Don’t Let The B12 and Folate Blood Test Mislead You!

An unfortunate mistake I observe repeatedly in my naturopathic practice is B12 and folate blood tests misinterpreted. Blood testing is a common format for many evaluations, but it’s not the entire place where B12 and folate are observed. Because of the different forms of these vitamins, various tissue-level needs, and genetic considerations, you need to understand the entire story before you mistakenly stop supplementing.

If the serum (blood test) levels of B12 and folic acid come back elevated, many times advice is given to discontinue these vitamins. This is done without ever evaluating the tissue biomarkers, assessing for methylation abilities, or even asking when you took the last dose of these vitamins. Understanding how B12 and folate are truly evaluated will help you accurately know your body’s needs.

When was your last dose of B vitamin prior to testing?

This is the first question I ask when these tests come back elevated. Supplemental B vitamins, while water soluble, spike days after the last dose. Generally, we advise to be off B vitamins 5-7 days after the last dose. It does depend upon how much you are taking, so if the dose is 1-2 mg or less, discontinuing 3-4 days will work. Injection or IV Bs are a different story, so err on the side of 5-7 days. Be off Vitamin B’s before you have them tested so you have an accurate reading of your body’s baselines.

What forms of B12 and folate are measured on the blood test?

The answer: None. The blood test does not assess the forms of these vitamins. Cobalamin is the official name of B12 and the various forms in the body are hydroxocobalamin, adenosylcobalamin, methylcobalamin. Tetrahydrofolate, 5-methyltetrahydrofolate, and folinic acid are three important forms of folate. Each type exists in different tissues in different ways to do different things - from running detox pathways, reducing inflammation in your blood vessels, and regulating enzymes for stabilizing neurotransmitters and hormones, not to mention cell repair.

When you read the blood result of B12 and folate, you are not reading the methylated form. It’s a general mixture of all forms. You could really be low in methylcobalamin and methylfolate, yet have the blood tests come back normal or even elevated.

Especially if the methyl forms are being used for neurotransmitter and hormone balance, stopping these can have a major impact on mental health. In addition, some people require high doses of hydroxocobalamin to stabilize cardiovascular inflammation. Stopping this supplement can increase risk factors for a heart attack or stroke. If the serum values are low, then yes, you can assume tissue levels are low. But an elevated level requires a look at the tissue biomarkers.

What are the tissue biomarkers?

Homocysteine, Methylmalonic Acid (MMA), Mean Corpuscular Volume (MCV) are three main biomarkers for B12 and folate. Homocysteine is an amino acid and B12, B6, and folate are used to break it down. An elevated homocysteine is a sign that these vitamins are depleted. If homocysteine stays high, it can build up in your arteries and cause damage leading to blood clots. An increased homocysteine increases your risk for heart attack, stroke, vasculitis, and aneurysm.

Methylmalonic acid is the breakdown product of protein and fat cellular turnover and can be measured in blood or urine. B12 is required for this process, without it, MMA will build up in your body. MMA is the confirmation test for B12 deficiency NOT the serum level.

On the CBC (Complete Blood Count) panel, the MCV is listed. Your red blood cells are matured in the bone marrow with the presence of B12 and folate. Baby red blood cells are large, adult RBCs are small (specifically 79-89 fL). Especially when the size is 92fL or above, we suspect the tissue levels of these vitamins to be low. Large elevations (greater than 97fL) in MCV, indicates macrocytic anemia, which is the type of anemia from lack of B12 and folic acid.

Do you genetically not methylate?

Vitamin B12 and folic acid require an activation process called methylation in order for your body to make use of them. Methylation is a process your body undertakes trillions of times every second - imagine billions of on/off switches inside your body that control everything from energy production and brain chemistry to your stress response and the repair of cells. We are seeing that a significant portion of the population (up to 40%) do not naturally produce sufficient enzymes required for this process. This can spell problems for the body, such as a depleted immune system, fatigue, or increased anxiety and depression.

Methylation activates these vitamins, allowing them into tissues to do business. Think of it like this – the B12 and folate blood levels are like a river and a methylation problem is like a boulder blocking that flow. The unmethylated B12 and folate will pool in the blood. Simply not taking B vitamins would be trying to unblock the dam by taking out the entire river. Instead, giving appropriate methylation support will “remove the boulder” by stabilizing the blood levels and supporting tissue levels.

Genetic testing exists to determine methylation status in the body. The folic acid serum test is a useless and inaccurate marker for understanding methylfolate levels. Especially if you know genetically that you do not methylate, do NOT use folic acid serum levels to determine an accurate status. Homocysteine and genetic testing are the two places we evaluate methylfolate.

What is the serum test actually used for?

Looking at the levels of Vitamin B12 (cobalamin) and folic acid in your blood can help diagnose different types of anemias, investigate neuropathy, and evaluate general nutritional status. Low levels reflect the aspects of these conditions, while high levels may be significant for blood disorders (polycythemia vera or leukemia) or liver disease (cirrhosis or hepatitis). The serum level may be the starting place for further evaluation, not the determinant for managing these vitamins.  

To Recap

The blood test for B12 and folate can be misleading. If elevated, it does not automatically mean you should stop taking all B vitamins. This actually indicates that methylcobalamin or methylfolate is necessary, and likely deficient. Homocysteine, MMA, and MCV are tissue biomarkers to truly assess this nutrient status. Genetic testing is key in understanding the form needs for these vitamins.

If this all seems confusing, don’t worry, you’re not alone! As we have learned more about the forms of the vitamins, the usage of this test changed. I still see healthcare providers giving old advice with regard to blood levels. That can be very frustrating for you upon hearing inconsistent advice.

Remember, as we learn more about the methylation process of B12 and folate, we find the typical serum B12 and folic acid labs may reflect different information. In order to get a clearer picture, it is important to evaluate homocysteine, MMA and MCV tests. If you have been told to stop taking your B12 or folic acid due to elevated blood levels, ask your doctor to evaluate your methylation status and confirm with the tissue biomarkers. The news may surprise you!