For years, mums have been told to take folic acid to support their baby’s development. It’s been one of public health’s biggest success stories, helping prevent serious birth defects. But new research suggests there might be more to the picture.

In this episode, Dr Renee White explores an Australian study that questions whether excess folic acid could be contributing to rising rates of gestational diabetes. Renee breaks down the findings, what they mean for pregnant women, and why personalised care matters when it comes to supplements and pregnancy health.

You’ll hear about:

• How folic acid fortification changed pregnancy outcomes worldwide
• What researchers found about folate levels and gestational diabetes risk
• The role genetics, like MTHFR variants, may play in folic acid metabolism
• Why a “one size fits all” approach to supplementation might need rethinking
• What to discuss with your healthcare provider before making changes

This episode reminds us that science evolves, and understanding the evidence helps us make informed choices. Mamas stay curious, ask questions, and keep working with your healthcare team to find what’s right for you.

Resources & Links

📲 Connect with Renee on Instagram: @fillyourcup_

🌐 Learn more about Dr Renee White and explore Fill Your Cup Doula services

🍪 Treat yourself with our Chocolate + Goji lactation cookies

If you found this episode helpful, share it with a friend or tag @fillyourcup_ on Instagram. And don’t forget to follow The Science of Motherhood so you never miss an episode.

Disclaimer:

The information on this podcast presented by Fill Your Cup is not a substitute for independent professional advice. Nothing contained in this episode is intended to be used as medical advice and it is not intended to be used to diagnose, treat, cure or prevent any disease, nor should it be used for therapeutic purposes or as a substitute for your own health professional's advice.

[00:00:30] Dr. Renee White: Hello and welcome to episode 197 of The Science of Motherhood. I'm your host, Dr. Renee White. Thanks so much for joining me today. I just do wanna do a quick shout out if you are loving this [00:00:45] podcast, if you have shared any of our episodes and as we approach, uh, our big 200 episode, which is so, so exciting.

[00:01:21] Dr. Renee White: And it's not just me. We've got the beautiful Julia, who is my amazing virtual assistant and Jono, who has been [00:01:30] editing these podcasts for the past four years. So collectively thank you. Thanks guys, for continuing to have us in your ears. But yeah, it would, uh, mean the world to us. If you can just take five [00:01:45] seconds to hit five stars. That would be absolutely amazing.

[00:02:09] Dr. Renee White: Okay, this is very interesting. In today's episode, [00:02:15] we are going to be examining a study that challenges one of our most successful public health interventions, and we are talking about folic acid fortification. It's a policy that virtually eliminated, you know, neural tube [00:02:30] defects, but may have created an unexpected consequence.

[00:03:04] Dr. Renee White: So straight off the bat, let's look at the background and the context. Cause we always need to be mindful of this and to understand this study, we need to go all the way back to the [00:03:15] 1990s. Now researchers discovered that folic acid, which is a B vitamin. Could prevent neural tube defects. Note serious birth defects affecting the brain and spine, and the evidence was so [00:03:30] compelling that countries worldwide began fortifying foods and recommending supplements.

[00:04:04] Dr. Renee White: Gestational diabetes rates were climbing steeply. So from 2010 to 2022, gestational diabetes [00:04:15] increased from 5.6%. To 19.3% nationally. While some of this, you know, increase could be attributed to diagnostic changes in [00:04:30] 2015, the trend started earlier and continued after adjustments were made for this new kind of diagnostic change.

[00:05:23] Dr. Renee White: And so this gave them an unprecedented opportunity to examine whether the timing, [00:05:30] coincidence. Was more than just that. So let's look at the study design. We always need to look at that when we're analyzing research papers. So the researchers compared two cohorts, so two groups of people. The first one was called [00:05:45] Scope and they recruited 1,164 women between 2005 to 2008.

[00:06:23] Dr. Renee White: When we're testing things, we wanna keep the variables the same as as much as we [00:06:30] can. And then that one variable that we are testing, that's the one that's gonna be different. So this temporal comparison, time comparison design has both strengths and I guess significant limitations.

[00:07:09] Dr. Renee White: So serum folate reflects recent intake while red [00:07:15] cell folate indicates long-term stores. And so that's, I guess a more stable measure of folate status over months. And they also examined, which is, this is I think the [00:07:30] coolest part. They also examined placental hormones, specifically human placental lactogen and placental growth hormone variant.

