Building Babies Brains – Folate

Eat For Baby - Blog - Articles - Folate

Over the next few blogs we will dive a little deeper into brain boosting nutrients. Let’s start with folate.

Folate

The majority of women on their pregnancy journey will have heard of folate. Folate is an essential nutrient for pregnancy to ensure that the fetal spinal cord, and our babies’ brains, develop properly. We decided to start this blog series with folate because we figured it would be pretty straightforward:

  • make sure you take your folate supplements during pregnancy to prevent neural tube defects
  • a bit of background on how the association was discovered
  • what the mechanism of action is
  • provide the current recommendations
  • encourage eating folate rich food over supplements, acknowledging the challenge of getting folate from foods (it must be difficult or we wouldn’t all be encouraged to supplement right?) – blog finished...

But what we discovered was far from straightforward. Did you know that folate and folic acid, are not the same thing? That in fact:

  • our bodies respond differently to folate and folic acid
  • current guidelines recommend folic acid supplementation and only until the end of the 1st trimester
  • it’s incredibly easy to derive your folate needs from food, even during pregnancy when our requirement increases
  • there are upper limits to the amount of folic acid that is safe for our body, and some women during pregnancy exceed these safe upper limits.

This just got way more interesting and need-to-know. Let’s dive in.

A brief history of folic acid supplementation in pregnancy

The link between folate deficiency and neural tube defects was discovered in the 1960s when women delivering babies with serious birth defects, notably neural tube defects, were more likely to have impaired folate status, than women with unaffected children. In the late 1970s and early 1980s, a clinical trial (not randomised) of a multivitamin, including folic acid, in women who had a previous pregnancy with a neural tube defect, showed that the risk of recurrence of neural tube defect was greatly reduced. A randomised controlled trial followed (again using a multivitamin that included folic acid) and it was concluded that folic acid daily was effective at protecting against neural tube defects. Since then, some of our food supply (like flour) has undergone fortification with folic acid.

Folate and folic acid are not the same thing

Folate is the naturally occurring form of vitamin B9. Folate is derived from the Latin ‘folium’, meaning leaf – and yes, green leafy vegetables are some of the foods highest in folate. In our digestive system, the majority of folate is converted to the biologically active (i.e. can be used by our cells) form of folate, levomefolic acid or 5-methyltetrahydrofolate (5-MTHF). 5-MTHF enters the bloodstream to be taken up by cells as required.

Folic acid is the synthetic form (made in a laboratory to be a similar chemical structure to folate, but not identical) of vitamin B9, also known as pteroylmonoglutamic acid. Folic acid needs to be converted into the bioactive form of folate in the liver to be used by our bodies. There is evidence that this conversion process is slow and it can mean that folic acid levels stay high for a long time after taking a supplement. Evidence also suggests that folic acid can mask a vitamin B12 deficiency.

Why do we need folate?

Folate plays an important role in the division of new cells and facilitates the production of DNA and RNA, our bodies’ genetic material. Fundamentally, a baby’s growth and development occurs because cells are dividing. Take baby’s brain for example, from as early as 4 weeks in gestation, hundreds of thousands of new neurons are forming every minute!

Folate works closely with vitamin B12 to make red blood cells and helps iron function properly in the body. Folate is involved in many cellular processes in our bodies, including methylation. Methylation is the process of moving a methyl group (1 carbon and 3 hydrogen atoms), onto and off proteins, amino acids, enzymes and DNA and is critical for our survival. Methylation is involved in turning our genes on and off, processing chemicals and toxins, building neurotransmitters (chemicals in our body that communicate information between our nerves), processing and metabolising hormones (chemicals in our body that communicate information between different organs), building immune cells, synthesising DNA and RNA, producing energy, and protecting our nerves by producing the outer sheath, myelin. Folate, as well as vitamin B12, choline and methionine are critical for methylation. Deficiencies in any of these nutrients can wreak havoc in the methylation pathways, disrupting the associated functions.

Since the fortification of foods with folic acid, and the widespread public health messaging encouraging women to take folic acid supplements, Australia has seen ~14% reduction in the rate of neural tube defects. There are still ~40 babies with neural tube defects / 100,000 births. More recent evidence suggests that it is unlikely to be folate status alone that is responsible for neural tube defects, but instead the involvement of whole methylation metabolism. Of course, the research continues.

Eat Folate Rich Food

Despite the abundance of folate rich foods (see table below), few Australians eat enough of these daily to derive adequate folate intake. Hence the fortification of our food supply and the booming supplement industry. But it’s not that difficult to meet your daily folate needs with food.

