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Why Mecobalamin(co-methylcobalamin) and Hydroxocobalamin are superior forms of B12

Vitamin B12 supplements are typically derived from two sources: cyanocobalamin or methylcobalamin.

Both are nearly identical and contain a cobalt ion surrounded by a corrin ring.

However, each have a different molecule attached to the cobalt ion. While methylcobalamin contains a methyl group, cyanocobalamin contains a cyanide molecule. It also requires the presence of a cyanide molecule and while the amount of cyanide is not dangerous, it does require the body to expend energy to convert and remove it. The process used to detoxify cyanocobalamin could deplete glutathione reserves, a compound necessary for this detoxification. Cyanocobalamin must be detoxified, i.e. the cyanide must be cleaved off and the cobalamin portion must be attached to something else if it is going to work. This creates extra work for the body, making it more difficult to breakdown for those living with MTHR mutations.

Cyanocobalamin is an inactive, synthetic form of vitamin B12 that’s not found in nature.

While it is increasingly been considered the poorest, it is used more frequently in supplements as it is considerably cheaper than other forms of vitamin B12.

When cyanocobalamin enters your body, the body has to work much harder to be able to convert this form into the usable methylated B12's of methylcobalamin or adenosylcobalami. These are two active forms of vitamin B12 in humans.

Unlike cyanocobalamin, methylcobalamin is the methylated and naturally occurring form of vitamin B12 that can be obtained through premium supplements, as well as food sources like fish, meat, eggs, and milk. Methylcobalamin can be utilised by the body without requiring conversion and acts as a co-enzyme for the conversion of homocysteine to methionine. Aside from being synthetic, there is a growing body of research demonstrating lower tissue retention, higher urinary excretion, and, consequently, lower overall bioavailability of vitamin B12, supplemented in the form of CNCbl. Comparing the two forms reported that about three times as much cyanocobalamin was excreted through urine, indicating that methylcobalamin may be retained better within your body. This is an important aspect because the body stores cobalamin in the liver and it takes time for body to build up its surpluses, which it can take years to deplete. Methylcobalamin provides a universal methyl donor in various physiological processes, including DNA, RNA, histone, and protein methylation. Cyanocobalamin does not have the same methyl donating capabilities as methylcobalamin, additionally, some researchers suggest the use of natural vitamin B12 forms (hydroxocobalamin and mecobalamin) instead of cyanocobalamin for its long-term supplementations to avoid the accumulation of cyanide in human tissues.

Cyanocobalamin must be converted to methylcobalamin in the body before it can participate in these processes. Methylcobalamin and hydroxocobalamin are two forms of vitamin B12 that have gained attention for their potential health benefits. Both forms are known as "active" B12, meaning they are already in a form that the body can use, as opposed to "inactive" forms like cyanocobalamin, which must be converted by the body before it can be used. Adenosylcobalamin and hydroxocobalamin are the predominant forms of vitamin B12 (cobalamin) found in prepared foods. Hydroxocobalamin is the biologically active form of B12, meaning that it the B12 has already been converted into a form that your body’s methionine pathway can utilise immediately. Hydroxocobalamin is a nitric oxide scavenger that is well tolerated and detoxifies cyanide. When hydroxocobalamin is converted by the body into adenosylcobalamin and methylcobalamin, it is ready for the cells to absorb and use it. The main causes of B12 deficiency include inadequate dietary intake and malabsorption issues yet genetic predisposition to vitamin B12 deficiency has been demonstrated in various studies. B12 conversion can be a problem for people with MTHR, MTR and MTRR gene mutations. Also, individuals with COMT defects can be at higher risk for accumulating too much nitrous oxide or peroxynitrite which builds up in their bodies, causing stiffness and muscle pain or “brain fog” and cardiovascular problems. Hydroxocobalamin acts as a scavenger that can “mop up” the extra nitric oxide and peroxynitrites in the body and convert them back into methionine. This is very helpful especially for those suffering from Chronic Fatigue or Fibromyalgia. Some corners of the scientific world have been calling for the withdrawal of cyanocobalamin for therapeutic use with a particular emphasis on the fact that hydroxocobalamin and not cyanocobalamin is a powerful cyanide antagonist. Hydroxocobalamin has a longer half-life in the body compared to cyanocobalamin. This means it stays in the body for a longer period of time before being excreted, which allows for a slower and more sustained release of the vitamin into the bloodstream. This can be beneficial for individuals who have difficulty absorbing Vitamin B12 or have a long-term deficiency, as it allows for a slower, more consistent supply of the vitamin to be available for use in the body.

