What is vitamin B12 explained
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What are vitamins and their different solubility types?
Vitamins are a group of essentialmicronutrients that arerequiredfor maintaining normal cell function, growth, reproduction, development and various metabolic functions in our bodies.Although vitamins are needed in very small quantities, our diet must contain them so that the above mentioned critical functions can be seamless.Generally, vitamins are classified as fat-soluble or water-soluble types.The 13 essential vitamins are listed below.
Of these vitamins, eight of them belong to the vitamin B class often referred to as B complex, which includes vitamins B1, B2, B3, B5, B6, B7, B9 and B12. Vitamin B complex together with vitamin C are known as the water-soluble vitamins which are typically peed out when you get an excess of them (so considered less concerning when taking larger doses), while vitamins A, D, E and K are the fat-soluble vitamins which require you to be more careful so as not to get an excess build-up of them in your body.
- Vitamin A (Retinol and Antixerophthalmic vitamin)
- Vitamin B1 (Thiamine and Aneurin)
- Vitamin B2 (Riboflavin, Riboflavin-5-Phosphate and Vitamin G)
- Vitamin B3 (Niacin and Nicotinamide)
- Vitamin B5 (Pantothenic acid)
- Vitamin B6 (Pyridoxine and P-5-P)
- Vitamin B7 (Biotin and Vitamin H)
- Vitamin B9 (Folic acid, Folate and Methylfolate)
- Vitamin B12 (Cyanocobalamin, Hydroxocobalamin, Methylcobalamin, Adenosylcobalamin and anti-pernicious anemia factor)
- Vitamin C (Ascorbic acid)
- Vitamin D (Vitamin D2: Ergocalciferol and Vitamin D3: Cholecalciferol)
- Vitamin E (Alpha tocopherol)
- Vitamin K (Antihemorrhagic factor and Phytonadione)
What is vitamin B12 andwhatfoods can I find it in?
The food sources of vitamin B12 are fish, meat, eggs, organ meats such as liver and kidney, poultry, shellfish, milk and milk-derived products, as well as fortified foods like breads, cereals and boxed milks (i.e. soymilk). Vegetarian food contains only a very miniscule amount of vitamin B12. Plants do not absorb cobalamins from the soil.
As a result, vegetable sources essentially do not have vitamin B12.However many bacteria and algae do produce cobalamins. Consuming milk, dairy and soy products in large quantities would be mandatory just to attain the daily B12 requirement because the occurrence of vitamin B12 is very low in milk and soy products (so this is not considered the best option for B12 absorption). Besides natural sources, fortified foods can be considered to get a source of vitamin B12 into one’s diet.
However, it’s well worth noting that vitamin B12 in the fortified foods is solely in the cyanocobalamin form, which is not well absorbed by most individuals, not to mention it contains cyanide.The microorganisms present in the intestinal tract of the human body can only synthesize a little amount of vitamin B12. Vitamin B12 is really best absorbed via the mucous membrane in the mouth (typically by placing the B12 source under the tongue).
Different activity levels in four forms of vitamin B12
Vitamin B12 exists in four different forms such as cyanocobalamin, methylcobalamin, adenosylcobalamin, and hydroxocobalamin (the chemical structures of the different forms of vitamin B12 are displayed in figure 1 below). Of these four forms, all of them except cyanocobalamin, are bioactive, easily absorbed, and able to positively affect health.
Cyanocobalamin, however, isthe opposite and not so easily absorbed. All four of these forms contain cobalt metal atoms and thus collectively are referred to as cobalamins. Cobalamin consists of a heme-like planar corrin ring structure where four pyrrole nitrogens are coordinated to the central cobalt atom.
Methylcobalamin occurs naturally in the body and assists in producing red blood cells, DNA and takes part in other physiologic functions. It is known to actively participate in the methylation cycle in the body, as well as support folate and methionine metabolism.
It can be found in injection form or as an oral dietary supplement (look for a sublingual or chewable source that you can put under your tongue to dissolve for optimal absorption). It’s been determined through recent studies that intra-muscular and oral B12 absorption are both equally effective for the body.
Figure 1. Different forms of Vitamin B12 and their chemical structures
Adenosylcobalamin, an unstable molecule, exists naturally, is required for energy metabolism, and is harder to find in vitamin B12 supplements (it is more rare and expensive). It is often used by athletes in sports recovery.
