Vitamin B12 is an essential vitamin for humans because our body cannot produce it by itself and must get it from food.
Vitamin B12, also called 'cobalamin', is the overall name given to four compounds (derivatives) that all contain the metallic element 'cobalt'.
The difference between the four cobalamin derivatives is in the type of molecule to which each derivative is attached. For example, binding to a methyl group creates the methyl-cobalamin derivative, binding to a cyanide molecule creates the cyano-cobalamin derivative, binding to an adenosyl molecule creates the adenosyl-cobalamin derivative and binding to a hydroxyl molecule creates the hydroxy-cobalamin molecule.
Of these four derivatives of vitamin B12, only the derivatives methyl-cobalamin and adenosyl-cobalamin have physiological activity in the body and are used as cofactors for two enzymes of critical importance in the human body.
Without methyl-cobalamin and adenosyl-cobalamin, two important enzymes could not function, which is also why vitamin B12 deficiency conditions can be dangerous.
In contrast, cyano-cobalamin and hydroxy-cobalamin are derivatives of vitamin B12 that are not physiologically active in the body. They can undergo enzymatic conversion processes in the cells to become methyl-cobalamin or adenosyl-cobalamin and only then be active.
For this reason, these derivatives are called 'pro-vitamins' (because they do not constitute active vitamins).
Which enzymes in the body depend on the active derivatives of vitamin B12, and what are the consequences of a deficiency in these derivatives?
The enzyme methionine synthase (MS) and the enzyme methyl malonyl-coenzyme A mutase (MUT) depend on the active derivatives of vitamin B12 and without them, they would not be able to function.
The enzyme MS is required to convert the amino acid homocysteine to the amino acid methionine. But in the case of a deficiency of vitamin B12 of the methyl-cobalamin type, the enzyme will not be able to function optimally, which will manifest itself in megaloblastic anemia, damage to the production of DNA, as well as a dangerous increase in homocysteine levels, which is linked to cardiovascular diseases. Methylcobalamin in combination with folate (natural folic acid) is also essential for the normal development of the brain during childhood.
The MUT enzyme also depends on active vitamin B12 for the metabolism of certain fatty acids. A lack of active vitamin B12 will damage the activity of the enzyme, and will eventually manifest itself in neurological symptoms, some of which are irreversible, in psychiatric disorders, a high rate of miscarriages, and a high incidence of birth defects in newborns.
Besides the great importance that the active derivatives of vitamin B12 have in the activation of the aforementioned enzymes, the active derivative methyl-cobalamin additionally participates in the methylation process (also called the 'methylation cycle'). Methylation has wide-ranging and very important physiological consequences on vital functions, such as the nervous system, the cardiovascular system, the immune system, energy production processes, maintaining hormonal balance, protecting DNA molecules, and more.
Vitamin B12 of the methyl-cobalamin type participates in the methylation process as a supplier of a very essential chemical group called the 'methyl group'.
The natural derivatives of vitamin B12 versus the synthetic derivative
Of the four derivatives of vitamin B12, there are 3 natural derivatives: methyl-cobalamin, adenosyl-cobalamin, and hydroxy-cobalamin, and one synthetic derivative: cyano-cobalamin.
The natural derivatives of vitamin B12 are found in food sources, mostly from animals. Animals store the three natural derivatives in milk, eggs, muscles, and especially in the liver.
For example, adenosyl-cobalamin is the derivative found in a high percentage of meat (68%), and the rest (32%) are the derivatives methyl-cobalamin and hydroxy-cobalamin. Methylcobalamin is found in the highest proportion in milk and eggs.
For this reason, both vegans and vegetarians are generally at high risk of developing vitamin B12 deficiency, even though the vitamin is also present in eggs and milk. This is because eggs and milk contain B12 in a relatively low amount and the absorption of the vitamin from them is also low.
In addition, processing processes of milk (such as heating and pasteurization) further reduce the amount of the vitamin.
As for plant foods, most of them contain a derivative of vitamin B12 that the human body cannot use and therefore it is called Pseudo Vitamin B12 (that is, "unreal" vitamin B12). This is especially true of many types of algae such as spirulina that contain vitamin B12 but is not biologically active.
Other vegetarian food sources often contain negligible amounts of B12 that do not meet the recommended daily intake (such as tempeh - which is made from fermented soybeans, shiitake mushrooms - which must be consumed in a huge amount to get the recommended daily intake, and algae such as chlorella - which have huge percentage differences between the various supplements Vitamin B12, as discovered in studies).