What is vitamin B12?

Vitamin B12, also known as cobalamin, is an essential nutrient that plays a critical role in many of the body's processes. It is involved in the production of red blood cells, the maintenance of nerve cells, and the synthesis of DNA and RNA. B12 deficiency can lead to a range of health problems, including anemia, nerve damage, and cognitive decline.

Methylcobalamin: an active form of B12

Methylcobalamin is a form of vitamin B12 that is already in a form that the body can use. It is known as a "coenzyme," meaning it helps enzymes function properly. Methylcobalamin is unique because it contains a methyl group, which allows it to participate in certain chemical reactions that other forms of B12 cannot.

One of the key roles of methylcobalamin is in the methylation process, which is the transfer of a methyl group from one molecule to another. Methylation is involved in a wide range of biological processes, including DNA synthesis and repair, immune function, and the regulation of gene expression. Methylcobalamin is also involved in the production of neurotransmitters, which are chemicals that transmit signals between nerve cells.

Hydroxocobalamin: another active form of B12

Like methylcobalamin, hydroxocobalamin is an active form of vitamin B12 that is already in a form that the body can use. It is also known as a coenzyme and is involved in several key processes in the body.

One of the primary roles of hydroxocobalamin is in the production of red blood cells. It is involved in the conversion of folic acid to its active form, which is necessary for the synthesis of red blood cells. Hydroxocobalamin is also involved in the metabolism of carbohydrates, fats, and proteins, and it plays a role in the synthesis of DNA and RNA.

The potential health benefits of methylcobalamin and hydroxocobalamin

Supplementing with any of the nature bioidentical forms of B12 (methylcobalamin, hydroxycobalamin, and/or adenosylcobalamin) is preferred instead of the use of CNCbl, owing to their superior bioavailability and safety.There is a growing body of evidence suggesting that methylcobalamin and hydroxocobalamin may have a range of potential health benefits. Here are a few examples:

Methylcobalamin and neuropathy

Neuropathy, or nerve damage, is a common complication of diabetes and can cause numbness, tingling, and pain in the hands and feet. Some studies have suggested that methylcobalamin may be effective in reducing the symptoms of neuropathy. For example, a study published in the Journal of Diabetes and Its Complications found that patients with diabetic neuropathy who were treated with methylcobalamin had significant improvements in nerve function and a reduction in pain.

Methylcobalamin and mental health

Methylcobalamin has also been studied for its potential effects on mental health. A review published in the Journal of Psychopharmacology found that methylcobalamin may have antidepressant and anxiolytic (anxiety-reducing) effects in people with depression and anxiety.

Hydroxocobalamin and anemia

Anemia is a condition characterized by a deficiency of red blood cells, which can lead to fatigue and other symptoms. Hydroxocobalamin has been shown to be effective in treating anemia caused by B12 deficiency. For example, a study published in the American Journal of Hematology found that patients with pernicious anemia (a type of anemia caused by a deficiency of B12) had significant improvements in hemoglobin levels and symptoms after treatment with hydroxocobalamin.

Hydroxocobalamin and detoxification

Hydroxocobalamin has also been studied for its potential role in detoxification. It is known to be effective in removing cyanide from the body, and it has been used in cases of cyanide poisoning. Some studies have also suggested that hydroxocobalamin may have a protective effect against the toxic effects of heavy metals, such as mercury and lead. 

What are the potential side effects of taking methylcobalamin and hydroxocobalamin supplements?

Methylcobalamin and hydroxocobalamin are a both forms of vitamin B12, also known as cobalamin, that are often used in supplements. They are generally safe to consume in recommended amounts. However, taking excessive amounts of either can cause side effects, including:

  • Digestive symptoms: Consuming large amounts of methylcobalamin can cause digestive symptoms, such as stomach cramps and diarrhea.

  • Skin reactions: Some people may develop skin reactions, such as rash or hives, after taking high doses of methylcobalamin.

  • Allergic reactions: Some people may be allergic to methylcobalamin. Symptoms of an allergic reaction may include rash, itching, and difficulty breathing.

  • Increased risk of certain cancers: Some research suggests that taking high doses of methylcobalamin and hydroxocobalamin may increase the risk of certain types of cancer, such as breast and prostate cancer. However, more research is needed to fully understand this relationship.

