Skip to content
What's New? Dirty Genes -- The Histamine Workbook by Dr. Ben Lynch
What's New? Dirty Genes -- The Histamine Workbook by Dr. Ben Lynch

The Ultimate Guide to Vitamin B12: Forms, Benefits, Supplements, & More

The Ultimate Guide to Vitamin B12: Forms, Benefits, Supplements, & More

Written by: Elizma Lambert, ND

Vitamin B12 is an essential nutrient. Without enough, your entire body can suffer from symptoms. Low B12 impacts nerve cells, methylation, DNA health, mood, and your overall wellness. Vegans and vegetarians may not get enough vitamin B12 because it is mostly found in animal foods.

The good news is that you can get B12 from supplements. The bad news: B12 comes in several different forms. Assuming they are all the same is a common error.

In this article, we’ll explore the different forms of B12 and how their functions and benefits are different. You’ll learn why one type might work better for you and how to know you are getting enough. Plus, you’ll learn why gut health is an essential key to your optimal vitamin B12 levels.

What Is Vitamin B12?

What is B12

Vitamin B12 is an essential water-soluble B vitamin that is needed for many different functions in your body. It is the most complex of all vitamins when it comes to how your body stores and metabolizes this vital nutrient.

Vitamin B12 is chemically known as cobalamin. B12 is named cobalamin because it contains the mineral cobalt.

Different molecules attach to cobalamin, producing different forms of vitamin B12. These include:

  • Cyanocobalamin
  • Methylcobalamin
  • Hydroxocobalamin
  • Adenosylcobalamin

Each one has its own specific function. We’ll explore each one individually below.

What Does Vitamin B12 Do?

B12 is an essential vitamin with many functions in the body. You need it for normal biological and physiological processes like:

  • Biosynthesis of DNA
  • Healthy red blood cells
  • Maintenance of the gut mucosa and skin cells
  • Metabolism of fat, protein, and carbohydrates
  • Folate metabolism and the folate pathway
  • Formation of choline-containing phospholipids
  • Formation of succinyl coenzyme A which is needed for neural lipids and myelination
  • Maintenance of the myelin sheath that surrounds neurons and protects against nerve damage
  • Healthy energy levels

Most water-soluble vitamins are not stored in the body and must be regularly replenished. Vitamin B12 is a unique water-soluble nutrient. Your liver can store a substantial backup supply. That is how crucial B12 is to human health. Even though the liver can store it, vitamin B12 must still be regularly consumed. Low B12 levels can cause serious problems, but symptoms may take months or even years to show up. (1)

What Does Vitamin B12 Do

Vitamin B12 Food Sources

Vitamin B12 Food Sources

Vitamin B12 in any form does not exist in plants. Food sources of vitamin B12 include animal products like meat and dairy products. People who follow a vegan diet must supplement with this essential nutrient because it is not possible to get adequate amounts from whole plant-based foods alone.

Bioavailable B12 is found in many animal products, including:

  • Beef, lamb, and other red meat
  • Chicken and turkey
  • Liver
  • Dairy products
  • Eggs

Some plant foods do contain small amounts of inactive vitamin B12 forms known as B12 analogues. Others may have minute quantities of B12 derived from bacteria. These can include: (2)

  • Certain mushrooms
  • Chlorella supplements
  • Spirulina
  • Nori

Vegans commonly use nutritional yeast for B12. While it naturally contains other B vitamins, unfortified nutritional yeast does not contain vitamin B12. Only fortified nutritional yeast products contain B12.

The problem with natural vegan food sources of B12 is that they contain inactive forms of the nutrient. These less-bioavailable forms can be taken up and prevent bioavailable or active forms from being used. Even with a high intake of vegan-friendly “vitamin B12”, it is still possible to have low or deficient levels of vitamin B12. (2)

But eating B12 is not enough. Your body can only use it if your digestion and absorption are working. Because B12 exists in different forms, different enzymes are required for conversion and metabolism. There is an entire chain reaction that must take place to ensure that your body can use B12. It starts with digestion.

