Researchers combined results from 11 studies comparing two types of folate supplements for women planning to get pregnant. They found that the active form of folate (called methylfolate) may be more effective than regular folic acid at building up folate levels in the body and reducing birth defects. Women taking active folate had higher folate levels in their blood and fewer pregnancy complications. However, scientists say more research is needed to confirm these findings, especially studies that follow women for longer periods and track actual pregnancy outcomes.

The Quick Take

  • What they studied: Whether the active form of folate (methylfolate) works better than regular folic acid supplements for women of childbearing age
  • Who participated: 11 different research studies involving women of childbearing age, though the exact total number of women wasn’t specified in the summary
  • Key finding: Active folate supplements appeared to increase folate levels in the blood more effectively than regular folic acid and may reduce pregnancy complications in women who had previous miscarriages or birth defects
  • What it means for you: If you’re planning to get pregnant or have had pregnancy problems before, active folate (methylfolate) may be worth discussing with your doctor as an alternative to regular folic acid, though more research is still needed to be completely certain

The Research Details

This was a systematic review and meta-analysis, which means researchers searched multiple medical databases for all published studies comparing active folate to regular folic acid in women of childbearing age. They found 11 randomized controlled trials—the gold standard type of study where some women randomly received active folate and others received regular folic acid. The researchers then combined the results from all these studies to see if there were clear patterns.

The researchers looked at several important measurements: folate levels in the blood, folate stored in red blood cells, leftover folic acid that the body couldn’t use, pregnancy rates, and pregnancy complications. They used statistical methods to combine results from different studies and determine if the differences were meaningful or just due to chance.

This approach is important because individual studies can sometimes give different results due to chance or small sample sizes. By combining multiple studies together, researchers can see the bigger picture and determine if a finding is real and consistent. This type of analysis is especially valuable when deciding which supplement might be better for women’s health.

The researchers noted that the quality of the individual studies varied, and most studies were relatively short-term. The studies that showed the strongest benefits used doses of 0.4 mg or higher and lasted at least 12 weeks. Because the studies were limited in quality and duration, the researchers emphasized that more high-quality, long-term studies are needed before making definitive recommendations.

What the Results Show

Active folate supplements appeared to increase folate levels in the blood more effectively than regular folic acid (the difference was statistically significant). Similarly, active folate was better at building up folate stored in red blood cells, which is important because this storage form indicates long-term folate status. Importantly, active folate supplements resulted in much less leftover, unmetabolized folic acid in the body—meaning the body was using the supplement more efficiently.

For women who had experienced previous pregnancy problems, active folate supplementation appeared to increase the chances of becoming pregnant and reduce the risk of adverse pregnancy outcomes like miscarriage or birth defects. These findings were statistically significant, meaning they were unlikely to be due to chance alone.

However, the studies found no significant differences between active folate and regular folic acid in other blood markers like homocysteine, vitamin B12, and betaine levels. This suggests that while active folate is absorbed and used differently, it doesn’t necessarily change these other related nutrients.

Subgroup analysis (looking at specific groups of studies) revealed that the benefits of active folate were most pronounced when the dose was 0.4 mg or higher, when women took it for at least 12 weeks, and when the comparison was between active folate and an equal amount of regular folic acid. This suggests that dosage and duration of supplementation matter for seeing benefits.

This research builds on existing knowledge that folate is crucial for preventing neural tube defects (birth defects affecting the brain and spine) and supporting healthy pregnancy. Previous research established that regular folic acid supplementation is important, but some women don’t convert regular folic acid efficiently into the active form their bodies can use. This study suggests that providing the active form directly may be more effective for these women, though the research is still emerging.

The main limitations are that the individual studies included in this analysis varied in quality, and most were relatively short in duration. The researchers didn’t have information on the total number of women across all studies. Additionally, while the studies measured folate levels and some pregnancy outcomes, more research specifically tracking actual pregnancies and birth outcomes is needed. The studies also didn’t provide enough information about potential side effects or safety concerns with long-term use.

The Bottom Line

If you’re a woman of childbearing age planning pregnancy or have had previous pregnancy complications, discuss with your healthcare provider whether active folate (methylfolate) supplementation might be beneficial for you. The evidence suggests it may be more effective than regular folic acid, particularly at doses of 0.4 mg or higher taken for at least 12 weeks. However, confidence in these recommendations is moderate because more research is still needed. Always consult your doctor before starting any supplement, especially if you’re pregnant or planning to become pregnant.

This research is most relevant for women planning to get pregnant, women with a history of miscarriage or birth defects, and women who may have difficulty converting regular folic acid into its active form. Women already taking regular folic acid supplements should not stop without consulting their doctor. This research is less immediately relevant for men or women not of childbearing age, though folate is important for everyone’s health.

Based on the studies reviewed, folate levels in the blood can increase within weeks of starting supplementation, but building up adequate stores in red blood cells typically takes 8-12 weeks or longer. If you’re trying to become pregnant, it’s ideal to start folate supplementation at least 3 months before conception to ensure adequate levels are established.

Want to Apply This Research?

  • Track daily active folate supplementation intake (dose and time taken) and note any pregnancy-related symptoms or menstrual cycle changes. Users can log the specific dose (e.g., 0.4 mg, 0.8 mg) and set reminders for consistent daily intake.
  • Set a daily reminder to take active folate supplement at the same time each day (such as with breakfast) to build a consistent habit. If planning pregnancy, start supplementation at least 3 months before attempting conception and maintain consistent intake.
  • Track supplementation adherence over 12+ weeks, monitor any side effects or changes in energy levels, and note menstrual cycle regularity if applicable. Users can set monthly check-in reminders to assess consistency and discuss results with their healthcare provider at regular appointments.

This research summary is for educational purposes only and should not replace professional medical advice. Folate supplementation is especially important for women planning pregnancy or who are pregnant, but individual needs vary. Before starting any new supplement, including active folate, consult with your healthcare provider or obstetrician, particularly if you are pregnant, breastfeeding, taking medications, or have existing health conditions. This analysis is based on current research, but more studies are needed to fully establish the superiority of active folate over regular folic acid. Your doctor can help determine the best supplementation strategy for your individual circumstances.