Vitamin B12 and Folate : When Should you Take them Together?

Vitamin B12 and Folate : When Should you Take them Together?

Vitamin B12 (also known as cobalamin) and folate (also known as vitamin B9, and sometimes referred to by the name of its synthetic form, "folic acid") are two critical vitamins that are members of the B complex. The B complex is a set of 8 vitamins that need to be consumed each day.

B12 and folate both have important roles in brain functioning and energy production and they are interrelated. It's easy to confuse a B12 deficiency with a folate deficiency.

This article will explain the role of B12 and folate in the body, vitamin B12 deficiency symptoms, folate deficiency symptoms, and the folic acid and vitamin B12 relationship in the body. We'll explain when you should supplement with just one, and when you should take both vitamin B12 and folate.

Vitamin B12

Vitamin B12, also known as cobalamin, is typically found in animal products and is required for DNA synthesis, nervous system functioning because of its role in the production of myelin, and the production of red blood cells.

It's considered the most complex nutrient and one that must be consumed either from supplements or certain animal products like red meat. In addition to that, absorption become more difficult as we get older due to reduced production of a protein called "intrinsic factor", so deficiency is common. 

Vitamin B12 deficiency symptoms

The initial vitamin B12 deficiency symptoms can be hard to spot. You may feel tired, weak, have poor concentration or ability to focus.
As the deficiency advances, you may experience problems with mobility, tongue swelling, nausea, or even memory blackouts.
Here's a list of some common B12 deficiency symptoms:
  • Muscle weakness
  • Fatigue/tiring easily
  • Changes to mood/irritability
  • Numbness, tingling in hands and feet
  • Smooth or swollen tongue
  • Nausea
  • Diarrhea
  • Changes to heart rate
  • Fast heart rate
  • Sudden weight loss

If you're experiencing any of these symptoms, you should get a blood test to confirm deficiency.


Folate, or vitamin B9, performs many similar functions to B12. It's critical for red blood cell synthesis, and also helps break down an amino acid called homocysteine that's harmful in large amounts.

You can find folate in dark leafy green vegetables, peas, nuts, and beans. It's also in many fortified foods in its synthetic form, folic acid (note that folic acid is destroyed during cooking).

Folate is especially important during pregnancy for its role in preventing neural tube defects for a developing fetus.

Folate deficiency

Folate deficiency can be difficult to distinguish from B12 deficiency because the symptoms will look the same (see "vitamin B12 deficiency symptoms" section above).
A folate deficiency and B12 deficiency can occur together, and typically both will (and should) be tested for if a patient exhibits the symptoms of B12 and/or folate deficiency. The typical process for diagnosing either is explained in the next section.

How are B12 and folate deficiencies distinguished?

B12 and folate deficiencies can only be distinguished by testing your blood. This section gets technical!

Low B12 and folate both cause something called "macrocytic anemia", and this will be diagnosed using a complete blood count (CBC) and peripheral smear (PS). 

When these tests are performed, both would result in low hemoglobin and hematocrit levels. Something called the "mean corpuscular volume" (MCV) would be above 100, and the PS would show macrocytic (in laymen's terms, enlarged) red blood cells and what's called "hypersegmented neutrophils" (extra segments on a type of white blood cells).

The two will be distinguished from one another mainly by looking at the serum folate and B12 levels.

Folate serum levels below 2 ng/mL indicate deficiency, while >4 ng/mL is considered normal. Levels between 2 and 4 will need to be investigated by measuring methylmalonic acid (MMA) and homocysteine levels (yes, we understand your eyes might be crossing by this point).

A blood serum B12 level below 200 pg/mL is considered deficient. Above 300 pg/mL is considered normal, and between 200 pg/mL and 300 pg/mL is "borderline" and enzymatic testing will need to be done to check further for deficiency.

If you have a normal blood B12 and MMA level and elevated homocysteine, you have only a folate deficiency.

If you have high MMA and homocysteine and low B12, you have only a B12 deficiency. (1)

You may be low in both B12 and folate. A blood test including serum folate and B12 levels as well as MMA and homocysteine can confirm this.

Folic Acid and Vitamin B12 Relationship

Folate and B12 have intersecting functions in something called the methylation cycle, an extremely important process in the body. One example of a critical methylation process is the production of myelin basic protein. When this is disrupted (for example, because of B12 deficiency), it can result in degeneration of the spinal cord.

When the body is low in folate and/or B12, you develop a form of anemia called pernicious anemia which results in your body producing abnormally large red blood cells which can't be used properly by the body. About 34% of anemia in the US is caused by low B12 and/or folate.

Consuming too much folate but not enough B12

It's been hypothesized that consuming too much folic acid (due to the fact that many foods are fortified) and not enough B12 can "mask" the signs of a B12 deficiency. This is because of something called the "methyl trap hypothesis".

This hypothesis is that in the absence of adequate B12, the folic acid will become "trapped" as 5-methylTHF, a form of folate that's not suitable for DNA synethesis. In other words, even though the body has enough folic acid, the cells will suffer a form of folate deficiency.

The consequence of this will be a form of anemia that looks identical to actual folate-deficiency anemia.

When someone with this trapped folate begins treatment with B12, the myelination will restart and trapped folate will be released, allowing the DNA synthesis to resume and the deficiency to slowly but surely be reversed.

Taking high concentrations of folic acid (the synthetic form) will initially appear to treat the anemia, as it will allow for DNA synthesis to resume. However, this will not restart the methylation cycle because it is dependent on a B12-dependent enzyme called methionine synthase. 

So the nerve damage and associated symptoms will continue and the nerve damage may become irreversible if not quickly treated with B12 supplementation or intramuscular injection. (2)

Even a slight B12 deficiency in the presence of excess folic acid will cause high homocysteine levels.

Take B12 and Folate Together

There is currently no human research to confirm whether giving high doses of folic acid to those with low B12 will accelerate neurological degeneration. This is because performing such a study would be unethical.

However, a large study did confirm that for those with low B12, as folate status increased, so did the level of the harmful metabolytes homocysteine and methylmalonic acid. (3)

Keeping the hypothesis discussed in the previous section in mind, we can conclude that it's a good idea to take vitamin B12 with any folate supplement and avoid high doses of folic acid when one shows signs of pernicious anemia, or any of the shared symptoms of folate and B12 deficiencies.

You should confirm via a blood test which deficiency you actually have and which supplement is appropriate for you.

Because of the widespread fortification of folic acid, some people may experience masked low B12 symptoms in the early stages of a deficiency and it's for this reason many people are not in favor of widespread fortification of food with synthetic folic acid, despite the fact that this can be helpful for pregnant women to prevent spinal cord defects.

What about B12 fortification?

The obvious answer to the problems associated with folic acid fortification would be to fortify food with B12 as well, right?

The problem with this (besides some arguments from food producers, like B12 changing the color of flour) is that the main cause of B12 deficiency isn't the absence in food - it's an absorption issue.

That's why it's important to take high doses of B12 to treat a deficiency. You may notice that all the Why Not Natural supplements contain a high concentration of B12. This is intentional: you only absorb about 1% of what you take in supplements through a process called passive diffusion. (3)

You can find Why Not Natural's B12-folate supplement, in an unflavored, bioavailable liquid form with a high dose of B12, here. The Why Not Natural liquid B12 is here.

All You Need to know about Vitamin B12 and Folate


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