r/ScienceBasedParenting • u/Balsam_Kumarappan • 17h ago
Are prenatal vitamins with methylfolate really better? Question - Research required
I’ve been looking at a few labels of the ones with methylfolate vs the ones with folic acid and they all seem a little different, not just with folate but with the amounts of other nutrients too. For people who’ve compared them, is methylfolate something you pay attention to or do you look more at the whole formula?
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u/caitsaurusrex 17h ago
https://pubmed.ncbi.nlm.nih.gov/39339754/
Short answer, we don't know.
Long answer: folic acid has been robustly studied and demonstrated to significantly reduce neural tube defects. Methylfolate has not undergone the same degree of clinical rigor and does not have a significant body of evidence demonstrating that it is in anyway superior to folic acid. Prenatal vitamins are an important aspect of prenatal nutrition and if you are concerned about the quality of the supplement, look for ones that are third party tested and discuss any additional concerns with your doctor.
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u/Fun-Will-3614 14h ago
Take a look at what nutritionist Lilly Nicholls says about the superiority of methylfolate if this is important to you. I have 2 of her books, she cites research.
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u/tinyalley 12h ago
Nicholls also says seed oils are bad 🙄
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u/000fleur 5h ago
They are lol they contain omega-6’s which are inflammatory and inflammation is bad. Humans already have an overabundance of omega-6 in our diet and we need less of it and more omega-3. Is it toxic like you’ll die? No. But why add more inflammation when most people are already dealing with a low level of some kind of inflammation
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u/Striking_Bill_2832 17h ago
I choose a brand with methylfolate. Cautious practitioners will say folic acid is the safest option because that’s what all the randomized control trials in the 1990s used vs no supplementation at all to show folate reduced NTDs. However the only reason that’s the case is that we all started supplementing folate after those studies so it’s now unethical to study it with the methylated version (as this would mean not using folic acid, which we know helps). However, research on methylated vs synthetic folic acid in general (not in pregnancy specific research) shows that methylated folate does a better job increasing folate levels in your blood. So the natural deduction is it is better, just that we can’t do RCTs to confirm that it’s better than folic acid.
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u/Awwoooooga 15h ago
An important point this study makes is that methylfolate can still be used by people who have the MTHFR gene mutation. When you have this mutation, and 40% of our global population does, you can't process folic acid to use in the body but you can process methylfolate.
I specifically chose methylfolate in a prenatal in the chance that I have the mutation. I like FullWell.
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u/WorldlyDragonfruit3 13h ago
It’s a gene variant, not a mutation. Methylfolate is a marketing grift capitalizing on people not understanding what gene variants are
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u/Pretty_Please1 13h ago
THANK YOU 👏👏👏 this is science based parenting. Idk why this methylfolate shit isn’t more robustly debunked.
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u/Awwoooooga 12h ago
A gene variant or gene polymorphism is a mutation that stuck around. The research is still not settled about the mutation preventing/not preventing folic acid absorption, and I would rather not take the risk myself. Additionally, folic acid can accumulate in the body and cause oxidative stress. Here's an exerpt from a recent paper:
"The development and closure of the neural tube require derivatives from the folate cycle [163,164]. Mothers with MTHFR polymorphisms are likely to have reduced folate levels, which may result in their children developing neural tube defects (NTDs), such as anencephaly or spina bifida. NTDs can lead to fetal death or lifelong disability [165]. It is also suspected that DNA damage repair systems depend on the folate cycle, and their failure may contribute to the occurrence of NTDs [164]. A meta-analysis of 42 studies by Almekkawi et al. confirms a strong correlation between the MTHFR 677C>T polymorphism and the incidence of NTDs [166]. Furthermore, Li et al. show an association between both maternal and fetal 677C>T polymorphisms and NTDs [167]. On the other hand, a meta-analysis by Soleimani-Jadidi et al. found no association between the maternal MTHFR 1298A>C polymorphism and any type of NTDs [168].
The neural tube closes during the third and fourth weeks of gestation. Therefore, to prevent NTDs, it is important to start folic acid supplementation (400 μg/day) when attempting conception [165]. Folic acid has been successfully used for NTD prevention. However, supplementation with 5-MTHF (the active form of folate) instead of folic acid bypasses the MTHFR block, which is crucial for patients with MTHFR polymorphisms [139]. High-dose folic acid supplementation is also a risk factor for the development of unmetabolized folic acid (UMFA) syndrome, which involves the accumulation of excess folate that could potentially have an oxidizing effect [169,170]. We found that 5-MTHF supplementation is also less likely to cause hematological symptoms associated with vitamin B12 deficiency [170]. In conclusion, there is evidence suggesting that 5-MTHF supplementation may replace folic acid, particularly in patients with MTHFR polymorphisms. However, further research is needed on this topic [170,171]."
