How much folate you need per day, and why the unit is the whole problem

1. 01

   The unit is the whole problem: what a DFE is

   Folate is the generic term, food folate is what occurs naturally in food, and folic acid is the synthetic fully oxidised form used in fortification and supplements. They are absorbed at different rates, so requirements are expressed in Dietary Folate Equivalents to put them on one scale (NIH Office of Dietary Supplements). One mcg DFE equals 1 mcg of food folate, or 0.6 mcg of folic acid taken with food, or 0.5 mcg of folic acid on an empty stomach.

2. 02

   The conversion, worked in both directions

   Forward: a 400 mcg folic acid tablet with a meal is 400 divided by 0.6, about 667 mcg DFE; on an empty stomach it is 400 divided by 0.5, exactly 800 mcg DFE. A cereal declaring 400 mcg DFE per serving contains 240 mcg of actual folic acid. Backward: meeting the 400 mcg DFE RDA entirely from food folate takes 400 mcg of food folate, but meeting it entirely from folic acid taken with food takes only 240 mcg (NIH Office of Dietary Supplements).

3. 03

   The RDA by life stage, in DFE

   The RDA is 400 mcg DFE a day for adults, 600 mcg DFE in pregnancy and 500 mcg DFE during lactation, with 150 mcg DFE at 1 to 3 years, 200 at 4 to 8, 300 at 9 to 13 and 400 at 14 to 18 (NIH Office of Dietary Supplements). The Daily Value on Nutrition and Supplement Facts labels is 400 mcg DFE (FDA). The label unit switched to DFE, so an old and a new panel can show different numbers for the same tablet.

4. 04

   The 1,000 mcg upper limit applies to folic acid only

   The tolerable upper intake level is 1,000 mcg a day for adults, and it applies to folic acid from fortified foods and supplements, not to folate found naturally in foods, which has no upper limit (NIH Office of Dietary Supplements). That distinction is not decorative: it means a bowl of spinach cannot contribute to exceeding the UL, while a fortified cereal and a tablet can. It also means the UL and the RDA are quoted in different currencies.

5. 05

   Why a 400 mcg tablet is not 400 mcg toward the RDA

   A 400 mcg folic acid tablet taken on an empty stomach supplies 800 mcg DFE, which is 200 percent of the adult RDA of 400 mcg DFE, while simultaneously being 40 percent of the 1,000 mcg UL for folic acid (NIH Office of Dietary Supplements). Both statements are true because they use different units. That is the most common arithmetic error in folate self-assessment, and it runs both ways: people read their headroom, and their shortfall, wrongly.

6. 06

   The neural tube closes before most pregnancies are recognised

   The neural tube closes during the first month of pregnancy, which is before most pregnancies are recognised, so a recommendation addressed to pregnant women would arrive after the window it protects had closed (NIH Office of Dietary Supplements). That is why women capable of becoming pregnant are advised to get 400 mcg a day of folic acid from fortified foods or supplements in addition to food folate. The recommendation is deliberately addressed to a much larger group than the one it will benefit.

7. 07

   The MRC trial: a 72 percent reduction in recurrence

   A randomised double-blind factorial trial at 33 centres in seven countries enrolled 1,817 women at high risk because of a previous affected pregnancy. Among 1,195 completed pregnancies with known outcome there were 27 neural tube defects, 6 in the folic acid groups against 21 in the groups without, a 72 percent protective effect with a relative risk of 0.28 (95% CI 0.12 to 0.71) (MRC Vitamin Study Research Group 1991).

8. 08

   Fortification since January 1998, and corn masa in 2016

   Since January 1998 the FDA has required enriched breads, cereals, flours, cornmeals, pastas and rice to be fortified with 140 mcg of folic acid per 100 g, and in 2016 permitted the same level in corn masa flour (NIH Office of Dietary Supplements; Williams et al. 2015). The consequence for a reader is that enriched grain products are a folic acid delivery system, so the pantry staples in most kitchens contribute to the folic acid column rather than the food folate column.

9. 09

   What fortification bought: about 1,326 births a year

   Data from 19 population-based birth defects surveillance programs covering 1999 to 2011 put the number of births occurring annually without neural tube defects that would otherwise have been affected at approximately 1,326 (95% CI 1,122 to 1,531), with birth prevalence remaining relatively stable after the initial post-fortification decline (Williams et al. 2015). The same analysis notes remaining prevention opportunities among women with lower folic acid intakes, particularly Hispanic women, which is part of the reason the corn masa provision followed.

10. 10

    The food table, in DFE, and what it mixes together

    Beef liver 3 oz 215 mcg DFE, boiled spinach half a cup 131 mcg DFE, black-eyed peas half a cup 105 mcg DFE, fortified breakfast cereals one serving 100 to 400 mcg DFE, enriched white rice half a cup 90 mcg DFE, asparagus 4 spears 89 mcg DFE, broccoli half a cup 52 mcg DFE (NIH Office of Dietary Supplements; USDA FoodData Central). Cereal and enriched rice are folic acid expressed as DFE, so their true folic acid content is 0.6 times the figure shown.

11. 11

    Folate is water-soluble and heat-labile, so boiling costs

    Folate is a water-soluble vitamin and it is heat-labile, so boiling both leaches it into the water and destroys a substantial fraction, which is why the same spinach can deliver very different amounts depending on preparation (NIH Office of Dietary Supplements). The implication is specific to the vegetable sources: raw salad greens, lightly steamed asparagus and avocado retain more than a long boil does. Fortified grain products are unaffected by this, since the folic acid is added to a dry product.

