Vitamin B12

Vitamin B12 is a natural supplement belonging to the supplement category of the water-soluble vitamins class.

Vitamin B12 is also known as cobalamin and cyanocobalamin.

Deficiency of vitamin B12 can lead to anaemias including megaloblastic and macrocytic anaemia, a condition in which the healthy red blood cells is reduced.

Intrinsic factor, a protein released by gastric parietal cells, helps in the absorption of vitamin B12 in the small intestine. Transcobalamin-II then distributes to various tissues where it is used in cellular metabolism. Excess vitamin B12 is eliminated from the body in the urine through the kidneys.

The common side effects of Vitamin B12 include fatigue, breathlessness, nausea, headache, pale skin, rash and shortness of breath.

Vitamin B12 is available in various forms, like of tablets, injectable solutions and nasal spray.

Nutritional yeast, fortified foods, cereals, mushrooms, and some algae, are natural plant sources of Vitamin B12. The main sources of Vitamin B12 found in animals are dairy products, meat, poultry, and fish.

Biochemical action of vitamin B12

Vitamin B12, belonging to the supplement class acts as an antioxidant agent. vitamin B12 acts by participating in the methionine-homocysteine pathway.

The biological activity of vitamin B12 is to assist methionine synthase in converting homocysteine to methionine, which facilitates a number of methylation processes and protein synthesis. Additionally, the process of myelin formation it plays a vital role in the formation of red blood cells as well as the preservation of the integrity of nerve cells. The recycling of folate coenzymes, which are necessary for DNA synthesis and cell division, also involves vitamin B12.

• Serves as a cofactor: For the metabolism of carbohydrates, proteins, and fats, cellular growth and development all need vitamin B12. It promotes the activation folacin coenzyme and production of red blood cell.
• Homocysteine reduction: Methionine synthase uses methylfolate to convert homocysteine to methionine, which is generated possibly by methylcobalamin. S-adenosyl-l-methionine (SAMe), which is necessary for methylation processes and protein synthesis, is produced from methionine in a subsequent step. Depression and pernicious anaemia symptoms have been linked to abnormal homocysteine and SAMe levels.
• Antioxidant capacity: Recent investigations have shown that therapeutic doses of vitamin B12 and its cobalamin-based derivatives are strong antioxidants. Vitamin B12 reduces homocysteine levels, helping prevent oxidative damage and promoting cellular health and anti-inflammatory effects.
• Immune system: In order to maintain a balanced and controlled immune function, vitamin B12 acts as an immunomodulator, regulating the immune system's activity and response.

Vitamin B12 is available in the form of tablets, capsules, sublingual, and nasal spray.

• Tablets/ capsules: To be swallowed whole with water/liquid, as applicable.
• Tablet, sublingual: To be placed either on or under the tongue. Allow complete dissolving, then swallow it with saliva, as applicable.
• Nasal Spray: To be sprayed into one nostril, as applicable.

Supplemental Vitamin B12 is utilised for supporting certain physiological metabolic processes.

Vitamin B12 supplement is used in treating vitamin B12 deficiency in individuals with poor dietary intake or malabsorption conditions.

Megaloblastic anemia which is caused by folic acid deficiency is managed by intake of vitamin B12 supplement.

Vitamin B12 supplement helps in the formation of DNA, the genetic material found in all of your cells, as well as maintaining the health of your body's blood and nerve cells.

Vitamin B12 supplement enhances cognitive function and memory, especially in the elderly.

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

Vitamin B12 may be useful as a supplement for the following health benefits:

