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Could Your Patients' Genes Be Impacting B12 Deficiency?

Vitamin B12, or cobalamin, is a water-soluble vitamin essential for DNA synthesis, red blood cell formation, and neurological function. Deficiency can lead to anemia, nerve damage, and cognitive issues, including memory loss. Those following a vegan or vegetarian diet, those with malabsorptive conditions, and older adults are typically at higher risk for deficiency. Often overlooked are the genetic variations that significantly affect B12 metabolism, influencing deficiency risk.

Vitamin B12 Metabolism Overview

B12 is bound to protein in foods like beef, salmon, tuna, milk, yogurt, eggs, etc. Once that food is mixed with saliva, it starts to free the B12 from the protein. Once in the stomach, hydrochloric acid and protease enzymes continue to free B12 until it can bind to intrinsic factor (IF), a glycoprotein produced by parietal cells. 

It then enters the small intestine, where receptors facilitate absorption. Once absorbed, B12 is transported to the liver and other tissues, where it serves as a cofactor in enzymatic reactions critical for DNA synthesis and myelin formation.

The B12 that is typically added to foods or used in supplement form is in its free form, not requiring the separation step. 

Genetic Variants Affecting B12 Metabolism

1. CUBN (Cubilin): CUBN encodes the intrinsic factor-vitamin B12 receptor, making it heavily involved in the absorption of vitamin B12. Polymorphisms in this gene have been associated with impaired B12 absorption thereby altering B12 levels and increasing risk of deficiency. 

2. FUT2 (Fucosyltransferase 2): FUT2 is responsible for synthesizing antigens on the surface of red blood cells and in secretions. Variants in FUT2 can affect the secretion of B12-binding proteins, influencing B12 bioavailability. Individuals with certain FUT2 mutations may have altered B12 absorption and transport, impacting their B12 status.

3. MTHFR (Methylenetetrahydrofolate Reductase): MTHFR is involved in folate metabolism and homocysteine regulation. Mutations in MTHFR can lead to reduced amounts of active folate and elevated homocysteine levels, which may interfere with B12 metabolism. 

Practical Application

Understanding these genetic variants is crucial for healthcare professionals in assessing B12 deficiency risk. Genetic testing can identify individuals with mutations in CUBN, FUT2, or MTHFR, allowing for personalized management strategies. 

For example, patients with CUBN mutations may benefit from higher B12 supplementation, while those with FUT2 mutations might require alternative forms of B12, such as methylcobalamin or adenosylcobalamin, that are more readily absorbed.

Summary 

Genetic factors play a significant role in Vitamin B12 metabolism, influencing absorption, transport, and utilization. By recognizing the impact of genes like CUBN, FUT2, and MTHFR, healthcare professionals can enhance diagnostic accuracy and tailor treatment plans to individual genetic profiles. Incorporating genetic assessments into clinical practice can lead to more effective management of B12 deficiency and its associated health risks.

If you're a healthcare professional, consider integrating genetic testing into your practice to better identify patients at risk for B12 deficiency. By understanding the genetic factors at play, you can tailor treatment plans and optimize B12 management for your patients.