[00:08:21] Dr. Renee White: But the folate changes were even more dramatic. So the red cell folate levels increased by [00:08:30] 259% nearly 58% of women in the post fortification group had folate levels above the normal clinical range. And this, uh, this, this, this wasn't just, uh, [00:08:45] like, you know, a modest increase. It represented a fundamental shift in population folate status, and the researchers found that women with excess folate had [00:09:00] 48% more gestational diabetes cases compared to those with normal levels.

[00:09:32] Dr. Renee White: So human placental lactogen was 12.8% higher and prolactin was 24.2% higher in women with folate excess. And these hormones, this is [00:09:45] the, this is the fascinating part, guys. These hormones regulate insulin sensitivity and glucose metabolism suggesting a potential biological pathway. And the [00:10:00] statistical modeling indicated that the combination of higher folate levels and the post fortification time period placed women at more than three fold increased risk of gestational diabetes.[00:10:15]

[00:10:45] Dr. Renee White: Now, genetic variants in this gene are extremely common, affecting 10 to 15% of the population in their more kind of severe forms, and up to 40% with milder variants. [00:11:00] So, to kind of put this into real world context, people with the MTHFR variants, they process folic acid very differently, and they may have a reduced [00:11:15] ability to convert that synthetic folic acid that we see in the fortified flours and breads and things like that into the active form, which is what the body.

[00:11:59] Dr. Renee White: Don't know. [00:12:00] Jury's out, right. Because in populations with mandatory fortification, women with certain MTHFR variants might accumulate high levels of unmetabolized folic acid, which some [00:12:15] research suggests could interfere with normal cellular processes. So, you know, the absence of this kind of analysis in the study means that we, we just, we just don't know right. Further, further work needs to be done.[00:12:30]

[00:12:49] Dr. Renee White: You know, numerous factors changed beyond folic acid, fortification, diagnostic practices, population demographics, so on and so forth. [00:13:00] The researchers adjusted for known confounders like age, BMI, ethnicity and and things like that. The second limitation, obviously, is the study's observational design. It can only demonstrate [00:13:15] association not causation okay.

[00:13:46] Dr. Renee White: And also the red cell folate data for the pre fortification comparison came from a separate cohort of 410 women, so not the scope study itself. [00:14:00] And so I guess, you know, while these samples were collected at the same time and hospital using identical methods, this kind of introduces another potential source of variability, right. So we need to acknowledge that.

[00:14:42] Dr. Renee White: So in countries with mandatory fortification, [00:14:45] this combination easily creates folate excess. And so I guess the study really raises an important question about our one size fits all approach with supplementation. You know, should we [00:15:00] be assessing individual folate status before recommending supplements?

[00:15:33] Dr. Renee White: We are absolutely not saying that, and neither are the researchers. The neural tube defect prevention benefits are well established and critical, so stopping [00:15:45] supplementation could lead to preventable birth defects. And instead, I guess the researchers are now suggesting we just need more nuanced approaches right.

[00:16:17] Dr. Renee White: This study opens several important research directions I think first of all, we need to replicate in other populations and with study designs, you know, prospective randomized trials, [00:16:30] we also need to have a genetic analysis. I think that's essential. Understanding how the MTHFR and other genetic variants modify that folate, metabolism, and diabetes risk could really [00:16:45] be quite interesting.

[00:17:16] Dr. Renee White: It challenges us right, to move beyond this whole kind of, you know, thick brush per, you know, population wide approaches towards more personalized strategies. You know, we are seeing that in cancer [00:17:30] treatment, you know, where genetics are being scanned and then depending on what your genetics are and your cancer and things like that, it's a real personalized approach.

[00:18:11] Dr. Renee White: So the goal isn't to abandon all [00:18:15] folic acid supplementation. Really what we're asking for, I think, out of this study is to optimize it. To preserve the remarkable success in preventing birth defects while, you know, minimizing any potential risks. [00:18:30] And that's the challenge for the researchers, clinicians, policy makers, really moving forward.

[00:19:06] Dr. Renee White: DM us, email us. I would love to take that on. We are gonna be doing that more and more in the future and we have got a fantastic [00:19:15] episode coming up, talking to an expert for exactly this reason. We had a DM from someone who was curious about something and we found an expert and we are going to answer a question.

[00:19:46] Dr. Renee White: You've just listened to another episode of The Science of Motherhood proudly presented by Fill Your Cup, Australia's first doula village.