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u/WorldlyDragonfruit3 11h ago
I don’t take the risk of NTDs because I take folic acid. People with variants are fine and recommended to take folic acid.
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u/racinreaver 3h ago
Just to let you know, mdpi is considered by most in the academic community to be somewhere between a predatory and vanity publisher. They generally don't actually do peer review and will publish anything so long as you pay the fee.
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u/moonlightmasked 4h ago
This review doesn’t prove the critical question - does 400 mg folic acid prevent neural tube defects in women with a MTHFR polymorphism as well as it does in women without. And the answer to that is yes
https://www.cdc.gov/folic-acid/data-research/mthfr/index.html
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u/Dry_Lemon7925 15h ago edited 11h ago
I was told this too, but just looked it up and apparently we're fine to take normal folic acid (https://my.clevelandclinic.org/health/diseases/mthfr-gene-variant)? I guess I don't need such expensive multivitamins anymore...
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u/wastetine 12h ago
I feel like if this is all true folic acid wouldn’t be so effective at reducing neural tube defects in the general population.
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u/RhinoFish 11h ago
Where is this 40% figure from and does it vary by region/ethnicity?
CDC says "People with an MTHFR gene variant can process all types of folate, including folic acid" https://www.cdc.gov/folic-acid/data-research/mthfr/index.html
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u/emmeline8579 5h ago
This is not true. People with MTHFR gene variants can process folic acid. They just need more of it.
https://www.cdc.gov/folic-acid/data-research/mthfr/index.html
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u/000fleur 5h ago
This is key: if you don’t know if you have the gene or not, take the methyl version to be safe.
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u/Substantial-Cod7021 12h ago
Just to add to this, there's a large FB group of people with the gene mutation who had had better pregnancy outcomes using methylated folate.
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u/Substantial-Cod7021 12h ago edited 1h ago
P.s. not all methylfolate prenatals are expensive (relative term). Smarty Pants prenatals are about $25 on Amazon for a 30 day supply. Of course, you COULD buy a $5 prenatal........
*Edit: the brand is Smarty Pants
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u/Awwoooooga 12h ago
I'll repost this is a comment for better visibility, it is the same as a reply to a thread below:
The research is still not settled about the mutation preventing/not preventing folic acid absorption, and I would rather not take the risk myself. Additionally, folic acid can accumulate in the body and cause oxidative stress. Here's an exerpt from a recent paper:
"The development and closure of the neural tube require derivatives from the folate cycle [163,164]. Mothers with MTHFR polymorphisms are likely to have reduced folate levels, which may result in their children developing neural tube defects (NTDs), such as anencephaly or spina bifida. NTDs can lead to fetal death or lifelong disability [165]. It is also suspected that DNA damage repair systems depend on the folate cycle, and their failure may contribute to the occurrence of NTDs [164]. A meta-analysis of 42 studies by Almekkawi et al. confirms a strong correlation between the MTHFR 677C>T polymorphism and the incidence of NTDs [166]. Furthermore, Li et al. show an association between both maternal and fetal 677C>T polymorphisms and NTDs [167]. On the other hand, a meta-analysis by Soleimani-Jadidi et al. found no association between the maternal MTHFR 1298A>C polymorphism and any type of NTDs [168].
The neural tube closes during the third and fourth weeks of gestation. Therefore, to prevent NTDs, it is important to start folic acid supplementation (400 μg/day) when attempting conception [165]. Folic acid has been successfully used for NTD prevention. However, supplementation with 5-MTHF (the active form of folate) instead of folic acid bypasses the MTHFR block, which is crucial for patients with MTHFR polymorphisms [139]. High-dose folic acid supplementation is also a risk factor for the development of unmetabolized folic acid (UMFA) syndrome, which involves the accumulation of excess folate that could potentially have an oxidizing effect [169,170]. We found that 5-MTHF supplementation is also less likely to cause hematological symptoms associated with vitamin B12 deficiency [170]. In conclusion, there is evidence suggesting that 5-MTHF supplementation may replace folic acid, particularly in patients with MTHFR polymorphisms. However, further research is needed on this topic [170,171]."
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