Cyano-cobalamin is a synthetic derivative that is not found naturally in food sources, and as mentioned, it is not physiologically active in the body, without a conversion process which we will detail later.
Absorption of vitamin B12 from food and supplements
The absorption of vitamin B12 from food is done in a very complex process, which may be damaged in various situations.
Let's start by saying that vitamin B12 from food comes bound to protein. Therefore, its bioavailability depends on sufficient secretion of stomach acid and various enzymes that release the vitamin from the food. After release, the vitamin binds to a component called haptocorrin that carries it along the digestive tract. When the vitamin reaches the absorption sites in the small intestine, it is released with the help of enzymes from the haptoglobin and binds to a protein called the 'intrinsic factor' which helps it go through the absorption process.
However, various health conditions can damage any of the steps in the absorption process of the vitamin, and as a result, the bioavailability of the vitamin in the body is also damaged. These conditions include autoimmune diseases that harm the secretion of the 'internal factor' (such as pernicious anemia and atrophic gastritis), and problems that harm the absorption functions of the intestine (such as celiac disease, ulcerative colitis, Crohn's disease), and also a decrease in stomach acidity as a result of old age or taking certain medications. Therefore, quite a few populations, apart from vegetarians and vegans, tend to be deficient.
Also in a very extensive epidemiological study conducted in the USA (known as the "Framingham study”), it was discovered that about 40% of the adult population is at risk of suffering from vitamin B12 deficiency due to various absorption problems.
Compared to vitamin B12 from food, vitamin B12 from nutritional supplements comes when it is not bound to protein, and therefore its absorption does not depend on stomach acidity and it does not even need the 'internal factor' protein for its absorption.
The differences between B12 in the various nutritional supplements
As mentioned, vitamin B12 deficiency is quite common, and it can cause serious health problems and symptoms, ranging from extreme fatigue and digestive problems to nerve damage and emotional symptoms such as depression and memory problems. For this reason, many people take vitamin B12 supplements to meet physiological needs and prevent deficiencies.
Most nutritional supplements in the world and Israel are based on one of the two derivatives of vitamin B12: methyl-cobalamin (the active natural derivative) or cyano-cobalamin (the synthetic derivative that is not present in food and is not active by itself).
This is because adenosyl-cobalamin and hydroxy-cobalamin derivatives are not stable enough as dietary supplements. On the other hand, the hydroxy-cobalamin derivative is a prescription medicine that can only be given by injection when needed. Today some studies have proven that taking vitamin B12 orally is equally effective as its injection, as a treatment for vitamin B12 deficiency.
what are the main differences between methyl-cobalamin and cyano-cobalamin?
While the methyl-cobalamin derivative contains a methyl group (the same valuable chemical group that is so important to the methylation processes), the synthetic cyano-cobalamin derivative contains a cyanide molecule.
Cyanide is a toxic molecule to the body. Therefore, the cyano-cobalamin derivative must be broken down in the body into two components: cyanide - which will be excreted from the body in the urine, and cobalamin - which will be converted into one of the two physiologically active co-factors (methyl-cobalamin or adenosyl-cobalamin).
But it is important to note that this breakdown of cyano-cobalamin may not be carried out due to genetic defects that exist in quite a few people in the healthy population, so in this case, the cyano-cobalamin supplement will not have a physiological activity in the body and will not be effective for the treatment or prevention of vitamin B12 deficiency.
Different researchers claim that this fact is not at all surprising, because cyanocobalamin is not a derivative of B12 that exists in nature, so it is expected that there may be genetic defects that will not allow its breakdown.
A study that compared taking a cyano-cobalamin supplement with a methyl-cobalamin supplement found that almost 3 times more cyano-cobalamin was excreted in the urine compared to methyl-cobalamin.
This result indicates that the assimilation in the body tissues of active vitamin B12 is more effective when taking the methylcobalamin supplement. In addition, it was found that taking methyl-cobalamin contributed to an increased storage of B12 in the liver, at a rate of 13% more than cyano-cobalamin.
Researchers who conducted a systematic review of studies also concluded from its results that taking any type of natural B12 supplement would be more effective than taking vitamin B12 of the cyano-cobalamin type. This is because of the increased excretion of cyano-cobalamin in the urine and the problematic nature of its bioavailability which results from poor absorption in the cells and problems in its metabolic activation For these reasons the researchers claimed that the cyano-cobalamin supplement is inferior compared to any natural and active derivative of vitamin B12.
