Vitamin B12

Overview

• Vitamin B12 (cobalamin) is a water-soluble vitamin containing cobalt, essential for human metabolism.
• It acts as a co-enzyme in two key biochemical pathways:
  • Methionine synthesis from homocysteine.
  • Conversion of methylmalonyl-CoA to succinyl-CoA.
• These pathways are crucial for DNA synthesis, red blood cell formation, and neurological function.

Benefits

• Hematologic health: Supports erythropoiesis; deficiency causes megaloblastic anemia (Miller, 2023).
• Neurological & cognitive function: A co-factor for methionine synthase, supporting myelin synthesis; low levels linked to cognitive decline and peripheral neuropathy (Morris et al., 2022).
• Energy metabolism: Facilitates methylmalonyl-CoA conversion, supporting fatty acid catabolism and mitochondrial ATP production.
• Cardiovascular support: Lower homocysteine levels after supplementation reduce atherosclerotic risk in some meta-analyses (Bazzano, 2021).
• Pregnancy & fetal development: Required for neural tube closure; maternal deficiency increases neural tube defects and low birth weight risk (CDC, 2023).

How It Works

• Vitamin B12 functions as a co-enzyme for:
  • Methionine synthase: Transfers a methyl group from 5-methyltetrahydrofolate to homocysteine, regenerating tetrahydrofolate for nucleotide synthesis and producing methionine for S-adenosyl-methionine (SAM), the universal methyl donor.
  • Methylmalonyl-CoA mutase: Uses adenosylcobalamin to rearrange methylmalonyl-CoA to succinyl-CoA, feeding the TCA cycle.
• Both reactions require a central cobalt ion within a corrin ring, cycling between Co¹⁺, Co²⁺, and Co³⁺ oxidation states to accept and donate methyl groups.
• Resulting methylation reactions are essential for DNA replication, myelin formation, and energy production.

Dosage

• Recommended Dietary Allowance (RDA): 2.4 µg/day for adults (higher during pregnancy: 2.6 µg).
• Supplementation for deficiency: 500–1000 µg oral cyanocobalamin or methylcobalamin daily for 2–4 weeks, then 100–500 µg maintenance.
• Clinical high-dose protocols: 1–5 mg daily for pernicious anemia or malabsorption; up to 10 mg weekly injectable for severe deficiency.
• Timing: Oral doses can be taken with or without food; sublingual or intranasal forms bypass gastric acidity.
• Special cases: Vegans/vegetarians often require 25–100 µg/day supplemental; patients on metformin or proton-pump inhibitors may need 500–1000 µg due to reduced absorption.

Safety & Side Effects

• Vitamin B12 has a wide safety margin; excess is excreted in urine.
• Adverse events are rare and may include:
  • Mild gastrointestinal upset.
  • Skin rash.
  • Transient itching (high-dose oral or injectable forms).
• No known toxicity at doses up to 2 g/day.
• Contraindications are minimal, but caution is advised in patients with Leber’s hereditary optic neuropathy (B12 may exacerbate retinal degeneration).
• Drug interactions: Metformin, proton-pump inhibitors, and H₂-blockers reduce absorption; high-dose B12 may interfere with some chemotherapy agents (e.g., methotrexate) by influencing folate metabolism.
• Pregnant and lactating women can safely use standard supplemental doses.

Chemistry

• Vitamin B12 is a complex organometallic compound called cobalamin.
• Molecular formula: C₆₃H₈₈CoN₁₄O₁₄P.
• Contains a central Co³⁺ ion coordinated within a corrin macrocycle (a contracted porphyrin).
• The IUPAC name is extremely long; "cobalamin" is used commonly.
• Key features:
  • Central cobalt atom.
  • Corrin ring.
  • Nucleotide (5′-deoxyadenosyl, cyanide, methyl, or hydroxyl ligand).
  • Dimethylbenzimidazole “lower ligand”.
• Highly polar, water-soluble, stable under acidic conditions, but degrades in light and alkaline pH.

Sources & Quality

• Natural Vitamin B12 is produced exclusively by microorganisms: Propionibacterium, Lactobacillus, and certain Clostridia species.
• Commercially, it's harvested from bacterial fermentation (Pseudomonas denitrificans or Propionibacterium freudenreichii) and purified.
• Synthetic routes (e.g., cyanocobalamin) involve chemical conversion of the natural corrin core, yielding a stable, inexpensive form.
• Methylcobalamin and adenosylcobalamin are produced by microbial biosynthesis and conversion.
• Quality considerations include:
  • Cobalamin form (cyanocobalamin vs. methyl-/adenosyl-cobalamin).
  • Absence of heavy-metal contaminants.
  • Compliance with pharmacopeial standards (USP, EP).
• "Cobalamin-free" (for vegans) is derived from non-animal microbial cultures.