• Deficiency: treatment and prevention -Vitamin B12 supplementation has traditionally been employed to treat or prevent deficiency in ailments which include pernicious anemia and atrophic gastritis, but the elderly require special attention as they are at a higher risk.
• Pernicious anaemia- A deficiency of intrinsic factors leads to vitamin B12 malabsorption, which causes pernicious anemia. Pallor, glossitis, weakness, and neurological disorders such as paraesthesias, slowed reflexes, and sensory/motor abnormalities constitute the symptoms. Confusion, memory loss, and mood swings may occur in severe situations. Blood transfusions and urgent parenteral vitamin B12 and folic acid therapy are administered intramuscularly as well as blood transfusions.
• Atrophic gastritis- B12 therapy improves the symptoms of vitamin B12 deficiency in elderly patients with atrophic gastritis
• Infants- A severe vitamin B12 deficiency in babies can result in neurological symptoms such as irritability, failure to thrive, lethargy, anorexia, and developmental regression. Supplementation is effective in treating these symptoms.
• Elderly- Elderly people frequently lack vitamin B12, which has been linked to vascular disease, depression, and cognitive decline.In cases of malabsorption, low doses (5.9 mcg/day) can help enhance B12 status. Short-term supplementation for hearing loss, however, hasn't demonstrated any significant advantages
• Hyperhomocysteinaemia- vitamin B12 may not be enough to bring increased homocysteine levels back to normal. As a result, when homocysteine is believed to be a contributing factor to disease, vitamin B12 is frequently advised in addition to folic acid and vitamin B6.
• Cardiovascular protection- Homocysteine levels can be reduced to lower the risk of cardiovascular disease.
• Neural tube defects- Without vitamin B12, folate cannot function effectively. A postpartum study of serum B12 levels has also revealed an increased risk of neural tube abnormalities in women with low B12 status.
• Adjuvant treatment in hepatitis C infection- The administration of vitamin B12 with standard treatment only in antiviral-naïve patients with chronic hepatitis C virus infection has significantly improved viral response compared to standard treatment.

• Orally: All oral solid forms of vitamin B12 are often taken before or after meals, however, it's generally recommended to take atleast 30 minutes on an empty stomach.
• Parenterally: The injectable solution of vitamin B12 is administered through an intramuscular (IM) injection.
• Nasal Spray: When using the nasal spray solution of vitamin B12, one nostril must be closed while the solution is sprayed into the other. During administration, the individual should lean their head slightly forward and breathe slowly through the nostrils.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional.

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablet: 100mcg, 250mcg, 500mcg, 1000mcg
• Tablet, extended release:1000mcg
• Tablet, sublingual: 2500mcg
• Injectable solution: 1000mcg/mL
• Nasal spray: 500mcg/spray. 

Dosage Adjustment in Adult Patients

Dietary supplement: 50 to 6,000 mcg per day.

Pernicious Anemia

Manufacturer recommendation: 100 mcg intramuscularly/ subcutaneously (IM/SC) once daily for 6 to 7 days, then every other day for 7 doses, then every 3 to 4 days for 2-3 weeks, then monthly.

Alternative parenteral dosing: 1000 mcg IM/SC once daily for first 7 days, then weekly for 1 month, then monthly.

Nasal spray: 500 mcg (1 spray in 1 nostril) weekly but if the patient is taking hot meals it is recommended that the spray should be administered 1 hour before or after a meal.

B12 Deficiency

Initial: 30 mcg IM once daily for 5 to 10 days

Maintenance: 100-200 mcg IM monthly

Nasal dose: 500 mcg once weekly.

Vitamin B12 is available in the form of tablets, injectable solutions and nasal spray.

• Limit the consumption of drinks that include caffeine, such as coffee, tea, chocolate, and alcoholic beverages, as this substance could hinder the absorption of Vitamin B12.
• Avoid the consumption of foods that are high in fat or cholesterol, or cobalamin will be less effective.
• Stay within your daily calorie needs.
• Avoid spicy foods.

The dietary restriction should be individualized as per patient requirements.

Recommended Daily Allowance (RDA)

The RDA for adults is 2.4 μg/day.

Upper Tolerable Intake (UTL):

No UTL is set for Vitamin B12 as data concerning adverse effects are not sufficient.

• Hypersensitivity to the product; sensitivity to cobalt.
• Parenteral cyanocobalamin should never be administered intravenously to treat vitamin B12 deficiency caused by malabsorption; rather, it should be injected intramuscularly or deeply subcutaneously.
• Supplementing with folic acid can mask a B12 deficit status.
• Patients with persistent cyanide poisoning who have altered cobalamin metabolism or cobalamin insufficiency shouldn't receive cyanocobalamin treatment.
• Thrombocytosis may occur treatment of severe vitamin B12 megaloblastic anaemia.
• Take attention when administering intranasally to individuals who have nasal pathology or are on concurrent treatment.
• Aluminium may be present in parenteral products; toxic aluminium concentrations may develop with renal impairment, large dosages, or prolonged use.