Foods Naturally Containing Folate

mcg folate /100g food*

Approximate Household Measure*

Seaweed, nori, dried

1400

35mcg/nori sheet

Cabbage, Chinese flowering, raw

425

1.5 cups

Lime, native, fruit

347

whole fruit

Watercress, raw

280

2 cups

Cabbage, mustard, raw

278

1 cup

Cabbage, Chinese flowering, boiled, drained

266

1 cup

Cabbage, mustard, boiled, drained

246

1 cup

Nut, peanut, with skin, raw, unsalted

240

2 handfuls

Seed, sunflower

229

3/4 of a cup

Spinach, water, fresh, raw

225

1 cup

Quandong, fruit, flesh

191

1/2 cup

Egg, chicken, yolk, hard-boiled

180

6 egg yolks

Cabbage, Chinese, raw

170

1 cup

Rocket, fresh, raw

164

1 cup

Seaweed, boiled, drained

164

1/2 cup

Spinach, baby, fresh, raw

162

1 cup

Broccoli, fresh, raw

158

1 cup

Broccoli, fresh, baked, no added fat

154

1 cup

Endive, fresh, raw

142

1 cup

Kale, raw

141

1 cup

Bean, haricot, dried, boiled, drained

14

1/2 cup

Muesli, toasted/untoasted, added dried fruit & nuts

130

1 cup

Bean, red kidney, dried, boiled, drained

130

1/2 cup

Beef, corned, canned

127

2-3 slices

Broccolini, fresh, raw

123

1 cup

Pasta, gluten free, boiled from dry, no added salt

120

1 cup

Nut, hazelnut, raw, unsalted

113

2 handfuls

Egg, chicken, whole, raw

110

2 eggs

Chicory, raw

110

1 cup

Spinach, Mature English, fresh, raw

110

1 cup

Beetroot, fresh, purple, peeled, baked, no added fat

107

1 whole

Cabbage, Chinese, boiled, drained

106

1 cup

Asparagus, green, raw

99

~4 stems

* 1 cup measure for greens / cabbage means pushed down and packed in

* Folate content in foods derived from Food Standards Australia New Zealand (2019). Australian Food Composition Database – Release 1. Canberra: FSANZ. Available at www.foodstandards.gov.au


During pregnancy, to achieve your 600mcg dietary folate requirement, you could eat:
1.5 cups raw chinese flowering cabbage (think coleslaw)  425mcg
2 handfuls of peanuts  240mcg
OR
1 cup raw spinach / rocket / watercress (think side salad)  160-280mcg
1 cup cooked broccoli  154mcg
1 handful hazelnuts  113mcg
1 baked beetroot  107mcg
½ avocado  90mcg
OR
½ cup of haricot or kidney beans  130mcg
1 cup muesli with dried fruit  130mcg
½ cup quandong  180mcg
Corned beef  127mg

Of course, you aren’t just getting folate from this bounty of goodness, you are getting iron, potassium, manganese, vitamins A, C, K, E, calcium, fibre, and the list goes on. Fewer than 95% of Australians eat the recommended number of vegetables each day (6 serves/day). This means the overwhelming majority of Australian’s are missing out on the nutrient bounty that our vegetables deliver. You can start to see why we might have so many issues with poor health and vitamin and mineral deficiencies…

Supplementation

The guidelines are consistent and clear on one thing, women's folate levels should be adequate before conception and throughout pregnancy. This is because cellular division is an essential part of our babies’ development from the very moment of conception. Australian women are recommended to take 500 micrograms of folic acid supplement per day from 12 weeks before conception through to the end of the first trimester.

There are supplements that contain folate or its bioactive form 5-MTHF. These have been less studied in pregnant populations than folic acid, but the evidence so far suggests that supplemental 5-MHTF can effectively improve folate biomarkers in young women in early pregnancy.

The recommendations do not make any claims about taking folic acid after the 1st trimester, but given most women take an off the shelf prenatal vitamin that is static throughout pregnancy, the majority of women who take a folic acid supplement, do so for the duration of pregnancy. The guidelines do not consider whether a woman is eating adequate folate rich foods, the amount of folic acid women are exposed to via fortified food, or the concentration of folate in a woman’s blood before making these recommendations.

Are there risks associated with folic acid supplementation?

Yes. There is evidence from large population studies, that women who take folic acid supplements during pregnancy can exceed the recommended tolerable upper limit of folic acid (1,000 mcg/day). Women who take the recommended folic acid supplement, plus consume adequate folate rich foods have also been reported to reach supra-nutritional folate status. High supplemental intakes of folic acid have been shown to be related to adverse neurological effects in people with vitamin B12 deficiency as they can precipitate or exacerbate the B12 deficiency. High folic acid intake is also associated with general toxicity, risk of cancer and adverse reproductive and developmental effects.

Parts of the world's food system have been fortified with folic acid. In Australia, this is limited to wheat flour (2-3mg of folic acid are added to each 1 kg of wheat flour) to be used for bread making (organic flour is excluded). In the USA breakfast cereals, as well as flours have been fortified with folic acid. This can make it easier for people to exceed the recommended intake of folic acid.

Whether high folic acid throughout pregnancy can have negative effects for our babies’ is still a matter of debate. Some studies suggest that high folic acid late in gestation is associated with asthma and allergic diseases in children, and others do not. Other studies show an increased risk of autism with high folic acid late in gestation and others do not. Women who took 1,000mcg / day or more of folic acid during the periconception period were more likely to have children with lower scores on several tests of cognitive development at ages 4-5 years than mothers who took 400 mcg to 999 mcg folic acid.