Digestion and Vitamin B12

Digestion and Vitamin B12

Whether you get B12 from animal foods, dairy products, vegan sources, or supplements, it must still be broken down and absorbed for your body to use it.

For that to happen, B12 must go through multiple steps. A problem at any part along the way can impact the bioavailability of vitamin B12.

  • Stomach: You need good stomach acid to digest animal proteins. This allows for the release of cobalamin, or B12, from these proteins. The process of producing acid/protons in your stomach cells takes a lot of energy and involves enzymes called ATP-ases. Regular or overuse of antacid medications such as proton pump inhibitors (PPIs)/ATP-ase inhibitors can negatively affect protein digestion and vitamin B12 absorption. Chronic stress, bacterial infections like Helicobacter pylori can all substantially reduce the production of stomach acid. As we age, our ATP levels often drop which will decrease our ability to produce acid as well. Without adequate acid to break down protein and release B12, your body cannot access this crucial nutrient. After the stomach acid does its work, B12 binds with haptocorrin proteins that reside in the stomach. These proteins help transport B12 to the small intestine.
  • Gallbladder: After stomach acid breaks down food into what is known as a bolus, it enters the small intestine. The low pH from all that acid, around 2, triggers the release of bile from the gallbladder. Bile is highly alkaline and increases the pH of the food bolus to being more alkaline, between 6.5 and 10. In an ideal pH environment, the B12 can release from haptocorrin and bind to an important protein called intrinsic factor. Without this step, the bolus would remain too acidic to bind with intrinsic factor, a protein that pairs with B12 so that the body can use it. Healthy bile formation is dependent on phospholipids, which can only be made if you have a functioning PEMT enzyme in the SAM pathway. (3) Interestingly, B12 is used as part of the process in making these phospholipids. By having a B12 deficiency, it may contribute to even less B12 being properly absorbed. 
  • Small intestine: After B12 binds with intrinsic factor, it travels further down the small intestine to the distal ileum. The B12 and intrinsic factor pair binds to the wall of the small intestine and releases the B12 into the bloodstream. Transcobalamin proteins then carry B12 in the blood plasma to be used by the body. These proteins include transcobalamin 1 (TCN1), 2 (TCN2) and 3 (TCN3).

Any problems with the small intestine can complicate this final step. This includes Celiac disease, Cystic Fibrosis, Crohn’s disease and any intestinal issue that degrades the intestinal lining. SIBO can also be a problem. Small intestinal bacterial overgrowth (SIBO) is a condition where bacteria that belong in the large intestine migrate to the small intestine. This disrupts the normal digestive process. With vitamin B12, some gut bacteria consume it while others produce it. In either case, the presence of large intestine bacteria in the small intestine can interfere with normal B12 levels.

Vegan Sources of B12

Common things that can negatively impact vitamin B12 absorption and transportation:

  1. Strict vegan diet
  2. Low stomach acid diet
  3. Pancreatic insufficiency
  4. Intrinsic factor antibodies
  5. Slow TCNs - Fortified foods with synthetic folic acid
  6. SIBO
  7. Celiac Disease
  8. Crohn’s

Vitamin B12 Supplements

Vitamin B12 Supplements

Vitamin B12 dietary supplements are very common. They are found in multivitamins, as part of B complex, or in standalone formulations. B12 may come in chewable gummies, liquid form, or lozenges. They are also available in the more traditional tablets and capsules.

When you look for a B12 supplement, there are many factors to consider. People want to make sure they get a good quality supplement, looking for one that is:

  • Gluten-free
  • Free from fillers
  • Non-GMO

But equally as important is the form of B12 that you take. The best vitamin B12 supplement for you depends on how readily your body can use the nutrient.

There are different forms of vitamin B12. As mentioned earlier, they are formed when cobalamin pairs with different molecules. Below we will explore each of the four types that are most commonly found in supplements.