Another natural form of vitamin B12 is hydroxycobalamin (or hydroxocobalamin), it’s considered the most well-tolerated form of all the active cobalamins. It’s also known for helping pernicious anemia. It is produced by the bacteria present in the digestive tractand is also available in both injectable and oral forms (the easiest way to take it is in a chewable/sublingual tablet – put it under the tongue for maximum absorption).
Hydroxycobalamin not only has its own mechanism of action within the body as a scavenger of nitric oxide, but it is also readily converted into the active forms, adenosylcobalamin and methylcobalamin, inside the body.
Cyanocobalamin is an artificial form of vitamin B12 containing a cyanide molecule that can be converted into the active form, hydroxocobalamin once inside the body, but only by some people. Many have genetic mutations on theMTR (methionine synthase) and MTRR (methionine synthase reductase) SNPs (single nucleotide polymorphisms) who can’t make this conversion very well and it affects the absorption of cobalamin in the body.
Cyanocobalamin is cheap and the most common form of B12 found in oral, intramuscular and intravenous vitamin B12 supplements, yetis known to be the least effective form for addressing B12 deficiencies.
How vitamin B12 is absorbed?
The absorption of vitamin B12 or cobalamin begins with its separation from food protein by the action of hydrochloric acid in the stomach. Haptocorrin, a transcobalamin protein also known as R-binders, is bound to the free cobalamin to protect it from the acidic environment of the stomach.
In the duodenum, haptocorrin is digested by pancreatic proteases and releases cobalamin which in turn gets attached to the intrinsic factor, a glycoprotein secreted by parietal cells of the gastric mucosa. The intrinsic factor-cobalamin complex travels up to the distal ileum where it binds to its specific cubilin receptor. Eventually, the complex is internalized and cobalamin is released into the bloodstream by lysosomes.
Of note, appropriate amount of intrinsic factor availability and optimal intestinal condition do not guarantee better absorption of vitamin B12, rather poor absorption through gut route is the outcome. For instance, 1000 microgram oral supplement of vitamin B12 results in the absorption of 20 microgram, therefore the absorption via gastrointestinal tract is around 2 percent.
On the another hand, sublingual vitamin B12 tablets are absorbed through the mucous membrane, and are able to reach blood circulation without entering into gastrointestinal tract. The sublingual route of vitamin B12 provides a greater absorption rate and is much less expensive when compared to intravenous vitamin B12 formulations (the other non-gut absorption mechanism).
Dosage of vitamin B12
The Food and Agriculture Organization of the United Nations and World Health Organization (FAO/WHO) consultation experts on human vitamin and mineral requirements reviewed the recommendations for an estimated average requirement and recommended nutrient intake of vitamin B12as shown in the table below.
| Age | Estimated average requirement (mcg) | Recommended nutrient intake (mcg) |
|---|---|---|
| 0–6months | 0.32 | 0.4 |
| 7–12 months | 0.32 | 0.5 |
| 1–3 years | 0.7 | 0.9 |
| 4–8 years | 1.0 | 1.2 |
| 9–13 years | 1.5 | 1.8 |
| >14 years & Adults | 2.0 | 2.4 |
| Pregnant women | 2.2 | 2.6 |
| Breast–feeding women | 2.4 | 2.8 |
The activeforms of vitamin B12-methylcobalamin, hydroxocobalamin, and adenosylcobalamin have been commercially available, and are preferred over cyanocobalamin because they are bioidentical forms occurring in human physiology and animal foods.
A comparative animal study on the effectiveness of methylcobalamin and cyanocobalamin supplementation has reported that urinary excretion of cyanocobalamin was 3 times higher than that of methylcobalamin (indicating it was less used by the body than the methylcobalamin). Methylcobalamin supplementation also resulted in 13% more cobalamin storage in the liver than that of cyanocobalamin.
Another study has also reported lower tissue retention and higher urinary excretion from cyanocobalamin supplements as compared to methylcobalamin, hydroxycobalamin, and adenosylcobalamin. Methylcobalamin is the most cost effective active form of natural B12 available at present in most of the multivitamins and B-complex formulas. But hydroxycobalamin is considered the most well-tolerated (even though it’s more rare and costly).
