The case of persistent low B12 levels

By Corie Edwards

The benefits to having B12 vitamin within normal levels in the body are vast, but treating low B12 levels is not as straightforward as some might think.

Patients with low B12 levels frequently present with fatigue, difficulty losing weight, neurological symptoms such as numbness, megaloblastic anemia, and neurotransmitter imbalances.   Most often, oral or sublingual supplementation is sufficient to raise their serum levels of this important nutrient. 

Recently, I was working with a patient for whom this was not the case, and in the process I uncovered some interesting things about the genetics of B12 deficiencies. 

For some time, I had been working with a female patient who first came to me when she was 28 years old.  She had originally presented to the clinic with complaints of difficulty losing weight and fatigue, though she was otherwise healthy.

I took a thorough history and find nothing remarkable in her past medical history or family history.   She was 5’4’’ and 168 pounds with a BMI of 28.8. All other physical exam findings were within normal range, including blood pressure. 

I ordered routine blood work, including Complete Blood Count, Comprehensive Metabolic Panel, anda Thyroid Panel.  Results showed that the patient suffered from megaloblastic anemia, as well as low serum B12 levels.  The patient was resistant to vitamin B12 injections, so an oral supplement was prescribed at therapeutic levels, 500 mcg once a day. 

We also worked on improving digestion by removing food allergens, supplementing probiotics, and increasing stomach acid to help with the release of intrinsic factor. 

The patient was very compliant with the prescribed treatment plan and, after six months, we rechecked her levels expecting to see a substantial difference.  However, this was not the case. As her lab results had only slightly improved, it was clear something deeper was going on. 

I followed up by ordering genetic testing, looking specifically at genes associated with nutrient deficiencies.  The patient’s genotype came back homozygous for the risk allele (G/G) associated with B12 deficiencies in the FUT2-1 gene. This genotype is also known as a “secretor.”  As I looked deeper into this gene’s associated with B12 deficiencies, I ended up being reintroduced to the term secretor status. 

Long ago when I was researching the Eat Right for Your Blood Type Diet, a nutrition plan created by Dr. Peter D’adamo, I became aware of secretor status.  In this book dr. D’adamo crafted a diet plan that was based on a person’s blood type with the idea that the immune system of certain groups are more tolerant of foods that contain similar sugars as found on the red blood cells.  Another factor that affected a person was whether or not they were a secretor or a non-secretor, which means that they either secrete those sugars known as oligosaccharides that make up their blood type in the secretions, or they do not.   Secreting these sugars into the lumen of the gastrointestinal (GI) tract has a profound effect on the gut environment.  When I first read about this correlation, the connection with lowered plasma B12 levels was not clear.  But as I learned more about the mechanism of action behind this risk allele, I increased my understanding of the world inside the GI tract. 

In a 2008 study,  “Common variants of FUT2 are associated with plasma vitamin B12 levels,” authour Aditi Hazra. PhD, assistant professor at Harvard Medical School, and associates from the Harvard T.H. Chan School Of Public Health, reported that the secretor status, which was identified as the genotype (G/G or G/A) of the FUT2-1 gene, was associated with lower plasma B12 levels.  Non-secretors, however, do not show lowered levels of plasma B12. 

Absorption of nutrients is highly dependent on the types of bacteria living in the gut.  As these helpful inhabitants feed themselves, they create bi-products that nourish the epithelial cells of our GI tract.  In turn, we secrete the oligosaccharides that make up blood type in the secretions that line the intestines, feeding these beneficial bacteria and creating a better environment.

In a 2011 reprt, Pirjo Wacklin, PhD, researcher at Thermo Fisher Scientific in Waltham, Massachuetts, shows that that non-secretors had lower amounts of bifidobacteria.

In addition to influencing levels of beneficial bacterial, a secretor status can also affect the amount of harmful bacteria.  Having a non-secretor status has been reported to be protective from both norovirus and rotavirus, according to studies conducted in 2017 by Tu Li-Tzu of the Chang Gung University of Mediicine and in 2016 by Gokce Günaydın of Department of Laboratory Medicine, Division of Clinical Immunology and Transfusion Medicine, Karolinska Institute at Karolinska University. 

Another bacteria affected by the presence of blood type in GI secretions is h. pylori. In two studies authored in 2016 by Ana Magalhães from the Institute of Molecular Pathology and Immunology of University of Porto, and in 2015 by Shazia Akbar Ansari from the Immunology and Infectious Diseases Research Laboratory in the Department of Microbiology at the University of Karachi researchers showed non-secretors led to lowered levels of the pathogen in their digestive tract.  People who are non-secretors are more prone to diseases, such as Crohn’s, type 1 diabetes, experimental vaginal candidiasis, and urinary tract infections. 

Conversely, a more recent study conducted by W. Turpin from the Division of Gastroenterology in the Department of Medicine at the University of Toronto and associates reported no association between “secretor status and fecal microbial composition and inferred function in healthy subjects”.

How B12 levels are affected by the genotype is still up for debate. One idea says by affecting the composition of certain microbes, particularly h. pylori in the GI tract, this gene can influence the amount of B12 absorbed into the blood stream.  This can be useful information when developing a treatment plan.  By focusing on increasing serum B12 concentrations through intermuscular injections (IM), the practitioner can help patients with the secretor status to quickly replenish levels.  IM injections are great for this genotype because they by-pass the digestive system and allow the B12 to enter directly into the blood stream to be used by the body.

After weekly injections of methylcobalamin for five months, the patient mentioned earlier began to show great improvements in overall energy and health. Her CBC showed a mean corpuscular volume (MCV) value that was well within normal limits. 

A large part of the effectiveness of this treatment came from the patient’s wiliness to switch treatment modality once she understood her genotype and receive B12 injections. Knowing the underlying genetic architecture that plays a pivotal role in not only susceptibility to disease, but also responsiveness to certain treatments can greatly improve a practitioner’s ability to craft targeted treatment plans that bring about the strongest results.  

When a healthcare provider has a case that is non-responsive to standard treatment protocols, looking at the genetic code may provide the answer that is needed.