The Problem With Blood Tests For Folate

MTHFR mutations change the efficiency with which your body activates folate, so it makes sense to test folate levels, right? Right?

Sadly, folate tests have one big fatal flaw, making them both innaccurate and functionally useless, and the most common folate levels that we see on the blood tests of people with MTHFR might surprise you.

What do Blood Tests for Folate Actually Test?

This test measures the total of all types of folate in the serum, which is the fluid part of blood, excluding red blood cells. This includes the active form of folate, 5-MTHF, but also includes inactive forms like folic acid and unmetabolized folic acid. Because inactive forms of folate are included, this test lacks clinically useful data. UMFA, for instance, indicates an overload of unprocessed synthetic folic acid, which has been shown to impair the conversion to active folate. Having high levels of UMFA is actually a bad sign for folate activity, but high levels of UMFA still show up as “folate” on this blood test.

Why Blood Tests for Folate are Inaccurate and Useless.

Testing for all forms of folate, including those that are useless in their current form (folic acid, natural folates, and every form other than 5-methyltetrahydrofolate), and forms that are actually harmful including UMFA, or unmetabolized folic acid, gives you absolutely no information about functional levels of folate that are being used by your body.

Research generally has shown poor correlation between test results and actual folate-deficient disease states including microcytic anemia, dementia, pregnancy complications having to do with folate deficiency, and neuropsychiatric disorders.

Serum folate is a relatively nonspecific test.(3) Low serum folate levels may be seen in the absence of deficiency, and normal levels may be seen in patients with macrocytic anemia, dementia, neuropsychiatric disorders, and pregnancy disorders.

– Neurology catalog, Mayo Clinic Laboratories.

Normal Range for Folate in Blood Tests

The blood test for folate generally only has a bottom range, with no safe upper limit specified. Typically a normal result is 4 mcg/L or more.

Certainly, if your blood folate tests below 4 mcg, then you have a folate deficiency and should immediately begin supplementing the active form of folate, 5-LMTHF. Sadly, a “normal” looking folate level can’t be trusted.

While an upper range isn’t specified, I often see folate of 12 mcg/L or more in people with the MTHFR mutation, and if the person is undiagnosed, blood folate >12 mcg indicates that the person should be tested for MTHFR gene mutations.

High Folate Levels in Blood Test And Why That Could Mean You Have MTHFR

Having high folate in a blood test looks like a good thing. Hey! I’ve got extra-great folate, except that clinically, people with the MTHFR mutation frequently have high blood folate levels, even as they are having symptoms of low folate. This is likely due to high levels of UMFA and inactive forms of folate in the blood that are unable to be converted to the active form because of the MTHFR deficiency.

In general, if you see blood folate >12 mcg (three times the low-folate indicator) and you haven’t been taking massive doses of folate, then it is important to test for MTHFR mutations.

Other Tests for Folate Status

Other tests for folate status include:

• RBC folate – (not often used, inaccurate, and poorly researched)
• Homocysteine – indicator of folate and/or B12 deficiency, often present in MTHFR gene mutations, MTR gene mutations, and MTRR gene mutations.

RBC Folate Blood Test

RBC folate is a measure of how much folate is in the red blood cells, not the serum which is the fluid around the red blood cells. This test is used far less frequently than the serum folate test. Red blood cells have a roughly 6 – 8 week lifespan and so can indicate folate status over that period of time. In theory red blood cells should contain active folate only, but this tests shows a high coefficient of variation, meaning that performing the test multiple times on the same sample is likely going to yield widely different results. In short, the test isn’t accurate or reliable.

Homocysteine Test To Indicate Folate Levels

Blood tests for homocysteine are most frequently used as a marker for heart disease risk. Homocysteine is an amino acid that is typically low in healthy blood, that is part of something called the methylation cycle. Your body converts the amino acid methionine to homocysteine, and then uses vitamin B12, folate, and vitamin B6 to break down the homocysteine and either recycle it back to methionine, or convert it into other useful substances.

High homocysteine can indicate a deficiency in any of these three B vitamins (B6 (pyridoxine), B9 (folate), or B12 (cobalamin)). It can also indicate a genetic mutation in one of the genes directly involved in breaking down homocysteine including the MTHFR gene, MTR gene, or MTRR gene.

This test is obviously non-specific, and high homocysteine is also being considered as a novel tumor marker in various types of cancer. So while this tests doesn’t directly indicate folate levels, it can show a functional folate deficiency, but is limited because it can also point to a deficiency in other B vitamins.

For more information on homocysteine tests, optimal levels, and homocysteine with MTHFR, read these posts.

MTHFR and Homocysteine: The basics

Methionine, MTHFR, and Homocysteine

MTHFR and Homocysteine By The Numbers

Lowering Homocysteine with MTHFR

Symptoms of Folate Deficiency

The first symptom of folate deficiency is tiredness or fatigue. Symptoms include:

• Fatigue
• Shortness of breath
• Dizziness
• Tender, red tongue
• Mouth sores or mouth ulcers
• Memory loss
• Difficulty concentrating
• Muscle weakness
• Depression
• Diarrhea

Complications of Folate Deficiency

Folate deficiency is a serious issue and has been linked to:

• Infertility
• Certain cancers
• Cardiovascular disease
• Depression
• Dementia
• Alzheimer’s disease
• Decreased Cognitive Function.
• Neural tube defects in babies born to folate deficient mothers.

It is no surprise that these are also all complications associated with the MTHFR mutation.