Vitamin B12: A Nutrient Shaped by Genetics & Microbes

Vitamin B12: A nutrient shaped by genetics & Microbes

Vitamin B12 is essential in various bodily functions, including energy metabolism, red blood cell production, and nerve function. Many factors influence the body’s ability to absorb vitamin B12. Genetics and the gut microbiome are among these factors. Both play a significant role in shaping our relationship with B12.

Genetic variations can affect how your body absorbs, utilizes, and metabolizes this nutrient. Certain gut bacteria can also produce B12, contributing to our overall B12 levels.

In our previous post, we have discussed how to monitor and manage vitamin B12 levels. Here, we’ll examine how genetic variations and gut microbiomes affect vitamin B12 absorption, utilization, and metabolism.

What is vitamin B12, and why do we need it?

As one of the most super important vitamins in the body, vitamin B12 plays a significant role in various biochemical reactions. Homocysteine metabolism, red blood cell production, DNA synthesis, and nerve function all depend on it. The amino acid homocysteine can damage blood vessels if it accumulates in high amounts. As a component of protein synthesis and cellular function, vitamin B12 helps convert homocysteine to methionine.

The human body does not produce vitamin B12, so it must be obtained from external sources, such as animal products (meat, eggs, dairy), fortified foods (cereals, pieces of bread, plant milk), or supplements. Some people may require more or less vitamin B12 depending on their age, health status, lifestyle, and genetic makeup.

How do genetic variations affect vitamin B12 levels?

Genetic variation is one of the internal factors that can affect the vitamin B12 level in our body. It is a change in the DNA sequence that can alter the function of genes or proteins.

Some genetic variations can affect the body’s ability to absorb, utilize, and metabolize vitamin B12. These are some examples of genes that affect vitamin B12 metabolism and how their variations can affect vitamin B12 levels:

FUT2:

Fucosyltransferase 2 (FUT2) encodes an enzyme that adds sugar molecules to intestinal cells. This sugar molecule acts as a receptor for intrinsic factor (IF), which binds vitamin B12 and facilitates its absorption in the small intestine.

Those with a variant of FUT2 that reduces or abolishes enzyme activity are called “non-secretors,” as their intestinal cells don’t secrete sugar molecules. Non-secretors have lower IF and vitamin B12 absorption levels than “secretors”, who have normal enzyme activity. A study found that non-secretors had 25% lower serum vitamin B12 levels than secretors.

TCN2:

The TCN2 gene encodes transcobalamin II (TCII), a protein that transports vitamin B12 from the intestine to the bloodstream and delivers it to the cells. People who have variants of TCN2 that reduce the amount or function of TCII have lower levels of circulating vitamin B12 than people with normal TCN2. In one study, people with a TCN2 variant had 31% lower serum vitamin B12 levels.

MTHFR:

This gene encodes an enzyme known as Methylenetetrahydrofolate reductase (MTHFR), which converts folate to its active form, 5-methyltetrahydrofolate (5-MTHF). 5-MTHF converts homocysteine to methionine, which requires vitamin B12 as a cofactor.

A person with a variant of MTHFR that reduces enzyme activity has a higher level of homocysteine and a lower level of 5-MTHF than a person with a normal MTHFR variant. This can impair the methylation cycle and affect the availability of vitamin B12 for other metabolic pathways.

According to a study, people with an MTHFR variant had 16% lower serum vitamin B12 levels than those without the variant.

MTR:

The gene encodes an enzyme known as methionine synthase (MTR), which converts homocysteine to methionine by using 5-MTHF and vitamin B12. Those with MTR variants that reduce enzyme activity have higher homocysteine levels and lower methionine levels than those with normal MTR. This can also affect the methylation cycle and the demand for vitamin B12.

A study found that people with an MTR variant had 14% lower serum vitamin B12 levels than people without the variant. However, in another study, the MTR variant was not associated with serum levels of vitamin B12. Much is still to be learned about how MTR variants affect serum vitamin B12 levels.

MTRR:

This gene encodes methionine synthase reductase (MTRR), an enzyme responsible for restoring vitamin B12’s active form in MTR. A person with a variant of the MTRR that reduces enzyme activity has lower levels of MTR activity and higher levels of homocysteine than an individual with a normal MTRR. As a result, vitamin B12 may become more necessary as the methylation cycle is impaired. A study found that people with an MTRR variant had 18% lower serum vitamin B12 levels than people without the variant.

