What Does B₁₂ Do In Humans?

Vitamins are molecules that help the human body function properly. Vitamins help humans unlock energy, grow strong bones, and fight off germs. Many vitamins cannot be made by humans in sufficient amounts (or at all). So, humans need to consume vitamins from food sources to stay healthy.

B₁₂ is an important vitamin that has many roles in the human body. Deficiencies (low B₁₂) can cause a wide range of health problems (Figure 1). B₁₂ can protect cells from damage by harmful substances, and some research suggests that it might protect DNA—the “instructions” of the body that every cell needs to grow and divide properly [1]. Low levels of B₁₂ are associated with DNA damage and issues with how cells read certain parts of the DNA instructions used to make proteins (molecules that do work inside cells).

One of the most important things that B₁₂ does in your body is to help certain important proteins do their jobs [2]. When these proteins cannot function as they should, a lot of things can go wrong. You even might start to experience nerve and memory issues [1].

Everything in your body must be kept in the appropriate balance for you to be healthy. So, your body has a lot of processes (often carried out by different proteins) that work just to keep everything balanced. A special helper protein (called methionine synthase) needs B₁₂ to help it manage the levels of a chemical (called homocysteine) that can be toxic to your body in excess. Without B₁₂, methionine synthase stops working properly and homocysteine builds up in your body to toxic levels. This can increase your risk of heart disease, stroke, and blood clots [1].

On top of helping to balance things in your body, methionine synthase also helps to build your DNA. When it does not work due to low B₁₂, your red blood cells can grow too big and might not divide as they should. This can result in fewer healthy red blood cells that can deliver oxygen to wherever needed. This condition is called megaloblastic anemia, and it can make you feel weak, dizzy, and out of breath [2].

It takes a long time (a few years) of not getting enough B₁₂ before the negative effects start showing (Figure 1). Average healthy adults should have thousands of times more vitamin B₁₂ stored in their bodies than is lost through waste [1]. People can have low levels of B₁₂ for many different reasons. It can happen because their bodies cannot absorb B₁₂ well (common in older people), because they do not eat foods that are high in B₁₂ (common in vegans/vegetarians), or they might even be infected with organisms that use up their B₁₂. This can usually be resolved with B₁₂ supplements, commonly taken as pills, syrups, or injections [1].

What Does B₁₂ Do In Microbes?

Microbes are tiny organisms that can be found living together in interactive communities. Knowing which microbes need, want, or make B₁₂ can help scientists understand how they work together or compete. One way to predict who makes or needs what is to use genome sequencing, where scientists study DNA to predict what functions microbes may or may not be able to do, including making and using B₁₂.

Many microbes use B₁₂ for making DNA building blocks, making protein building blocks, using or getting carbon, and making energy via photosynthesis. In the ocean, most microbes are thought to use B₁₂, even though only a few of them can make it. Since so many microbes want it but cannot make it, B₁₂ can play a very big role in how these microbes live and interact with each other in communities. Some microbes exchange the B₁₂ they make for other nutrients that they might need [3].

Given that B₁₂ is a limited resource, some microbes can make two types of the same protein: one that needs B₁₂ to work, and one that does not [4]. If they have plenty of B₁₂ available, then they will use the B₁₂-containing proteins since they work best. But if B₁₂ is low, then they can switch to a different version of the protein that does not need the vitamin [3].

How Is B₁₂ Made In Microbes?

Making B₁₂ is a complex process that happens through a pathway, which is a series of chemical steps that work toward one goal (Figure 2). B₁₂ is one of the most complicated molecules that is naturally made. This pathway includes many different steps. At each step, a special protein is required to change the molecule into another form needed to feed into the next step.

Only a few types of microbes can make the proteins needed to complete all those steps. When scientists looked at more than 11,000 different species of bacteria, 86% were predicted to have some use for B₁₂, but only 37% were predicted to be able to make it on their own, while 17% were found to be able to do a few steps in the pathway [4].

The B₁₂ pathway can be simplified into three big parts. First, the early part of the molecule is made. Then, the process has two different ways to proceed: one branch that needs oxygen and one that does not. A metal (cobalt) is added, which helps B₁₂ function properly. In the last part of the B₁₂ pathway, both branches end up making the same molecule. From there, extra parts are sometimes added on, which can change the form of B₁₂ and impact how it is used, to fit the needs of certain proteins (Figure 2) [4].

