March 31, 2020
Functional Vitamin B12 Deficiency & Chronic Fatigue Syndrome/ME

Functional Vitamin B12 Deficiency & Chronic Fatigue Syndrome/ME

Scientific research has suggested that the prevalence of micronutrient deficiencies such as Vitamin B12 may be significantly more common than was once expected in the general population.

This may be even more true for individuals with health problems such as chronic fatigue syndrome/ME, auto-immune diseases, neurodegenerative diseases, cardiovascular disease and other illnesses in which oxidative stress plays a key role in the pathogenesis.

I thought functional vitamin b12 deficiency would be an excellent topic to cover on the blog, specifically because it was an issue that I went through myself personally and I have experience of.

Functional vitamin B12 deficiency is a very important issue to highlight to physicians for the simple reason that it often goes undetected and can have absolutely devastating permanent consequences to an individual’s health, especially if discovered too late.

Around my teen years, i developed chronic fatigue, hypothalamic-pituitary-adrenal-axis dysfunction(adrenal fatigue), dysautonomia/POTS and a myriad of other debilitating health problems almost overnight, which would last over a decade and no doctor could ever pinpoint exactly what was causing these issues or exactly why I was so debilitated.

Doctors and physicians are often keen to dismiss that sub-optimal micro-nutrient levels or deficiencies can play a role in either causing or contributing to health conditions, however, we know from solid scientific research that this notion to be incorrect, especially in regards to individuals with chronic fatigue syndrome/ME.

Individuals with CFS/ME, for example, have been shown to be commonly deficient in many nutrients, one example is the “mitochondrial antioxidant” Co-Enzyme Q10, which as research has found deficiency of Co-Q10 is related to the chronic fatigue, autonomic dysfunction, inflammation, oxidative stress, mitochondrial dysfunction and neurocognitive symptoms typically seen in those with CFS.

Another example of a micro-nutrient deficiency, which scientific research has found to correlate to the fatigue seen in individuals with CFS and fibromyalgia is, of course, functional Vitamin B12 deficiency, which we’ll cover more in the article below.

Serum Vitamin B12 Blood Testing Is Notoriously Inaccurate

It was my experimentation with vegan plant-based diets that first led me to have my doctors check my vitamin b12 levels.  Strict vegan plant-based diets do not contain any reliable dietary source of vitamin b12 and thus should not be recommended as healthy diets.

A wealth of robust scientific research has now found that the majority of vegans are deficient in vitamin b12 and suffer from hyperhomocysteinemia, which is a proven factor in the development of cardiovascular disease and plays a role in the etiology of neurodegenerative diseases such as Parkinson’s.

The most common test doctors and general practitioners use to check vitamin B12 levels is blood serum testing, which as we’ll come to in this article is notoriously inaccurate for assessing Vitamin B12 status.

Despite repeated serum vitamin b12 tests over a span of years, my results would always come back normal and acceptable levels, yet the chronic fatigue, autonomic dysfunction, shortness of breath and myriad of other symptoms continued to persist.

It was during my research that I had come across an advanced micro-nutrient test known as spectra cell.  Spectracell tests the white blood portion of a cell for functional deficiencies of vitamins, minerals, antioxidants, amino acids and other nutrients.

I’m very fortunate that the spectracell test had unearthed this “hidden” FUNCTIONAL VITAMIN B12 DEFICIENCY for me.  (See picture below for Spectracell test results).

My Spectracell Test Results Indicating Functional Vitamin B12 Deficiency

Spectracell Functional Vitamin B12 Deficiency

Upon more research, I discovered that there were other case studies reported of individuals having normal Vitamin B12 serum blood levels, but discovering “hidden” functional vitamin b12 deficiency through tests such as elevated homocysteine and MMA(methylmalonic acid).

Functional Vitamin B12 Deficiency Case Study

One study from 2009 described a case of functional vitamin b12 deficiency, where the repeated measurement of a serum B12 level within the normal range led to delay in the diagnosis of subacute combined degeneration of the spinal cord, and possibly permanent neurological damage as a result. [1]

Failure of intracellular transport of B12 by transcobalamin-2 can lead to functional B12 deficiency but with apparently normal serum levels, and is suggested by raised levels of either serum methylmalonic acid or homocysteine, associated with low levels of transcobalamin-2.

Such patients may respond to repeated high-dose injections of Vitamin B12.

Increased Homocysteine, Vitamin B12 Deficiency + Chronic Fatigue Syndrome/ME & Fibromyalgia

A study from 1997 found increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. [2]

The research found that there was a significant positive correlation between cerebrospinal fluid levels of homocysteine and fatiguability.

The study also found that cerebrospinal fluid levels of Vitamin B12 also correlated significantly with the item of fatiguability and with the Comprehensive Psychopathological Rating Scale (CPRS-15).

The correlations between vitamin B12 and clinical variables of the CPRS-scale in this study indicate that low cerebrospinal fluid-B12 values are of clinical importance. Vitamin B12 deficiency causes a deficient remethylation of HCY and is therefore probably contributing to the increased homocysteine levels found in our patient group.

Vitamin B12 Deficiency Symptoms

Vitamin B12 deficiency can cause a whole host of very serious symptoms and if not corrected can even lead to irreparable nervous system damage and cardiovascular disease through elevated homocysteine levels(hyperhomocysteinemia).

Typical symptoms of Vitamin B12 deficiency include extreme tiredness and fatigue, shortness of breath, feeling faint, pernicious anemia, ringing in ears(tinnitus), lack of appetite, sore red tongue, symptoms of dementia, mouth ulcers, walking problems, peripheral neuropathy, vision and mood problems.

Testing For Functional Vitamin B12 Deficiency

As discussed prior in the article, serum vitamin b12 testing should not be relied on solely as a means of checking vitamin b12 status.

Functional markers of vitamin b12 metabolism such as serum homocysteine and MMA(methylmalonic acid) are the standard tests, which are used to diagnose functional vitamin b12 deficiency and assess vitamin b12 status.

Spectracell micronutrient testing such as described above, I believe can be a very helpful test for identifying functional micronutrient deficiencies such as Vitamin B12.

A study from 2003 which investigated the diagnostic value of storage (holoTC) of vitamin B12 and functional markers (methylmalonic acid (MMA)) of vitamin B12 metabolism in populations who are at risk of vitamin B12 deficiency claimed: [3]

Total serum vitamin B12 may not reliably indicate vitamin B12 status.

To get more specificity and sensitivity in diagnosing vitamin B12 deficiency, the concept of measuring holotranscobalamin II (holoTC), a sub-fraction of vitamin B12, has aroused great interest. HoloTC as a biologically active vitamin B12 fraction promotes a specific uptake of its vitamin B12 by all cells

The study concluded:

Our data supports the concept that the measurement of holoTC and MMA provides a better index of cobalamin status than the measurement of total vitamin B12. HoloTC is the most sensitive marker, followed by MMA.

The use of holoTC and MMA enables us to differentiate between storage depletion and functional vitamin B12 deficiency.

Renal patients have a higher requirement of circulating holoTC. In renal dysfunction, holoTC cannot be used as a marker of vitamin B12 status.


1. Functional vitamin B12 deficiency

2. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome.

3. Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk.

The information in this article has not been evaluated by the FDA and should not be used to diagnose, cure or treat any disease, implied or otherwise.

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