NBPF3:

The gene encodes neuroblastoma breakpoint family member 3 (NBPF3), a DNA repair and chromatin remodeling component. A person with NBPF3 variants that increase this gene’s expression has higher levels of DNA damage and lower levels of vitamin B12 than one with NBPF3, which is normal. As a result, the genome’s stability and integrity and the cells’ functionality may be affected.

These are just a few of the genes that can affect vitamin B12 levels. Many more genes still need to be discovered or understood. Many factors can influence vitamin B12 metabolism, including genes and the environment. Hence, it is important to consider the individual’s genetic profile and context when assessing vitamin B12 status.

But it’s not just our genes that influence B12. It’s also influenced by our gut microbiome, the ecosystem of microorganisms in our digestive tract.

How does the gut microbiome affect vitamin B12 levels?

Several microorganisms live in the stomach and intestines, called the gut microbiome. Digestive health, immunity, and metabolism depend on these microorganisms. Several microorganisms can produce vitamin B12, which the host or other microbes may absorb.

There are, however, differences in the amount of vitamin B12 produced by different gut microbes. As with many things, some can produce more vitamin B12 than others, and some can produce different forms of vitamin B12, such as pseudovitamin B12, which is not biologically active in humans.

Factors Affecting Gut Microbiome: Shaping the B12 Landscape

Different factors, such as diet, antibiotics, probiotics, infections, diseases, and genetics, can influence the gut microbiome and its composition. These factors can affect how much and what type of vitamin B12 the gut microbes produce and how available it is for the host.

For instance, vegan diets that exclude animal products can reduce vitamin B12 intake from outside sources. It can generally encourage more vitamin B12-producing bacteria to populate the gut microbiome. Some people, however, may not be able to absorb or utilize vitamin B12 as efficiently because of genetic variations. As a result, vegans may need to take supplements or consume fortified foods to prevent a deficiency of vitamin B12.

Antibiotics are another example of drugs that kill or inhibit beneficial and harmful bacteria in the gut. As a result, the gut microbiome can be disrupted and produce less vitamin B12, affecting the body’s absorption ability. Therefore, people taking antibiotics may need probiotics or prebiotics to replenish their gut microbiome and prevent vitamin B12 deficiency.

What are other factors that influence vitamin B12 levels?

Vitamin B12 levels may also be affected by factors other than genetics and gut microbiome. The following are some of these factors:

Age:

The amount of stomach acid produced decreases with age, which is necessary for vitamin B12 to be release from food. They may also lack the IF or TCII necessary to absorb vitamin B12. Medications or chronic diseases may also interfere with vitamin B12 metabolism. It may be necessary for older adults to take higher doses of vitamin B12 to maintain adequate levels.

Sunlight exposure:

Skin synthesizes vitamin D with the help of sunlight, which is essential for bone and immune health. Additionally, vitamin D regulates the expression of genes related to vitamin B12 metabolism, such as TCN2 and MTHFR. Low vitamin D levels may impair these genes’ function and affect vitamin B12 status2.

Smoking:

Smoking increases oxidative stress and inflammation, damaging the cells and tissues that regulate vitamin B12. Also reduces vitamin B12 absorption from food and increases its excretion in urine. Studies have shown smokers may require more vitamin B12 than non-smokers to maintain adequate levels.

Physical activity:

Physical activity can influence vitamin B12 levels by influencing homocysteine clearance. A high level of homocysteine can cause cardiovascular problems. Vitamin B12 is necessary to convert homocysteine into methionine, which is essential for cellular functions and protein synthesis.

Moderate physical exercise increases blood flow and oxygen delivery to the tissues, which can lower homocysteine levels. However, excessive physical activity can increase homocysteine levels through muscle breakdown and tissue damage. Therefore, people who exercise regularly must balance their vitamin B12 intake with their physical activity levels.

Visit our previous post, “Why is vitamin B12 so important after bariatric surgery?” to learn more about other factors affecting vitamin B12 levels.

Conclusion

Vitamin B12 is a complex nutrient influence by internal and external factors. Genetic variations and gut microbiomes influence vitamin B12 absorption, utilization, and metabolism in the body. Understanding these complex interactions is essential for optimizing B12 levels and ensuring overall well-being.