The treating healthcare professional must closely keep a watch and monitor for signs and symptoms of adverse reactions, such as allergic responses, gastrointestinal disturbances, or neurological abnormalities.

For patients who already have kidney or liver failure, routine testing of vitamin B12 levels and liver function may be recommended. Patients who have underlying illnesses like Leber's disease or megaloblastic anaemia need to be treated with special caution and care. Women who are pregnant or nursing should follow the dose recommendations. When an overdose or unfavourable effects are identified, prompt medical attention must be sought.

It is reportedly safe and well-tolerated to take vitamin B12 oral supplements. However, there have been cases of adverse effects from parenteral cobalamin.

The adverse reactions related to Vitamin B12 can be categorized as-

• Common: Mild diarrhea, itching, and rash
• Less Common: Dizziness, headache, and nausea
• Rare: Anaphylaxis or chest pain.

• Carbamazepine: Monitor for signs and symptoms of B12 insufficiency since long-term carbamazepine treatment has been linked to lower vitamin B12 levels in children. With prolonged therapy, increased consumption can be recommended.
• Colchicine: Colchicine usage may decrease the absorption of vitamin B12 taken orally; monitoring blood B12 levels is advised, especially if there is previous evidence of a shortage.
• Gastric acid inhibitors: For protein-bound vitamin B12 to be released, stomach acid is required. Omeprazole or H2 receptor antagonists may decrease B12 absorption over time, resulting in deficiency. Supplemental vitamin B12 may be needed for long-term treatment.
• Hydrochlorothiazide: Many drugs, including hydrochlorothiazide, have the potential to raise homocysteine levels; as a result, taking vitamin B12 concurrently with folic acid may be an advantageous adjuvant – possible beneficial interaction.
• Oral contraceptives: In a 2003 research, women who used oral contraceptives had lower cobalamin levels, probably as a result of the actions of the B12-binding protein rather than a deficiency. Examine signs and symptoms, and get any necessary assessment.
• Lithium: The therapeutic significance of these findings is not yet evident however lithium therapy may cause a decrease in blood B12 levels. A positive connection is possible
• Metformin: Metformin has been demonstrated to lower levels of vitamin B12 (and folate) and elevated homocysteine in individuals with type 2 diabetes. Supplementation may be beneficial.
• Phenobarbitone and phenytoin: Monitor patients who are taking this combination; according to one clinical research, long-term usage of phenobarbitone and phenytoin together led to significantly higher blood levels of vitamin B12.
• Tetracycline antibiotics: The bioavailability of tetracycline hydrochloride may be greatly decreased by tetracycline antibiotic B complexes including B12 — separate doses by at least 2 hours.
• Sodium valproate: Plasma vitamin B12 concentrations have been shown to increase after sodium valproate administration; one research reported increases of over 50% from baseline.

The common side effects associated with Vitamin B12 include

• Fatigue
• Nausea
• Mild diarrhea
• Headache
• Itching or rash
• Nervousness or restlessness
• Pale skin
• Muscle cramps
• Weight loss
• Numbness
• Poor imbalance
• Dizziness
• Breathlessness
• Swelling of the face, lips, tongue, or throat

These side effects are usually mild and occur only at higher doses of Vitamin B12 supplementation.

• Pregnancy: Vitamin B12 is considered safe in pregnancy. The administration of the approved recommended dose is not expected to result in serious birth abnormalities, miscarriage, or adverse maternal or foetal outcomes. Prophylactic vitamin B12 supplementation, especially in vegetarian mothers, is required.

The recommended daily intake of Vitamin B12 is 1.9 mg/day.

Pregnancy Category: A/C-when exceeding RDA recommendations.

Safe during pregnancy but when taken in high doses use with caution if the benefits outweigh the risks.

