STEPTRACKERBIOCHEMISTRY + HEMATOLOGY | NUTRITION | HIGH-YIELD REVIEW

B Vitamins II — B7, B9, B12 & Vitamin C

Biotin carboxylates, folate and B12 move one-carbon units for DNA, and vitamin C keeps collagen and iron working.

FOCUS ON
Folate and B12 deficiency both give megaloblastic anemia and ↑ homocysteine; only B12 raises methylmalonic acid and damages nerves (subacute combined degeneration). Folate stores last months, B12 stores years. Biotin = carboxylases (pyruvate, acetyl-CoA, propionyl-CoA carboxylase); raw egg whites (avidin). Vitamin C = collagen hydroxylation, iron absorption, dopamine β-hydroxylase → scurvy.
VITAMIN
FUNCTION
DEFICIENCY
CAUSE · CLUE
B7 — biotin
Cofactor for carboxylases: pyruvate → oxaloacetate, acetyl-CoA → malonyl-CoA, propionyl-CoA → methylmalonyl-CoA
Dermatitis, alopecia, enteritis, lactic acidosis
Raw egg whites (avidin binds biotin), long-term antibiotics
B9 — folate
THF carries one-carbon units for purine and thymidine synthesis; absorbed in jejunum
Megaloblastic anemia, hypersegmented neutrophils, glossitis, no neuro signs; ↑ homocysteine, normal MMA
Alcohol, pregnancy, poor diet, MTX, trimethoprim, phenytoin, sulfa · neural tube defects if low early in pregnancy
B12 — cobalamin
Methionine synthase (homocysteine → methionine, regenerates THF) · methylmalonyl-CoA mutase (MMA → succinyl-CoA)
Megaloblastic anemia + neuro: subacute combined degeneration (dorsal columns, lateral CST, spinocerebellar), peripheral neuropathy, dementia; ↑ homocysteine, ↑ MMA
Pernicious anemia (anti-IF, anti-parietal cell), gastrectomy, ileal resection/Crohn, vegan diet, D latum, metformin, PPIs
B12 absorption
Freed by acid/pepsin → R-binder → pancreatic proteases release → intrinsic factor → terminal ileum
Any step can fail
Pancreatic insufficiency also ↓ B12
Folate trap
Without B12, folate stays stuck as N⁵-methyl-THF
Functional folate deficiency
Folate fixes the anemia but not the nerves — never give folate alone if B12 low
Vitamin C — ascorbic acid
Prolyl/lysyl hydroxylation (collagen), keeps iron Fe²⁺ (↑ absorption), dopamine → norepinephrine (dopamine β-hydroxylase)
Scurvy: swollen bleeding gums, perifollicular hemorrhages, corkscrew hairs, bruising, poor healing, anemia, hemarthrosis
Tea-and-toast elderly, restrictive diets · excess → oxalate stones, ↑ iron absorption (hemochromatosis)
Methemoglobinemia treatment
Vitamin C reduces Fe³⁺ → Fe²⁺
—
Methylene blue first-line; vitamin C as adjunct
Homocysteine
Needs B12 + folate (→ methionine) or B6 (→ cystathionine)
↑ Homocysteine → thrombosis, atherosclerosis
Also ↑ in homocystinuria (9.04)

Mechanism — the two B12 reactions

Homocysteine + N⁵-methyl-THF
→
Methionine synthase (B12)
→
Methionine + THFDNA synthesis continues
Methylmalonyl-CoA
→
Mutase (B12)
→
Succinyl-CoAMMA buildup damages myelin if blocked

Folate vs B12 deficiency

FEATURE
FOLATE ↓
B12 ↓
Anemia
Megaloblastic
Megaloblastic
Homocysteine
↑
↑
Methylmalonic acid
Normal
↑
Neuro signs
No
Yes (SCD)
Stores
~3–4 months
~3–5 years

How it's tested

COMMON CONFUSIONBoth deficiencies raise homocysteine; methylmalonic acid separates them (↑ only with B12).
THE TRAPGiving folate to a B12-deficient patient corrects the blood count while the spinal cord keeps degenerating.
YOUR APPROACHMegaloblastic anemia → MMA → neuro signs → cause (diet, drugs, absorption, autoimmune) → replacement route.

If you see… think…

Bodybuilder eating raw eggs, dermatitis, alopecia → biotin deficiency (avidin)
Megaloblastic anemia, normal MMA, alcoholic → folate deficiency
Megaloblastic anemia + ↓ vibration, ↑ MMA → B12 deficiency
Anti-intrinsic factor antibodies → pernicious anemia
B12 deficiency after terminal ileum resection → no IF–B12 absorption
Long-term metformin + neuropathy → B12 deficiency
Neural tube defect prevention → folate before conception
Bleeding gums, corkscrew hairs, perifollicular hemorrhage → scurvy (vitamin C)
Vitamin increasing nonheme iron absorption → vitamin C
Enzymes needing biotin → carboxylases