Cyanocobalamin

Cyanocobalamin

Widely used in fortified foods, cyanocobalamin is a synthetic form of vitamin B12. It is often added to food products like cereals, bread, flour, baby formula, and more.

Cyanocobalamin is also the most common form of vitamin B12 found in supplements.  It is named because it contains a cyanide molecule. The amount of cyanide found in cyanocobalamin supplements tends to be small, but the body still has to do extra “work” to remove and eliminate the cyanide molecule. If your liver is already overworked, this added step can make activating this nutrient more challenging.

What Does Cyanocobalamin Do?

Cyanocobalamin can be converted to 5-deoxyadenosylcobalamin and methylcobalamin in the body. It is less expensive than other forms of B12 which is why it is commonly used by both food and supplement manufacturers.

Once cyanocobalamin has been converted, it can be used to support neurological health, methylation, DNA synthesis, and more. But for people who have SNPs in methylation-related genes, like MTHFR, they may be unable to efficiently convert cyanocobalamin to usable forms. This could result in low bioavailable levels even if intake of cyanocobalamin meets or exceeds the recommended daily amount.

Do You Need Cyanocobalamin?

You need vitamin B12, but you do not specifically need it in cyanocobalamin form. You do need bioavailable active forms of vitamin B12 like methylcobalamin, adenosylcobalamin, or hydroxocobalamin.

Methylcobalamin

Methylcobalamin

Also known as active B12, methylcobalamin is cobalamin that has paired with a methyl group.

Methylcobalamin is considered to be the most bioavailable form for methylation. This can vary depending on factors like genetics, digestion and stomach acid secretion, as well as current vitamin B12 levels.

What Does Methylcobalamin Do?

Methylcobalamin facilitates the following reactions:

  • Works with folate to convert homocysteine to methionine, which is needed to make S-adenosylmethionine (SAM). SAM is necessary for the methylation of various biochemical reactions, including myelin production. It is also necessary for the creation of some neurotransmitters and for brain and nervous system function.
  • Crosses the blood brain barrier to participate in methylation reactions in the brain. Brain function relies on the SAM pathway that involves MTR function.
  • Helps regenerate tetrahydrofolate (THF) which is necessary for DNA synthesis.

Do You Need Methylcobalamin

Do You Need Methylcobalamin?

Your body requires some form of bioavailable B12. You may need methylcobalamin if you are deficient in methyl-groups. You may also benefit from it if you are looking for extra support for your folate pathway. This could occur from long-term folic acid supplementation, as well as for other reasons.

By supplementing with methylcobalamin, you will add the essential methyl-group to the SAM pathway that methylated folate may not be able to provide.

Adenosylcobalamin

Adenosylcobalamin

Adenosylcobalamin is one of the main types of B12 that is naturally found in animal protein. (4) It is an active form of B12. It may also be referred to as:

  • Dibencozide
  • Adeno B12
  • Coenzyme B12

Adenosylcobalamin helps fuel cellular energy production. Without adenosylcobalamin, symptoms of tiredness or fatigue may be common.

What Does Adenosylcobalamin Do?

It helps make cellular energy by facilitating the following process:

  • Coenzyme A mutase (MUT) reactions help remove methylmalonic acid (MMA) and convert it to succinyl CoA. Succinyl CoA is used by the mitochondria, the energy factories of cells.

What Does Adenosylcobalamin Do

If you do not have enough adenosylcobalamin, you may have lower levels of succinyl CoA, which could lead to reduced energy or ATP production. This can lead to a deficiency in Complex II of the mitochondrial electron transport chain, which generates reactive oxygen species (ROS). These ROS can lead to more fatigue, inflammation, and dysfunctional cellular energy production.

Adequate access to adenosylcobalamin helps to ensure healthy levels of MMA in the body, supporting the health of the protective myelin sheath around nerves.

Do You Need Adenosylcobalamin?