Importantly, these studies are all looking at high folic acid supplementation, not high dietary folate intake. In fact all of the ‘risks’ are associated with folic acid supplementation. There is no safe upper limit set for folate rich foods, you can eat as much of these as you desire.

So does anyone really know?

We can feel frustrated and confused by the contradictory science and messaging, or we can accept the complexities of vitamin metabolism (natural and synthetic) in our bodies, particularly during pregnancy. Science is still only scraping the surface of how our body metabolises many vitamins, what role the placenta plays in this process during pregnancy and even the role of our microbiome in metabolising and synthesising vitamins. For example, there are several strains of bacteria that are able to contribute to the synthesis of folate in our gut, and at least one that can complete the synthesis of folate.

When we feel unsure, we can always come back to the ancient wisdom that has seen humans survive for many years! Getting our vitamins and minerals from food sources, and the bacteria that colonise our gut is always going to be easier on our body and give our bodies a more complete nutrient profile than singling out individual vitamins and minerals with supplements.

Eat For Baby Suggestions

Folate is one of many abundant and beneficial vitamins that we can derive from a diet high in plant materials. It will help us to thrive during pregnancy and in everyday life. The guidelines remain for Australian women to take a 500 mcg folic acid supplement per day from 12 weeks before conception through to the end of the first trimester (higher for women who are at high risk under medical supervision).

We suggest seeking advice from your care providers on whether you need to take supplements. Discuss your diet including the amount of bread products you eat (as these contain added folic acid) and the amount of folate rich foods you eat daily, and ask to have blood work done to measure your folate concentrations. If you do require supplementation, have your care provider help you sort through the options and choose the one with high quality ingredients that guarantees their purity and quality and have a conversation about supplements with folate or 5-MHTF rather than folic acid. If you decide to take a prenatal supplement with folic acid, find one that reduces the folic acid concentration after the first trimester to align with the recommendations.

It is our position that food will always be the best option for getting our vitamins and minerals. We have shown you how easy it is to obtain your daily folate requirements from food. Eat lots of vegetables, particularly cabbage, spinach, kale, beetroot and broccoli, nuts and seeds, all grown organically where possible, because pesticides are a toxin that we need to avoid during our pregnancy journey. Support your gut microbiome with a regular intake of probiotics  think yoghurt, kefir, kim chi, and other naturally fermented foods to support vitamin formation by these bacteria.

What we eat matters for our health, and our future babies health. Learning how to harness the benefits of healthy eating can leave us feeling like we’ve stumbled across something a little bit magical.


References

Barua S, Kuizon S, Junaid MA 2014, Folic acid supplementation in pregnancy and implications in health and disease. J Biomed Sci 21:77.
Hilder L, 2016, Report: Neural Tube Defects in Australia, 2007–2011: Before and after implementation of the mandatory folic acid fortification standard. National Perinatal Epidemiology and Statistics Unit, University of New South Wales.
Kim YI 2007, Folate and colorectal cancer: an evidence-based critical review Mol Nutr Food Res. 51:267–92.
Kok DE, Steegenga WT, Smid EJ, Zoetendal EG, Ulrich CM, Kampman E, Bacterial folate biosynthesis and colorectal cancer risk: more than just a gut feeling. Crit Rev Food Sci Nutr. 2018 Dec 3:1-13.
Moussa HN, Nasab SH, Haider ZA, Blackwell SC, Sibai BM, 2016, Folic acid supplementation: what is new? Fetal, obstetric, long-term benefits and risks, Future Sci OA 2(2): FSO116.
Obeid R, Holzgreve W and PietrzikJ K. 2013 Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects? Perinat. Med. 41(5): 469–483.
Valera-Gran D, Navarrete-Munoz EM, Garcia de la Hera M, Fernandez-Somoano A, Tardon A, Ibarluzea J, et al. Effect of maternal high dosages of folic acid supplements on neurocognitive development in children at 4-5 y of age: the prospective birth cohort Infancia y Medio Ambiente (INMA) study. Am J Clin Nutr 2017;106:878-87.
Ward, NJ, 2011, Commentary: A brief history of folic acid in the prevention of neural tube defects, Int J Epidemiology 40:1154-1165.
Wiens D, DeSoto CM, 2017, Is high folic acid intake a risk factor for autism? – A review. Brain Sci 7(11):149.

Australian and New Zealand Nutrient Reference Values for folate –https://www.nrv.gov.au/nutrients/folate
Folate content in foods derived from Food Standards Australia New Zealand (2019). Australian Food Composition Database – Release 1. Canberra: FSANZ. Available at www.foodstandards.gov.au
RANZCOG Vitamin and  Mineral Supplementation Guidelines for Pregnancy –
https://www.ranzcog.edu.au/RANZCOG_SITE/media/RANZCOG-MEDIA/Women%27s%20Health/Statement%20and%20guidelines/Clinical-Obstetrics/Vitamin-and-mineral-supplementation-in-pregnancy-(C-Obs-25)-Review-Nov-2014,-Amended-May-2015_1.pdf?ext=.pdf (currently under review).


 

Written by

Dr Hayley Dickinson, PhD


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