There is no sufficient scientific evidence regarding the use and safety of Vitamin B12 for special populations.

• Paediatrics:

Vitamin B12 is vital for neural myelination, brain development, and cognitive function.

Dosage Adjustment for Paediatric Patients

Pernicious Anemia

30 to 50 mcg IM/SC once daily for &ge2 weeks for a total dose of 1,000 mcg to 5,000 mcg administer simultaneously with 1 mg/day of folic acid for 1 month

Maintenance dose: 100 mcg IM/SC monthly

B12 Deficiency

0.2 mcg/kg for 2 days and then by 1,000 mcg/day for 2 to 7 days; follow by 100 mcg/day for 2 to 7 days; then 100 mcg/week for 1 month.

Maintenance dose: 100 mcg IM/SC monthly

• Geriatrics:

Vitamin B12 is an excellent antioxidant- helping maintain the cells' health and function, thus reducing the risk of advancing age-related diseases, such as heart disease and dementia.

There is no sufficient scientific evidence traceable regarding the use and safety of Vitamin B12 for use in special populations

• Lactating mothers:

Vitamin B12 is naturally present in human milk and administration of the approved recommended dose is not expected to cause any harm to a breastfed child.

The recommended daily intake for lactating mothers is 2mg.

There is no sufficient scientific evidence traceable regarding the use and safety of Vitamin B12 for use in special populations.

Dosage Adjustment in Kidney Impairment

Vitamin B12 (cobalamin) dose may need to be modified in the event of kidney disease or malfunction to avoid potential side effects.

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

High cobalamin dosages might worsen liver damage. If you have liver disease, avoid using high doses as metabolism of Vitamin B12 may be altered.

There are no specific dosage adjustments provided.

Overdosage of Vitamin B12 supplements is very rare because large doses are excreted in the urine. On extremely high doses may show symptoms like headache, nausea, dizziness and skin rashes which are self-limiting.

There is no specific treatment that is recommended in the event of an overdose. When an overdose is suspected, cobalamin should be terminated immediately. Supportive treatment should also be given along with addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Biochemistry profile of vitamin B12:

Vitamin B12 is also known as cobalamin, a water soluble vitamin that plays a vital role in various biochemical processes.

Bacteria and archaea are the main producers of vitamin B12, and have a complex biochemistry profile. With the help of intrinsic factor released by gastric parietal cells, it is absorbed in the human body in the small intestine. B12 contributes to the production of methionine and nucleotides and the metabolism of fatty acids as a vital cofactor for enzymes. It is necessary for the formation of red blood cells, DNA synthesis, and neuronal activity. Additionally, B12 is important for the transformation of homocysteine to methionine for the synthesis of DNA and protein methylation, as well as for the conversion of methyl malonyl-CoA to succinyl-CoA, which is a crucial step in the synthesis of fatty acids and the production of energy.

Kinetic Profile:

• Absorption: Cyanocobalamin is rapidly absorbed from injection sites and reaches its peak within an hour of intramuscular injection 6.1% of the bioavailability is estimated.
• Distribution: Distributed primarily to the liver, bone marrow, and other tissue where transcobalamin I and II Absorbed vitamin B12, which is transported via B12 binding proteins
• Metabolism: Cyanocobalamin is transformed into a cofactor for several metabolic pathways in tissues.
• Excretion: The kidney is principally responsible for excreting cynocobaline. The amount of injectable cyanocobalamin found in urine ranges from 50 to 98%. The first eight hours noted the most significant amount of excretion. Daily, the bile secretes 3–8 mcg of cyanocobalamin into the GI tract, most of which is absorbed back.

• Braun L, Cohen M. October 1, 2014.Herbs and Natural Supplements; 4th Edition Vol-2. Australia. Elsevier.
• https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
• https://ods.od.nih.gov/factsheets/VitaminB12-Consumer/
• https://www.ncbi.nlm.nih.gov/books/NBK555964/
• https://www.ncbi.nlm.nih.gov/books/NBK114302/
• https://www.ncbi.nlm.nih.gov/books/NBK554545/