Adenosylcobalamin may be beneficial if you want to support:

  • Nerve and nervous system health
  • Feelings of strength
  • Healthy energy levels
  • Healthy inflammatory processes

Hydroxocobalamin

Hydroxocobalamin

Hydroxocobalamin is the other main form of B12 that is naturally found in animal proteins. (4) It is an active, bioavailable form of B12 that may also be called hydroxycobalamin or hydroxy B12. Hydroxocobalamin has the longest half-life of any vitamin B12 form in the body. 

Hydroxocobalamin is a good alternative for people who react to methylcobalamin or adenosylcobalamin. Hydroxocobalamin is typically the form that is used in intramuscular B12 injections.

While hydroxocobalamin is not already methylated, it is readily converted to this form to support the methylation cycle. It can also convert to adenosylcobalamin to facilitate conversion of fats and amino acids to ATP. The body decides where hydroxocobalamin is needed most and converts it accordingly.

What Does Hydroxocobalamin Do?

Hydroxocobalamin is known to support the normal reduction of three important compounds:

  • Nitric Oxide (NO)
  • Hydrogen sulfide (H2S)
  • Cyanide

It does this by binding to these compounds and then eliminating them from the body.  Both nitric oxide and hydrogen sulfide do have important roles to play in your health. But excessive levels may not be beneficial especially under certain conditions.

What Does Hydroxocobalamin Do

  • Excessive nitric oxide levels may react with superoxide to produce peroxynitrite. Superoxide is a free radical produced by the immune system during infections. Like all free radicals, it can become problematic when produced chronically and in excessive amounts. Peroxynitrite is even more harmful than superoxide and can cause significant problems. Nitric oxide is often too high in those with inflammation, chronic infections, and low glutathione.
  • Excessive hydrogen sulfide may contribute to sulfur intolerance, diarrhea, migraine, sulfur-smelling stool, flatulence, bad breath, body odor, nausea, breathing problems, fatigue, poor memory, dizziness, and irritability. Hydrogen sulfide is produced as a product of normal cellular metabolism by the CBS and CTH enzymes. These enzymes work faster in the presence of oxidative stress or infections, which increases the need for hydroxocobalamin.

Do You Need Hydroxocobalamin?

Hydroxocobalamin supports healthy levels of nitric oxide, hydrogen sulfide, and cyanide. You may benefit from hydroxocobalamin if you show signs of high nitric oxide or hydrogen sulfide.

Symptoms of High Nitric Oxide levels

Symptoms of High Hydrogen Sulfide levels

  • Low blood pressure
  • Fatigue
  • General muscle discomfort
  • Dizzy upon standing
  • Headache
  • Low blood pressure
  • Fatigue
  • Brain fog
  • Irritability
  • Migraine
  • Headache
  • Asthma
  • Difficulty breathing
  • Dizziness
  • Diarrhea
  • Sulfur smelling gas, breath, stool and/or body odor

More is not always better. You need B12, nitric oxide, and hydrogen sulfide in balance. Extremely elevated amounts of  hydroxocobalamin may contribute to lower levels of nitric oxide and hydrogen sulfide.


Symptoms of Low Nitric Oxide levels

Symptoms of Low Hydrogen Sulfide levels

  • High blood pressure
  • Cold hands and feet
  • Erectile dysfunction
  • Difficulty breathing
  • Chest tightness
  • Inflammation

People who have reactions to sulfur-based supplements or foods may find that hydroxocobalamin is the form of vitamin B12 that works best for them. Since sulfur-based supplements and foods can increase hydrogen sulfide gas, hydroxocobalamin can help bind and reduce the excessive hydrogen sulfide.

In the same way, hydroxocobalamin can help with sensitivity to L-methylfolate (L-5MTHF). Because L-5MTHF may contribute to higher nitric oxide levels, hydroxocobalamin may help to maintain normal levels of nitric oxide. There are other reasons why someone may react to L-5MTHF, and hydroxocobalamin does not address all of them.