The researchers who reviewed the aforementioned studies also expressed concern regarding the toxic accumulation of the cyanide molecule in body tissues, as a result of prolonged intake of a cyano-cobalamin supplement or frequent eating of food enriched with cyano-cobalamin. Also in a scientific article published in the prestigious journal The Lancet, a proposal was put forward to stop the use of cyanocobalamin in light of the problems arising from the cyanide molecule, in particular for smokers.
What are the potential clinical applications of taking methylcobalamin as shown by studies?
Facialis - the clinical findings showed that taking the methylcobalamin supplement dramatically improved the recovery time until normal nerve function.
In this study, the participants were divided into 3 groups:
group 1 was treated with steroids, group 2 was treated with methylcobalamin, and Group 3 was treated with a combination of methylcobalamin and steroids.
The results of the study showed that the time for full recovery and normal nerve function was the shortest in group 2, followed by group 3. The most severe score, as a measure of muscle function after 1-3 weeks of treatment, was given to group 1. In terms of the improvement in accompanying symptoms - the results were better in group 2 and group 3, compared to group 1.
Diabetic neuropathy - in this study, taking methylcobalamin for 4 months contributed to improving the symptoms of burning, numbness, muscle contractions, or loss of sensation in the limbs. In addition, there was an improvement in the reflex response, in the ability to feel a vibration in the test, there was an improvement in terms of muscle weakness and the feeling of sensitivity to pain
Visual functions - scientific experiments showed that long-term intake of methylcobalamin contributed to the protection of nerve cells in the retina from the toxicity of a component called glutamate (in a laboratory study in cells).
In addition, a clinical study found that deterioration in the ability to focus vision improved in people treated with methylcobalamin.
Changes in heart rate - changes in heart rate are an indicator of relative activity as well as a balance between the sympathetic/parasympathetic nervous systems. Methylcobalamin improved heart rate changes, indicating the modulating effect it has on the nervous system.
High levels of homocysteine - in a clinical study conducted in Japan, it was found that administration of methylcobalamin (by infusion) contributed to a significant reduction in blood homocysteine levels (from 14.7 to 10.2 nmol/ml) among type 2 diabetic patients diagnosed with small vessel disease.
The researchers concluded that high levels of homocysteine are a risk factor for the development of small vessel disease among type 2 diabetic patients and that methylcobalamin treatment can contribute to their reduction.
Improving sperm quality and quantity indicators in men - in a clinical study, administration of methylcobalamin at a dose of 6 mg/day for 16 weeks improved the sperm count by 37.5%.
In another study, the administration of methylcobalamin at a dose of 1500 mcg per lasting 4-24 weeks contributed to increased sperm concentration, sperm count, and sperm motility.
Sleep problems - the use of methylcobalamin for sleep-wake problems seems very promising. Although it has not yet been scientifically clarified in which mechanism methyl-cobalamin works in this context, there is a possibility that methyl-cobalamin is required for the production of melatonin (since the creation of melatonin requires the donation of a methyl group).
It seems that the addition of methyl-cobalamin has a high ability to influence the production of melatonin, increase sensitivity to light, and normalize the rhythms of the biological clock as well as the rhythms associated with sleep-wake.
Pain relief - a research review article found that taking methylcobalamin has the potential to significantly improve pain measures, such as pain associated with diabetic neuropathy, lower back pain, and neuralgia. In addition, methylcobalamin contributed to the improvement of nerve conduction and the recovery of damaged nerves.
ALS disease - in a recent phase II/III long-term clinical study, the effect of taking methylcobalamin at a high dose (25 mg or 50 mg) compared to taking a placebo, for 36 months or more, was examined among 373 ALS patients.
The researchers concluded from the results of the study that although the very high dose of methylcobalamin did not show significant effectiveness in all treatment groups, the results of the study show that this type of treatment, if started at an early stage, may extend the survival period of the patients and delay the progression of symptoms, and this without significant side effects.
Recommended Dosage:
The recommended dosage of methylcobalamin can vary depending on age, health conditions, and individual needs. It is best to consult with a healthcare professional to determine the appropriate dosage for you.
Side Effects and Precautions:
Methylcobalamin is generally considered safe and well-tolerated when taken within the recommended dosage. However, some individuals may experience mild side effects such as nausea, diarrhea, or allergic reactions.
If you have any pre-existing medical conditions or are taking medications, it's important to consult with your healthcare provider before starting any new supplementation.
Remember, this information is not a substitute for professional medical advice. If you have specific concerns about methylcobalamin or your vitamin B12 status, it is recommended to consult with a healthcare professional.