It is important to note that these side effects are typically associated with taking large amounts of methylcobalamin and hydroxocobalamin, well above the recommended daily intake. It is important to speak with a health professional before taking methylcobalamin and hydroxocobalamin supplements to ensure that you are taking the appropriate amount.

Methylcobalamin and hydroxocobalamin supplements are generally well tolerated and have a low risk of side effects. However, as with any supplement, it is important to speak with a healthcare professional before starting to ensure that they are safe and appropriate for you.

Can methylcobalamin and hydroxocobalamin supplements interact with other medications or supplements?

Yes, methylcobalamin and hydroxocobalamin supplements can interact with certain medications and supplements. Some medications and supplements that may interact with methylcobalamin include:

  • Chloramphenicol: This is an antibiotic medication. Taking methylcobalamin and hydroxocobalamin supplements along with chloramphenicol can interfere with the absorption of the antibiotic.

  • Proton pump inhibitors: These are medications that reduce stomach acid production, such as omeprazole and lansoprazole. Taking methylcobalamin and hydroxocobalamin supplements along with proton pump inhibitors can interfere with the absorption of the vitamin.

  • Metformin: This is a medication used to treat type 2 diabetes. Taking methylcobalamin and hydroxocobalamin supplements along with metformin can interfere with the absorption of the medication.

  • Colchicine: This is a medication used to treat gout. Taking methylcobalamin and hydroxocobalamin supplements along with colchicine can interfere with the absorption of both the medication and the supplement.

  • Other supplements: Some supplements, such as large doses of calcium and zinc, may interfere with the absorption of methylcobalamin and hydroxocobalamin. It is important to speak with a health professional about potential interactions between methylcobalamin and hydroxocobalamin and any other supplements you are taking.

It is important to speak with a health professional before taking methylcobalamin and hydroxocobalamin supplements to ensure that they are safe and appropriate for you. They can help you understand any potential interactions with other medications or supplements you are taking.

Is it safe to take methylcobalamin and hydroxocobalamin supplements if I have a particular health condition?

Vitamin B12, also known as cobalamin, is an essential nutrient that is necessary for various bodily functions. However, it is important to speak with a health professional before taking methylcobalamin and hydroxocobalamin supplements to ensure that they are safe and appropriate for you, particularly if you have a particular health condition. Some conditions that may be affected by methylcobalamin and hydroxocobalamin include:

  • Anemia: Vitamin B12 is necessary for the production of red blood cells. If you have anemia, taking methylcobalamin and hydroxocobalamin supplements may be beneficial. However, it is important to speak with a health professional about the appropriate amount to take.

  • Pregnancy: It is important to get enough vitamin B12 during pregnancy to support fetal development. However, taking excessive amounts of vitamin B12 during pregnancy may not be safe. It is important to speak with a health professional about the appropriate amount of vitamin B12 to take during pregnancy.

  • Malabsorption disorders: If you have a condition that affects your body's ability to absorb nutrients, such as celiac disease or inflammatory bowel disease, you may be at risk for a deficiency in vitamin B12. Taking methylcobalamin and hydroxocobalamin supplements may be beneficial in these cases, but it is important to speak with a health professional about the appropriate amount to take.

  • Kidney disease: If you have kidney disease, your body may have difficulty processing vitamin B12. This can lead to an accumulation of the nutrient in the body and potentially cause side effects. It is important to speak with a health professional about the appropriate amount of vitamin B12 to take if you have kidney disease.

It is always important to speak with a health professional before starting any new supplement to ensure that it is safe and appropriate for you.


In conclusion, methylcobalamin and hydroxocobalamin are active forms of B12 that are already in a form that the body can use. They have been shown to have a range of potential health benefits, including the treatment of neuropathy, mental health conditions, anemia, and detoxification. Vitamin B12 is especially important for vegetarians, vegans, and the elderly, as they may be at a higher risk of deficiency. 

It is worth noting that methylcobalamin and hydroxocobalamin supplements can be toxic in high doses. They may interact with certain medications or supplements, and they may have side effects in some people. If you are currently taking any medications or supplements, or if you have any underlying medical conditions, you should speak to your health professional before taking methylcobalamin and hydroxocobalamin or any other nutritional supplement. Your health professional can help you determine if methylcobalamin and hydroxocobalamin are safe and appropriate for you, based on your individual circumstances and medical history.


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