Vitamin B12 Safety and Side Effects

Vitamin B12 Safety and Side Effects

Vitamin B12 supplementation is generally safe and frequently recommended. It is safe during pregnancy and breastfeeding. Vegans and vegetarians are also frequently encouraged to supplement with B12 since their dietary intake is often inadequate.**

The RDA for vitamin B12 is 2.4 micrograms (mcg) for adults, 2.6 mcg for pregnancy, and 2.8 mcg during lactation. There is no tolerable upper limit for vitamin B12.  Even when consumed in large quantities, the potential for toxicity is low because the body does not retain most B12 that is consumed. (5)

Vitamin B12 deficiency is far more common than having too much B12.

Testing for Vitamin B12 Levels

Lab tests to assess vitamin B12 status are not as straightforward as other nutrients. Vitamin B12 is used within cells to carry out its biochemical actions. Serum B12 measures the B12 that circulates outside of the cells and not what is in the cells. Serum lab results can indicate a normal or elevated range and a person could still have low B12 levels within their cells. 

For a full picture, other labs may be run in conjunction with serum B12 to indicate cellular activity of B12. These include:  

  • Methylmalonic acid (MMA)
  • Homocysteine
  • Mean corpuscular volume (MCV)

When a healthcare professional tests B12 with these other labs, they can get a more detailed picture of whether your body shows signs of having enough accessible B12 or not.

Vitamin B12 and Gut Health

Vitamin B12 and Gut Health

It is not enough to eat or take vitamin B12. Your body cannot use this vital nutrient if it cannot break it down and absorb it. You need a well-functioning stomach and small intestine to digest and absorb the B12 that you consume.

Gut health influences vitamin B12 levels and test results in some specific ways.

Certain types of bacteria in the large intestine and colon can make vitamin B12, but the body’s B12 transporters are in the small intestine. So the B12 that your large intestine makes nourishes the microbiome, not the rest of the body. (6)

This is where gut health issues can cause problems. With SIBO, B12 made by the bacteria in the large intestine can migrate to the small intestine and get picked up by B12 transporters. The result is serum elevations of vitamin B12 that make it seem like you are getting enough from your diet or supplements when you are not.

On the other hand, in some cases of SIBO, bacteria from the large intestines travel back into the small intestines. Some bacteria that migrate to the small intestine are B12 consumers/“stealers”. Instead of inflating your B12 levels, they can consume the B12 from your small intestine that is needed for the rest of the body. This can lead to a vitamin B12 deficiency even if you eat or take adequate amounts. (7)

The Bottom Line

Vitamin B12 is a crucial nutrient for human health. While research agrees that every human needs it, the different forms and how the body puts it to use means that it’s not always simple to make sure you are getting what you need.

You can support optimal B12 levels by eating a diet that is rich in animal-based foods and by supplementing with bioavailable forms—especially if you follow a vegan or vegetarian diet.

For healthy B12 levels, your body also needs to be able to digest and absorb B12. Digestive and gut health are essential so that your body can use B12 for healthy cells, DNA, nerves, and much more.

 ** This information is for educational purposes only. As a supplement company, Seeking Health cannot dispense medical advice or answer any medically related questions. Always consult with your healthcare professional.

References

  1. https://www.ncbi.nlm.nih.gov/pubmed/28722952
  2. http://dx.doi.org/10.3390/nu6051861 
  3. http://dx.doi.org/10.1136/jcp.24.3.239
  4. http://dx.doi.org/10.1079/bjn19760063
  5. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/#h4
  6. http://dx.doi.org/10.1016/j.cmet.2014.10.002
  7. http://dx.doi.org/10.7554/eLife.37138 

Leave a comment

Comments must be approved before appearing

* Required fields

These statements have not been evaluated by the Food and Drug Administration (FDA). This product is not intended to diagnose, treat, cure, or prevent any disease.