Structure and functions
Vitamin B12 is called the "red vitamin" as it comes in the form of a crystalline compound with a bright red color. Vitamin B12 is the largest and most structurally complex B vitamin. Also known as "cobalamin", its chemical structure is formed by a ring with an atom of the mineral cobalt (Co) in the center, a biochemically rare element responsible for the intense coloration.
In addition to cobalt, cobalamin contains carbon (C), oxygen (O), phosphorus (P) and nitrogen (N); it is a water-soluble vitamin, stable to heat even if sensitive in heated acid or alkaline solutions; in fact, during cooking it can lose up to 70% of its activity while if exposed to light for prolonged times the loss of functionality occurs more slowly.
The main role of vitamin B12 is in the regulation of DNA synthesis and hemoglobin, promoting the formation and growth of red blood cells in the bone marrow. It also has a control action on the metabolism of the central nervous system, favoring the formation of the myelin sheath, the protein that surrounds and protects the nerve fibers, allowing a fast and appropriate conduction of the nerve impulse.
In the human body, cobalamin acts as a coenzyme (i.e. its presence is necessary for an enzymatic reaction to take place correctly) and intervenes in two important biochemical reactions: the first involves the transformation of methylmalonyl-CoenzymeA into succinyl-CoenzymeA, while the second conversion of homocysteine into the essential amino acid methionine. This latter reaction occurs in the presence of folic acid.
The two final products, succinyl-CoA and methionine, perform essential functions for the body. Succinyl-CoA is involved in the metabolism of fats and carbohydrates and in the process that leads to the formation of nucleotides, the building blocks necessary for DNA synthesis; methionine, on the other hand, is a sulfur amino acid (which contains sulfur, S) capable of lowering cholesterol levels in the body, protecting the kidneys, detoxifying the body from heavy metals as well as reducing the excessive accumulation of fat in the liver . Furthermore, it is proteinogenic as it intervenes in the synthesis of many proteins.
The discovery and subsequent isolation of cobalamin took place over 100 years, from the 19th to the 20th century. In the 19th century, people often died from pernicious anemia, a disease caused by metabolic dysfunction and vitamin B12 malabsorption. This anemia was characterized by an abnormal enlargement of red blood cells and for this reason also defined as "megaloblastic", often with a lethal outcome.
The term "pernicious", or malignant, incurable was given by the German internist Anton Biermer in 1872. During the nineteenth century, doctors observed that this form of anemia also presented a severe neuropathy initially called subacute combined degeneration: patients in fact showed neurological symptoms with disturbances of sensitivity, tingling and degeneration of the nervous circuits.
However, the mechanisms responsible for the neuronal degeneration associated with anemia were not yet clear at the time. Only at the end of the Great War was the correlation between pernicious anemia and diet discovered. In fact, patients subjected to a diet particularly rich in liver and red meat, even eaten raw, recovered and recovered from pernicious anemia. Only in 1948 it was possible to isolate from the liver the "therapeutic" factor which was given the name of vitamin B12 and in 1955 its chemical structure was definitively understood.
The causes of this form of anemia in adults were then clearly identified; it is in fact determined by the absence of the so-called Intrinsic factor (or Gastric antipernice, or Castle's), essential for the absorption of cobalamin (Extrinsic factor). The Intrinsic Factor is a glycoprotein secreted by some glands of the gastric mucosa: the loss of production of this substance is generally caused by the loss of the cells that produce it following autoimmune processes.
Intrinsic factor deficiency, with vitamin B12 deficiency have also been observed in people suffering from atrophic gastritis or gastrointestinal diseases such as Chron's disease, celiac disease, who have made prolonged use of antacid therapies or who have undergone surgery bariatric in case of severe obesity. There are also some cases characterized by genetic mutations in the metabolism of vitamin B12.
The human being is not able to produce vitamin B12, therefore he must take it from the diet; the absorption of cobalamin occurs at the level of the first sections of the intestine. In most cases, however, a vitamin B12 deficiency is related to insufficient dietary intake. The only organisms capable of producing vitamin B12 are some bacteria and archaea (the oldest microorganisms capable of surviving in extreme conditions).
Some of these bacteria have been found in the soil and grass that most ruminants eat; once ingested, these microorganisms proliferate and become part of the intestinal flora of animals, continuing to produce vitamin B12. Compared to most vitamins, cobalamin is mainly present in products of animal origin, which is why the deficiency is mainly associated with those who follow a vegetarian and vegan diet (unbalanced) or in those populations who, for socio-cultural reasons or poverty they do not have access to animal products.
Regardless of food choices, everyone should integrate cobalamin and, precisely because of the importance of its correct intake, vitamin B12 is now supplemented in industrial preparations (especially preparations based on breakfast cereals, bars, pasta and bread products. ) and also in some energy drinks (e.g. Red Bull and Burn).
The best sources of vitamin B12 are:
- Meat (especially liver, kidney and offal) of bovine, pork, rabbit
- seafood, especially mussels and crustaceans
- fish, and in particular tuna, cod, sardines, mackerel, salmon, mullet, trout
- milk and derivatives including yogurt, mozzarella, aged cheeses (parmesan, provolone, gruyere ...)
