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Causes Of High B12 Without Supplementation

In this article we will discuss the causes of high B-12 without supplementation.  In a previous video we talked about What Does A High B-12 Level Mean and some things to think about with that.  In this article we will explore this topic in a little bit more detail.

The basis of this article is to discuss some of the more serious or problematic things that could be causing your high vitamin B-12. The information in the article is based a research paper that can be found here ( Causes of High B12 Without Supplementation in Clinical Practice ).  If you are having persistently elevated B-12 levels, this information will be helpful.  So keep reading we are going to get into the details.


The causes of high B-12 levels without supplementation are numerous. Before we get into this, we have to take first things first.  Even though the title is "cause of high B-12 without supplementation," my experience helping people figure this out, they are taking B-12.  They sometimes just are not aware of it.  It could be in a multivitamin, a workout drink, a protein powder, or something like this.  So double-check you are not getting B-12 from various sources that you are not aware. 

Now in a previous video we talked about how liver disease and cell membrane issues can be implicated in elevated B-12 levels. This still can be the cause of high B-12 without supplementation but there could be other, more serious, reasons for this as well.  Most of these more serious causes are altering the transportation of B-12 via the transcobalamin transport proteins (more on this below).  Both the cell membrane and transcobalamin proteins can be a part of the issue and solution.  As you will see below look at some of the problems that can come up with the transcobalamin transport proteins and various diseases that can cause elevated B-12 when you're not supplementing with B-12 

Most often, with elevated B-12 levels, it has nothing to do with alterations in these transport proteins called transcobalamin.  This is why most often when you have an elevated B-12 level show up on your lab, it is ignored, pushed to the side.  Essentially if you remain having persistently elevated B-12 levels in the absence of supplementation you should explore this further with more testing. High B-12 levels could be an epiphenomenon or related to a deeper issue with B-12 transportation. 

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Role of Transcobalamin in High B-12 Without Supplementation 

So how is B-12 transported? The chemical name for B-12 is cobalamin and it has to be bound to a carrier protein to move through the blood and more importantly into the cell.  B-12 uses three different carrier proteins to do this TCN 1, TCN 2, and TCN 3.  However only one of these transporters is actually functionally useful in delivering B-12 into its target cells.  It is the TCN 2 transporter that is the main transporter for B-12.  Therefore, anything that raises TCN 1 and TCN 3 will lower the functional activity of B-12 by limiting the binding of B-12 to the TCN 2.  In this case all the B-12 is getting bound up by these other transcobalamins that don't really work well for getting B12 into the cell.  Now this doesn't necessarily explain the elevated B-12 levels but it does explain how one can be deficient in B-12 in the presence of higher serum B-12 levels.  So what is actually causing the high B-12 levels? Let's look at that next. 


Role of Solid Tumors and Hepatitis in High B12 Without Supplementation

In the case that you've ruled out excess consumption of B-12, it makes sense to explore some of these other things.  This does not necessarily mean you have these things but problems that could be going on to cause elevated B-12.  The first thing to consider and rule out is solid tumors as they can cause elevated B-12 levels.  Most commonly it would be liver tumors, hepatocellular carcinoma in particular.  This can lead to elevated B-12 levels due to poor uptake of B-12 in the liver cells.  With liver cancer some of the liver cells are damaged as a result the liver cell are are not expressing as many B-12 receptors.  The same thing happens with liver disease whether it is acute or chronic hepatitis.

Hepatitis and Hepatocellular Carcinoma can also lead to increase release of B-12 from the cells being damaged.  B-12 can be released from the cells because basically it is where most of the B-12 is stored. B12 is stored in the body.  So solid tumors are a cause of high B12 due to increased release of stored B12 and decreased uptake.  There are probably other cases of solid tumors outside of Hepatocellular carcinoma but this was the focus of the research paper.


Role of Blood Cancers in High B12 Without Supplementation

Blood cancers in general can lead to an increase in B-12 levels due to an increased production of these TCN 1 and TCN 3 transcobalamin proteins.  These particular transport proteins are made more commonly in certain cell lines like the granulocytes, a type of white blood cell.  High B12 levels are found in many myloproliferative disease. These are disease of the bone marrow where the white blood cells come from. These disease states result in an increased production of white blood cells including Granulocytes.  As noted Granulocytes have an affinity for producing the TCN 1 and TCN3  and not so much of the TCN 2.  As a result, there is more binding of the B-12 but less of it is getting taken up into the cells because it's all bound by non-functional transport proteins.  Therefore the B-12  just circulates and never gets into the cells.

So how does B-12 get into the cell? Essentially these transcobalamin molecules are carried through the cell membrane after binding to the B-12 receptor on the cell.  So this is still a problem with cell membranes.  However, it can have more to do with the transportation of B-12 rather than the cell membrane. 


Role of Inflammation in High B12 Without Supplementation

Chronic kidney disease can also affect B-12 uptake due to the kidney cells being damaged.  If the kidneys cells have damaged receptors they can no longer take in the B-12 and there is more in in bloodstream.  Many times kidney disease is affected by inflammation and poor antioxidant capacity. 

Separate from kidney disease, inflammation can be another cause for elevated B-12 levels.  Inflammation is very nonspecific but various cases of autoimmune disease, like lupus etc have been described as causing elevated B-12 levels.  With inflammation, there is damage to the cell membranes.  This is how inflammation starts and is perpetuated.  As the cell membranes are damaged there are a cascade of inflammatory molecules produced. When you have inflammation or damage to the cell membranes the transport mechanisms that allow the TCN 1 to take the B-12 through the cell membrane may be altered.


What To Do With High B12 Without Supplementation

So taking all those causes of elevated B-12 level into consideration, the first thing you want to do is find out if you're actually deficient in B-12.  That sounds like an oxymoron,  "you're saying you're high in B-12 but you're actually deficient?  As noted above, sometimes people are actually deficient in B-12.  There are some labs you can do to figure this out. One of them is called methylmalonic acid and the other one is called homocysteine.  Both of which would be elevated in the presence of B-12 deficiency.  with the methylmalonic acid in particular being of importance. 

So if you are finding high B-12 levels and elevated methylmalonic acid, you would want to supplement with B-12 until that methylmalonic acid goes down.  In any case of persistently elevated B-12 levels, you should be explored the other things noted above with preliminary labs to make sure you don't have problems with your white blood cells, kidneys, liver, etc.

These are typical labs that are done in a general screening called CBC and Chem panel.  These may come out normal but if your high B-12 levels are persistent, a thorough investigation with a blood specialist called the hematologist may also be worth while. 

I will be posting another article about what to actually do about high B-12 levels without supplementation and go into a little bit more detail.

hope this video was helpful in giving you a deeper understanding of the causes of elevated B-12 level without supplementation.  Be sure to check out the next article in a few weeks, what to do about elevated B-12 levels.  This one will focus on steps to take, labs to do etc. 


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