B12: Not “Just a Simple Vitamin”

by Greg McClure

I became aware of my vitamin B12 deficiency problems the same way most people do — after it started damaging me. 

I was in my late fifties and I began having problems concentrating, plus I was experiencing numbness and tingling in my toes and fingers.  Once I became aware of these problems, I also noticed that they were getting progressively worse. 

At first I suspected hypothyroidism since it runs in my family and I had other symptoms, but I secretly feared that it was Alzheimer’s or diabetes. I went through two primary care doctors and a naturopathic doctor and continued to decline without a firm diagnosis or successful treatment of any kind.

For many people with the same experience, the end result is to eventually be misdiagnosed and unsuccessfully treated for one disease after another.  I was more fortunate than many in that I found a medical professional (a nurse practitioner) who correctly identified part of my problem to be vitamin B12 Deficiency. 

She was the first to even test me for B12, and my result (254 pg/ml) would still have not warranted treatment from many physicians.  However, she asked if I would be willing to try an injection of B12.  I did, and when I woke up the very next morning I could tell a difference.  Not like turning on a light switch — it would take several months before these problems completely cleared up — but I just felt better.  I knew this was the solution.

Enthused and eager to learn more, I started my ongoing research into vitamin B12.  Through the websites and works of Eric Norman, Ph.D. (Norman Clinical Laboratory, Inc.) and Sally Pacholok, R.N. and Jeffrey Stuart, D.O. (Could it Be B12?) I soon discovered the possible contributor to my B12 problems. 

Just before I started experiencing the cognitive issues, I had two dental procedures over the course of three months.  I requested and received nitrous oxide as a sedative.  What I didn’t know then is that nitrous oxide inactivates the active B12 in the bloodstream. [1]

Why did it take so long for someone to figure out my problem?  My case is a perfect example of why B12 is different from other vitamins and how it is often missed.  Here’s a simple overview of why vitamin B12 deficiency is so important, and how it gets overlooked.

First, the systems and processes that vitamin B12 impacts are widespread and can cause serious harm: [1] [2]

  • Neurological
  • Neuropsychiatric and Psychological
  • Cardiovascular System
  • Genitourinary (reproductive) System
  • Hematologic (Blood) System
  • Immunologic System
  • Integumentary System (Skin, Hair, Nails, etc.)
  • Musculoskeletal System
  • Respiratory System
  • Methylation of DNA

Second, unlike most other nutrients, vitamin B12 must go through a complex absorption and utilization process that is subject to innumerable problems due to a variety of issues including:  [1] [2]

  • Decreased nutritional intake in diet (i.e. vegans, vegetarians, macrobiotic diets)
  • Malabsorption problems:
    • Autoimmune Diseases (I.e. Pernicious Anemia, Crohn’s Disease)
    • Digestive Problems (i.e. gastritis, gastric bypass surgery, etc.)
  • Pharmaceutical Medications (i.e. metformin for diabetes, and PPI Inhibitors and H2 Blockers for heartburn, etc.)
  • Bacterial (i.e. h. pylori which causes stomach ulcers and blind loop syndrome, an overgrowth of bacteria in the small intestine)
  • Genetic problems with metabolism (i.e. MTHFR gene mutation)

Now that we know vitamin B12 Deficiency can cause serious harm and is subject to innumerable complex absorption and utilization issues, let’s compound these problems with an ongoing conflict about testing.  While the current standard of care is the serum B12 test, it has several drawbacks:

The serum B12 test measures total B12, but only about 20% of the B12 in serum is in the biologically active form the body can use known as transcobalamin II. [1] 

This probably contributes to the test not being very accurate with a sensitivity (true positive) rate of about 60% and a specificity (true negative) rate of about 40%.[3]  That, in turn, has created conflict over the correct reference range to use. 

The standard of care identifies vitamin B12 Deficiency as “below 200 pg/ml”.  However, there is much evidence to support that damage can occur in patients with levels as high as 550 pg/ml, which is about mid-range for many labs (~200 - 1,100 pg/ml)! [1]

There are two other tests commonly used to diagnose vitamin B12 deficiency, but they also have issues:

Serum homocysteine’s results can be affected by vitamin B6 deficiency, folate deficiency, and other disorders. [1] Because of that, the test’s sensitivity and specificity are both only about 50% [3]

Serum methylmalonic acid’s results can be affected by kidney disease, thyroid disease, pregnancy or other factors.  [1]   In spite of that, the test’s sensitivity is a little better at about 80%, but still lags on specificity at about 60%. [3]

To further compound the confusion over testing, the test that appears to me to be the most accurate test to diagnose vitamin B12 deficiency at the cellular level, the urinary methylmalonic acid test (uMMA), is seldom ordered, and just as seldom included in studies.  With a sensitivity of 100% and specificity of 99%, the test is non-invasive and is the most accurate test for seniors. [3]

Greg McClure

B12: Not “Just a Simple Vitamin” part 2


[1]   Sally M. Pacholok, R. N., B.S. N. & Dr. Jeffrey J. Stuart, D.O. (Could It Be B12?; Could It Be B12?, 2nd Edition, What’s Wrong with My Child?)

[2]   Eric J. Norman, PhD. (Norman Clinical Laboratory, Inc.), website: www.B12.com).

[3]   Eric J. Norman, PhD. (Norman Clinical Laboratory, Inc.), from a 2009 literature review, appearing on informational flyer. 

February 2016