- fermented soy products, legumes
- products containing cyanobacteria, improperly defined blue algae (spirulina, klamath)
Vitamin B12 content in some foods and daily requirement
In Table 1 the micrograms (mcg) of vitamin B12 contained in 1 hectogram of the main foods that contain it are shown. The data are extracted from the IV Revision of the Reference Intake Levels of Nutrients and Energy for the Italian population (LARN) which represents the national document that the Italian Society of Human Nutrition (SINU) recommends to those involved in nutrition.
For those who choose to follow a strict vegetarian or vegan diet it is possible supplement vitamin B12 through fortified foods such as vegetable milks (soy, rice, almonds, coconut ...), cereals and breakfast products, soy and cereal-based products or through specific supplements of B vitamins or vitamin B12 supplements. As for ovo-milky vegetarians, they are able to supply adequate amounts of vitamin B12 from dairy products and eggs. In Table 2, SINU experts reported the vitamin B12 content in the foods that make up the vegetarian diet.
According to Table 3 of the SINU, for an adult (including women, men and adolescents aged 14 and over) the daily requirement is equal to 2 mcg while a quantity of 2.4 mcg per day is recommended. The recommended dietary intake known as RDA (Recommended Dietary Allowances) is slightly higher than the estimated average requirement in order to identify the quantities necessary to cover the needs of people with above-average needs. For pregnant and lactating women, the RDA should be increased (2.6 mcg and 2.8 mcg respectively). For children aged 1 to 14, the RDA increases with age from 0.9 to 2.2 mcg.
Normal and beneficial levels of Vitamin B12
In case of symptoms such as: tiredness, fatigue, tingling in the hands and feet, headache, mood swings, diagnosis of anemia or suspicion of malabsorption pathologies, the doctor may prescribe a test to monitor the levels of vitamin B12 by means of blood sampling. Normal levels of cobalamin in the blood are between 190 and 900 nanograms per milliliter (ng / ml).
The benefits listed here are all based on scientific studies. The use of the supplement alone is not able to cure pathologies and does not replace therapies. The intake of supplements should be associated with a correct lifestyle and a balanced diet together with the advice of your doctor.
It contributes to the prevention of malformations in the embryo and in the child
During gestation, a cobalamin deficiency can affect fetal development, very often resulting in the birth of underweight babies with probable growth delays. Vitamin B12 deficiency is often seen in pregnant women as their vitamin requirement increases; during the pre-birth period it is in fact recommended supplementation of vitamin B12 and folate.
Concerning the influence of vitamin B12 in the development of defects of the neural tube (the embryonic structure responsible for the formation of the central nervous system), opinions in the scientific world are still conflicting: it is yet to be demonstrated that a state of vitamin deficiency can determine failure to close the neural tube resulting in the birth of children with spina bifida. However, it is certain that the onset of a vitamin B12 deficiency in the first years of age causes brain damage with possible cognitive deficits and motor dysfunctions. Some studies have shown that already after the fourth month after birth, the concentration of vitamin B12 in breast milk is considerably reduced, causing a vitamin deficiency in infants fed with this food alone.
In the adult
Prevents neuronal loss
A vitamin B12 deficiency has been associated with memory loss or dementia in the elderly. Even in people with neurodegenerative diseases such as Parkinson's disease, Alzheimer's, multiple sclerosis and amyotrophic lateral sclerosis, cobalamin levels are altered. From studies still in progress it seems that vitamin B12 is able to prevent brain atrophy, or the loss of neurons in the brain.
According to a study in people with early-stage senile dementia, the combination of vitamin B12 supplements and omega-3 fatty acids slows cognitive decline. In any case, the integration of vitamin B12 in the elderly contributes to the improvement of memory, even in the absence of brain pathologies. Vitamin B12 is also able to improve mood, especially in those suffering from depression, as it is involved in the synthesis and metabolism of serotonin. In fact, a study showed that the administration of antidepressants together with a supplement of vitamin B12 significantly improved the symptoms of patients, compared to those who took only antidepressants.
Prevention of cardiovascular diseases
Low levels of vitamin B12 have also been detected in patients with cardiovascular diseases, therefore its integration can contribute to the prevention of vascular diseases such as atherosclerosis. As described in the first paragraph, vitamin B12 is able to convert homocysteine into the essential amino acid methionine. High blood homocysteine levels are associated with an increased risk of heart disease; consequently, in case of cobalamin deficiency, homocysteine levels become high. Proper vitamin supplementation helps reduce homocysteine levels.
Prevention of osteoporosis
Maintaining adequate levels of vitamin B12 contributes to the maintenance of a healthy skeletal system. A study conducted on about 2,500 adults has in fact shown that those with a vitamin B12 deficiency have a lower than normal bone density, with an increased risk of bone fractures as well as the development of osteoporosis.