12. 12

    The B12 masking mechanism is why the upper limit exists

    High folic acid intake can correct the megaloblastic anemia of vitamin B12 deficiency while the neurological damage progresses undetected (NIH Office of Dietary Supplements). Among 1,459 seniors in NHANES 1999 to 2002 with low B12 status, serum folate above 59 nmol/L was associated with anemia (OR 3.1, 95% CI 1.5 to 6.6) and cognitive impairment (OR 2.6, 95% CI 1.1 to 6.1), while in those with normal B12 high folate was associated with protection against cognitive impairment (OR 0.4, 95% CI 0.2 to 0.9) (Morris et al. 2007).

13. 13

    Unmetabolized folic acid and the ceiling on DHFR

    In six human livers from organ donors or surgery, reduction of folic acid by DHFR per gram averaged less than 2 percent of the rat liver rate at physiological pH, with almost a 5-fold variation between human samples (Bailey and Ayling 2009). The authors concluded that benefit from high-dose folic acid will be limited by saturation of DHFR, particularly in people with lower than average activity, and that this is consistent with reports of unmetabolized folic acid in plasma and urine.

14. 14

    Methylfolate and MTHFR, handled skeptically

    Common MTHFR variants, most often C677T, reduce the activity of the enzyme producing 5-methyltetrahydrofolate, and carriers can show higher homocysteine and lower circulating folate. What can be said is that the fortification programme uses folic acid and produced a measured reduction in neural tube defects across a population carrying the usual frequency of these variants (Williams et al. 2015). What cannot be said on current evidence is that carriers should avoid folic acid or that methylfolate improves clinical outcomes.

What people ask us next.

Q01

How much folate do I need per day?

The RDA is 400 mcg DFE a day for adults, 600 mcg DFE in pregnancy and 500 mcg DFE during lactation, with 150 to 400 mcg DFE across childhood (NIH Office of Dietary Supplements). The Daily Value on labels is 400 mcg DFE (FDA). Separately, women capable of becoming pregnant are advised to obtain 400 mcg a day of folic acid from fortified foods or supplements in addition to the food folate in a varied diet.

Q02

What is a DFE and why does it matter?

A Dietary Folate Equivalent puts food folate and folic acid on a single scale, because folic acid is absorbed more efficiently. One mcg DFE equals 1 mcg of food folate, or 0.6 mcg of folic acid taken with food, or 0.5 mcg of folic acid on an empty stomach (NIH Office of Dietary Supplements). It matters because the same number then means different things: a 400 mcg folic acid tablet on an empty stomach is 800 mcg DFE, twice the adult RDA.

Q03

Is folate the same as folic acid?

No. Folate is the generic term for the vitamin in its various forms, food folate is the naturally occurring version in foods such as spinach, lentils and liver, and folic acid is the synthetic fully oxidised form used in supplements and in fortified grain products (NIH Office of Dietary Supplements). The practical differences are absorption, which is why the DFE conversion exists, and regulation, since the upper limit applies only to folic acid from fortified foods and supplements.

Q04

Can you take too much folic acid?

The tolerable upper intake level is 1,000 mcg a day of folic acid from fortified foods and supplements (NIH Office of Dietary Supplements). High folic acid intake can correct the megaloblastic anemia of vitamin B12 deficiency while the neurological damage progresses undetected. Among 1,459 older NHANES participants with low B12 status, serum folate above 59 nmol/L was associated with anemia (OR 3.1, 95% CI 1.5 to 6.6) and cognitive impairment (OR 2.6, 95% CI 1.1 to 6.1) (Morris et al. 2007).

Q05

When should I start taking folic acid before pregnancy?

Before conception rather than after a positive test. The neural tube closes during the first month of pregnancy, before most pregnancies are recognised, which is why the recommendation is addressed to all women capable of becoming pregnant (NIH Office of Dietary Supplements). The trial evidence comes from a randomised factorial study in 1,817 high-risk women, where folic acid produced a 72 percent protective effect with a relative risk of 0.28 (95% CI 0.12 to 0.71) (MRC Vitamin Study Research Group 1991).

Q06

Does cooking destroy folate?

A substantial fraction of it, yes. Folate is water-soluble and heat-labile, so boiling both leaches it into the cooking water and degrades it, which is why the same vegetable can deliver very different amounts depending on preparation (NIH Office of Dietary Supplements). Boiled spinach still supplies 131 mcg DFE per half cup, but raw greens, lightly steamed asparagus at 89 mcg DFE for 4 spears and avocado at 59 mcg DFE per half cup hold their content better.

Q07

Should I take methylfolate instead of folic acid if I have an MTHFR variant?

There is no mainstream recommendation to do so, and the evidence does not currently support treating it as necessary. Common MTHFR variants reduce activity of the enzyme producing 5-methyltetrahydrofolate and can raise homocysteine. But the US fortification programme uses folic acid and produced a measured reduction in neural tube defects across a population carrying the usual frequency of those variants (Williams et al. 2015; NIH Office of Dietary Supplements). Genotype testing to choose a folate form is not part of standard guidance.

Q08

Do I still need a supplement if grain products are fortified?

For a general adult, usually not: 400 mcg DFE is reachable from a varied diet plus the fortified grain supply, and the pantry staples in most kitchens already contribute folic acid (NIH Office of Dietary Supplements). For anyone capable of becoming pregnant, the 400 mcg a day of folic acid is recommended in addition to dietary folate. Check the multivitamin already in use before adding a standalone product, since most contain the full 400 mcg and stacking them is the classic double-count.