Key functions of vitamin B12
Vitamin B12 is a vital nutrient required to produce red blood cells, regulate the formation of the myelin sheath whichshields the nerve cells of the nervous system and facilitates the synthesis of DNA. It’s important to note that vitamin B12 helps in the prevention of pernicious anemia, hence, it is otherwise known as the “anti-pernicious anemia factor” (particularly the hydroxycobalamin form).
Vitamin B12 acts as a cofactor in two enzymes such as methionine synthase and methylmalonyl-coenzyme A mutase, which are critical enzymes in the production of SAMe (or S-adenosyl methionine), hemoglobin and catalytic intermediate by-products involved in fat and protein metabolism.
Vitamin B12 exists internally in two forms which are important to methylation, methylcobalamin and 5‑deoxyadenosyl cobalamin. Methylcobalamin acts as a cofactor for the enzyme methionine synthase, which converts homocysteine to methionine (this is important for the people who have high homocysteine). The converted methionine is useful for methylation of DNA.
Methylmalonyl-coenzyme A mutase enzyme requires 5‑deoxyadenosyl cobalamin as a cofactor for the conversion of l‑methylmalonyl CoA to succinyl CoA, which is an important step for producing energy from proteins and fats. Succinyl CoA is also essential for the production of hemoglobin.
Vitamin B12 deficiencies are very common; however, they are typically left undiagnosed,which meansthe deficiency usually remainsuntreated. The symptoms of a B12 deficiency vary from non-specific clinical features to severe neurological manifestations.
The deficiency of vitamin B12 can cause fatigue, bone marrow suppression, megaloblastic anemia, abnormal erythropoiesis, skin hyperpigmentation, palpitations, glossitis, and infertility.
Chronic deficiency causes progressive demyelination of nerve cells, peripheral neuropathy, areflexia, dementia and even psychosis in elderly patients. Vitamin B12 plays a profound role in a few major disorders - we’ll discuss more below.
Vitamin B12 and pernicious anemia
One of the important causes of vitamin B12 deficiency is pernicious anemia where absorption is severely reduced due to the lackofintrinsic factor. Pernicious anemia is an auto-immune disease, caused by the following factors.
- Antibodies generated against parietal cells which create atrophy of parietal cells that negatively affect the production of the intrinsic factor as well as hydrochloric acid.
- Auto-antibodies bind with intrinsic factor and avoid the formation of intrinsic factor – vitamin B12 complex. In this case, the parietal cells remain intact.
- The binding of vitamin B12 to the intrinsic factor is not inhibited, however, the antibodies disrupt the absorption of vitamin B12 – intrinsic factor complex by the ileal receptors.
- Failure in the reabsorption of vitamin B12 that is secreted in the bile.
Vitamin B12 deficiency during pregnancy may cause neural tube defects, infertility issues, recurring abortions, ataxia, hypotonia and anemia.Serum total homocysteine and methyl malonic acid (MMA) levels have been recommended as sensitive indicators of vitamin B12 status in pernicious anemia patients who generally do not possess any significant metabolic issues.The patients with pernicious anemia have been advised to take 500 – 1,000mcg of vitamin B12 every day as an oral supplement. Otherwise, 100 mcg IM injection once daily for 6-7 days, later administered every other day for 7 doses and followed by every 3-4 days for around 3 weeks and finally,100 mcg IM injection should be taken once every month for a lifetime.
Megaloblastic anemia and Vitamin B12
Megaloblastic anemia, a sign of either vitamin B12 and/or folate deficiency can be hidden by the ingestion of a large amount of folic acid (or folate), but the progressive damage to the nervous system may continue due to the ‘masked’ vitamin B12 deficiency. Therefore,more than 1,000 mcg of folate per day is not advisable without the intake of a B12 supplement at significant doses.Treatment of vitamin B12 deficiency can be achieved using the different routes of administration (oral, IV or intra-muscular [IM]injection).
The most effective dose for the oral supplementation of vitamin B12 ranges between 647-1,032 mcg. IM injection of hydroxycobalamin (100-200 mcg) is used for maintenance therapy whereas the usual dose of 30 mcg can be given for 5-10 days. Some may have access to inhalationalB12, 500 mcg of active cobalamin inhaled by nostril once in a week has been recommended.