Strengthening of the immune system
In people with cobalamin deficiency, a decrease in some cells of the immune system, particularly Natural Killer cells and CD8 + lymphocytes, has been observed. This discovery could have important implications in the treatment of diseases of the immune system.
Promotes healthy hair, skin and nails
Low cobalamin levels can be responsible for dermatological symptoms such as hyperpigmentation, nail discoloration with the appearance of white spots, hair alteration (excessive loss, thinning ...), vitiligo (loss of patchy skin color) and angular stomatitis ( annoying cuts in the corners of the mouth). The use of vitamin B12 supplements has shown a dramatic improvement in dermatological symptoms in people with vitamin deficiency.
Source of energy
All B vitamins play an important role in energy production. A deficiency of vitamin B12 is associated with tiredness and fatigue, therefore, taking a supplement can help you regain energy, especially in the change of seasons.
The era of nutrigenomics
In recent years, various researches have been developed in the field of nutrigenomics, i.e. the study of the correlation and interaction between the food we ingest and our DNA to understand if our eating habits influence the expression of our genes.
In fact, some researchers have shown that cobalamin has a genomic nutrient effect as it regulates the expression of genes and / or proteins in the central nervous system, liver, intestine and organs mainly involved in the intake of nutrients from food. The genes and proteins involved in this process are cytokines, growth factors and molecules related to the transport and metabolism of vitamin B12 itself. The data obtained are very valuable as they could lead, in the immediate future, to the development of new applications and therapeutic devices for those pathologies, such as tumors, in which it is necessary to modulate (switch on or off) the expression of some specific genes.
What vitamin B12 to take and in what form
Vitamin B12 consists of a class of chemically related compounds, called "vitamers", which have a physiological activity and are all presented as intense red crystals. Three of these vitamers are found in the food we ingest: Methylcobalamin (MeCbl), Adenosylcobalamin (AdCbl) and Hydroxocobalamin (OHCbl). AdCbl and OHCbl are the forms most contained in meat while MeCbl is commonly found in dairy products.
In other foods, these three forms of vitamin B12 are found in trace amounts or absent. Only MeCbl and ADCbl can be used by the human body as active coenzymes; AdCbl is found mainly in the body's reserves such as the liver and is active only within the mitochondria while MeCbl is found in the blood and spinal cord and carries out its activity in plasma cells. OHCbl is converted into the active forms through specific reactions.
In contrast, Cyanocobalamin (CNCbl) is a synthetic compound not found in nature, produced by companies to fortify some foods and in many supplements. CNCbl can only be found in small traces in human tissues as a result of cyanide intake from cigarettes. CNCbl is produced commercially via bacterial fermentation and is affordable.
Fermentation leads to the production of a mixture of the three forms described above: MeCbl, AdCbl and OHCbl. These 3 compounds are then converted to CNCbl by adding potassium cyanide in the presence of sodium nitrite and heat, which make the molecule very stable. Even the first three forms of cobalamin are now artificially produced together with CNCbl and are bioidentical to natural forms. Once introduced into the body, all 4 vitamers, taken through food or supplements, are reduced to cobalamin, then converted into the two active forms MeCbl and AdCbl in a proportion not affected by the ingested form of vitamin B12.
Furthermore, the cells convert vitamin B12 into the two active forms (MeCbl and AdCbl) using the methyl and adenosyl groups from other molecules and not from supplements consisting only of MeCbl or AdCbl. However, the bioavailability of any supplemented form of vitamin B12 can be influenced by several factors such as: gastrointestinal diseases, age and gene and protein mutations involved in the absorption of the vitamin. These mutations, called polymorphisms, can therefore alter the absorption, transport into the bloodstream, the uptake by the cells and the conversion of vitamin B12 into the active forms. There are currently no commercial tests available that identify mutations, justifying the use of one or more forms of vitamin B12. Finally, unlike the three natural vitamers, cyanocobalamin is the one that has shown the least absorption in the body.
Vitamin B12 is included in multivitamin pills, capsules, tablets or sachets (up to 1000 and, in some cases, 5000mcg per intake). It can also be found as a supplement in some grain-based food products such as bread and pasta. Some formulations such as injections and patches are used in cases where digestive absorption is compromised even if currently the oral supplements available on the market are characterized by high potency and effectiveness even in these cases. If genetic mutations have been identified with alterations of some metabolic pathways (for example homocysteinuria), intravenous, intramuscular or transdermal administration is necessary.
Excess of vitamin B12 and drug interaction
Currently there have been no toxic effects or adverse events in case of overdose of Vitamin B12. However, those who suffer from particular diseases for which they take certain drugs, must necessarily speak to their doctor before using cobalamin-based supplements. In fact, many drugs can affect the absorption of B12, causing a vitamin deficiency. These include: proton pump inhibitors such as omeprazole or lansoprazole, used for the treatment of gastroesophageal reflux and peptic ulcer; histamine H2 receptor antagonists such as ranitidine and cimetidine, used for peptic ulcer; metformin, a hypoglycemic agent for the treatment of diabetes.