant livestock?

A 2026 study found GAA supplementation was tolerated well by pregnant ewes and improved maternal health markers. However, the slower fetal blood vessel development raises questions about optimal dosage. Veterinary consultation is recommended before use in livestock.

Want to Apply This Research?

  • For livestock managers using an app: Track maternal body condition score (on a 1-5 scale) weekly during late pregnancy, and record blood work results (glucose, albumin, cholesterol levels) monthly to monitor nutritional status when using GAA supplementation.
  • If using GAA supplementation, adjust feeding protocols to include the supplement starting at day 100 of pregnancy, monitor the pregnant animal’s weight and body condition twice weekly, and schedule ultrasound checks to verify normal fetal blood vessel development.
  • Establish a baseline measurement of maternal body condition and blood chemistry before starting supplementation. Continue weekly assessments of body condition and monthly blood work throughout late pregnancy. After lambing, track lamb birth weight, vigor, and early growth to determine if slower fetal vascular development affected outcomes. Use this data to adjust dosage for future pregnancies.

This research was conducted in sheep and does not apply to human pregnancy. Pregnant women should not use this information to make supplement decisions and must consult their healthcare provider before taking any supplements. Livestock farmers should consult with a veterinarian before implementing any new supplementation protocols. This article summarizes research findings and is not medical or veterinary advice. Individual responses to supplementation may vary, and dosage adjustments should only be made under professional guidance.

This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.

Source: Creatine-precursor exposure in ewe twin pregnancy directs metabolic effort and reworks the maternal-fetal vascular system, involving genetic markers that modulate the creatine pathway.Frontiers in veterinary science (2026). PubMed 42494953 | DOI