Since the pathway is so complex, making B₁₂ takes a lot of energy, so some microbes have either stopped making B₁₂ completely or make only parts of it. Even bacteria that can make B₁₂ have ways to bring B₁₂ from the environment into their cells, meaning that they also might prefer to get the vitamin from the outside whenever they can, since it takes less energy [4]. Sometimes microbes find molecules in their surroundings from the middle of the B₁₂ pathway, so consuming them means that they can skip the first steps of the pathway. In some cases, two microbes can work together to make B₁₂ from scratch, each making one part of the molecule [5]. Still, making B₁₂ independently can be helpful, as those microbes do not have to rely on others or on their environment [4].

Scientists have capitalized on bacteria’s ability to make the complex B₁₂ chemical structure. Companies use bacteria that naturally make B₁₂ to produce B₁₂ supplements on a massive industrial scale. While scientists could make B₁₂ entirely synthetically (without microbes), the process would be very difficult and extremely expensive. Instead, companies primarily use microbes to make B₁₂–think of it as a big microbial farm where microbes are grown, the B₁₂ that they make is harvested, and the vitamin is then prepared as supplements to sell to customers. Companies rely on the same processes that happen in nature but apply it on a large scale for production.

How Do Humans And Other Animals Get B₁₂?

Animals like humans cannot make B₁₂ so they must rely on B₁₂-producing microbes [1]. Although there are helpful microbes in humans that can make B₁₂, they often make too little or make it in the large intestine where absorption is not the best. Other nearby microbes may compete for it as well, which lowers how much is available for human cells [1]. Instead, humans get B₁₂ from food sources that have built up B₁₂ made from microbes. For instance, microbes in the ocean make B₁₂, then small animals like krill eat the microbes and store the B₁₂ in their tissues (Figure 3). As larger animals eat the smaller animals, the B₁₂ levels gradually build up as it moves up the food chain to larger predators, including humans.

Most people get vitamin B₁₂ by eating animal products, particularly meat, milk, and fish. Animals like cows and sheep (called ruminants) usually have more B₁₂ than pigs and chickens. Ruminants have a special part of their stomach called a rumen, which contains microbes that can make B₁₂. This B₁₂ is then absorbed through the animal’s small intestine (Figure 1). Other animals that only eat plants, like rabbits, get B₁₂ by eating their own poop, which has B₁₂ from the microbes in their large intestines. Animals that eat meat and plants like pigs or chickens mainly get their B₁₂ from eating other animals [6].

Dairy products (including milk, yogurt, and cheese) are some of the most significant sources of B₁₂ in many cultures because they are consumed so often. The actual vitamin content of these products tends to be lower than that of the meat of the animal, and a lot of it can be lost during the production of these products. B₁₂ in milk can be lost to heat treatments (pasteurization), fermentation (producing foods like yogurts), and storage (due to light). Meat can also lose B₁₂ during the cooking process [7].

Plants do not make B₁₂, and they do not require B₁₂ helpers. If they contain any B₁₂ in their tissues, it is most likely due to interactions with microbes. B₁₂ deficiency can still negatively affect their growth if it affects the microbes that help them grow. Among plant-based foods, some dried seaweeds have been suggested as a good source of B₁₂ [7].

Conclusion

Ultimately, all the vitamin B₁₂ that humans and animals use comes from microbes. Even though only a small number of microbes can make B₁₂, they are extremely important for sustaining life on Earth. Without them, animals (and people) would not get the B₁₂ they need to stay healthy. The process of making B₁₂ is so difficult that sometimes microbes opt to divide and conquer and share different parts/stages of B₁₂ production between one another. By learning more about the broader ecological impacts of B₁₂, scientists can better understand food chains, protect ecosystems, and even find new ways to make B₁₂ in labs, which could help people who do not eat meat or have trouble absorbing vitamins. This one molecule made by tiny organisms has a tremendous impact on the world and its creatures.

Glossary

Vitamin: ↑ A nutrient that the body needs, in fairly small amounts, to work properly.

Molecule: ↑ Two or more atoms joined together (such as hydrogen and oxygen atoms joining to make water molecules).

Proteins: ↑ Big molecules made of amino acids (building blocks); some can help reactions happen.

Megaloblastic Anemia: ↑ A disease in which red blood cells are too big and do not work properly.

Microbes: ↑ Tiny living things that include microscopic bacteria, archaea, and eukaryotes.

Genome Sequencing: ↑ A laboratory technique used to read all the DNA of an organism.

Photosynthesis: ↑ A way in which organisms can get energy from sunlight.

Pathway: ↑ A step-by-step assembly line in which proteins convert molecules from one form to another inside cells.

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Conflict of Interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.