The Possible role of Vitamin B12 in cardiovascular disease
Raised levels of plasma homocysteine are often considered a concerning factor incardiovascular disease (CVD), which comprises hypercholesterolemia, hypertension and obesity.Of note, vitamin B12 and folate arethe principal active molecules in homocysteine metabolism, paricularly where it may be the risk factor in the pathogenesis of cardiovascular disease.
Plenty of clinical trials revealed that a combination of folate and vitamin B12 would be considered a therapeutic option to reduce the plasma homocysteine levels that might be a risk factor in CVD. However, the studies did not reveal the role of vitamin B12 in CVD and how it lowers homocysteine levels. Patients with CVD were shown to have a reduction of 32% of homocysteine levelsafter 12 weeks of administration with 250 µg of vitamin B12 and 5 mg of folic acid. The study was comprised of men and women ages 70 to 93 years old. Everyday the participants were administereda combination of vitamins, particularly vitamin B6 (3 mg), vitamin B12 (500 µg) and folic acid (0.8 mg) which remarkably decreased the homocysteine levels.
The studyfocused on whether the low serum levels of vitamin B12 or hyperhomocysteinaemia are precisely associated with CVD events and the research outcome revealed the increase in the CVD recurrent incidences with high plasma levels of homocysteine, not with low serum concentration of vitamin B12.Approximately 20% increased risk of CVD health issues has been noted for each 5 µmol/L when the serum homocysteine levels are above 10 µmol/L.
Reports say that vegetarians tend to have more than 10 µmol/L mean homocysteine plasma levels and high risk of CVD due to their low vitamin B12 levels. The homocysteine hypothesis established from many large scale clinical trials and observational studiesstill has ongoing controversial research questions to be answered in order to fully evaluate the association between vitamin B12 and folate deficiency.
It is well worth taking a minute to note that methylated folate or L-Methylfolate is the most effective form of folate available on the market to reduce homocysteine levels. It’s the most active enzyme form which gets around any potential genetic challenges (for over half the population deals with mutations on the folate metabolism gene, MTHFR, which prevent proper folate absorption – and therefore optimal homocysteine reduction).
Vitamin B12’s function in cognition and nervous system
The pathogenic characteristics of homocysteine in the CVD are very well established through plenty of clinical trials, however, its harmful effects on cognitive impairment, brain function and the nervous system are under investigation. The increased levels of homocysteine significantly reduce the cognitive activities in the normal aging inhabitants. Dementiaor mild cognitive patientsadministered with1 mg folic acid and 1 mg vitamin B12 were reported to have reduced levels of the plasma homocysteine concentration by 30%, however, this combination of B vitamins did not affect the cognitive function.
Conversely, some studies claim that folate could be a very beneficial biomolecule in the management of cognitive impairmentas compared to vitamin B12. It has been documented from research studies that usage of vitamin B12 has not significantly improved the cognitive function, the behavioral and psychological symptoms of depression or dementia. Mixed research outcomes would require copious numbers of long-term studies using biomarkers of vitamin B12 status and interventional studies to elucidate the potential effects on cognition and nervous system.
Vitamin B12 in birth outcomes
Failure of the closing of the neural tube during gestation results in neural tube defects (NTD). Research studies revealed that folate has been reported for its therapeutic effects on spina bifida, anencephaly and encephalocele which are known as NTDas the folate fortification has bettered the birth outcomes.
Again the specific form L-Methylfolate is your champion in regards to having the most positive affect on this population. In addition to the administration of folate, appropriate plasma levels of vitamin B12 are also essential to unveil the beneficial effects on NTD.
The deficiency of vitamin B12 has been shown as a contributing factor for NTD because vitamin B12 is a cofactor for methionine synthase in the folate cycle. The usage of folate for DNA synthesis in the methylation cycle has been processed when the concentrations of vitamin B12 is low, as a result, cell replication is disturbed. Genetic variations that candisruptfolate and vitamin B12 metabolism have been observed in the population who have a risk for NTDs. Low levels of vitamin B12, a mutation in the MTHFR gene, and together with a polymorphism in methionine synthase reductase, has been demonstrated to trigger the risk of NTDs.
Check out Methyl-Life’s™ line of professional supplements if you’re looking for the most active forms of vitamin B12 at therapeutic doses which can provide the beneficial effects mentioned above and treat your deficiency challenges.
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