Vitamin B6 (Pyridoxine / PLP)

Makes mood chemicals

All forms of B6 are converted to pyridoxal 5′-phosphate (PLP). PLP binds amino acids through their nitrogen group and holds them in place so that one specific bond can be broken. That makes it the most versatile coenzyme in the body: PLP enzymes handle about 4% of all catalogued enzyme reactions.¹

One of those reactions removes the acid group (CO₂) from an amino acid, and that turns several amino acids into neurotransmitters:

• Glutamate → GABA (glutamate decarboxylase): this turns the brain's main "excite" signal into its main "calm" signal.
• 5-HTP → serotonin and L-DOPA → dopamine: both use the same PLP enzyme, aromatic L-amino acid decarboxylase. Dopamine is then made into noradrenaline.
• Histidine → histamine, and the serine–glycine conversion that supplies glycine, also a calming neurotransmitter.

The proof in people. In the early 1950s, a batch of infant formula was heat-treated in a way that destroyed its B6. Babies fed it developed seizures, which stopped as soon as they were given B6. The explanation is GABA: without PLP, glutamate decarboxylase can't make enough GABA, and the brain has no brake. The same mechanism explains seizures in pyridoxine-dependent epilepsy, a genetic condition, and in overdoses of isoniazid, a TB drug that inactivates B6. All three are treated with B6.² Milder deficiency shows up as irritability, depression and confusion.

Builds red blood cells

Making heme, the iron-holding ring in hemoglobin, starts with one reaction. ALA synthase joins glycine and succinyl-CoA to make δ-aminolevulinic acid (ALA). ALA synthase needs PLP. In red-cell precursors it's the rate-limiting step, so B6 controls how fast developing red cells can make heme.³

When that step fails, iron is delivered to the developing red cell but can't be put into heme. It piles up in the cell's mitochondria, which form a ring of iron granules around the nucleus that is visible under the microscope (a "ringed sideroblast"). The red cells that come out are small and pale (microcytic), much like in iron deficiency, but the body is actually overloaded with iron. The inherited form, X-linked sideroblastic anaemia, is caused by mutations in ALAS2, and many patients respond partly or fully to high-dose B6, which helps the faulty enzyme bind its cofactor.³ Acquired cases come from heavy drinking, isoniazid and lead poisoning. That's why a small-cell anaemia with normal or high ferritin should prompt a check of B6.

Keeps homocysteine down

Homocysteine is produced every time the body uses a methyl group from methionine (see Methionine). It has two exits. Folate and B12 can recycle it back to methionine. Or B6 can send it down the transsulfuration pathway, where two PLP enzymes (cystathionine β-synthase, then cystathionine γ-lyase) turn it into cysteine, the limiting building block of glutathione. The B6 route matters most after a protein-heavy meal, when there's more homocysteine than recycling can handle.

What the trials found. High homocysteine is consistently linked to heart disease and stroke, and B vitamins reliably lower it. But lowering it hasn't prevented heart attacks. In NORVIT (3,749 heart attack survivors), folic acid with B12 cut homocysteine by 27%. Neither that combination nor 40 mg of B6 reduced repeat events, and the combination of all three hinted at harm.⁴ HOPE-2 (5,522 people with vascular disease) found no reduction in heart attacks or cardiovascular death from folic acid plus B6 and B12, although strokes fell by about 25%.⁵ The honest reading is that homocysteine marks a problem in methylation and sulfur metabolism, and for heart attacks, lowering it with high-dose vitamins doesn't fix the underlying cause. Stroke prevention is the exception worth noting (see Folate).

Uses protein for energy

Before the carbon in an amino acid can be burned or turned into glucose, its nitrogen has to be removed. Transaminases do this. They are PLP enzymes that move the amino group onto α-ketoglutarate, which becomes glutamate, and leave behind a keto acid that can enter the TCA cycle. Alanine becomes pyruvate, aspartate becomes oxaloacetate, and so on. The two transaminases measured in liver tests, ALT and AST, are both PLP enzymes.¹

Glutamate then hands the nitrogen on to the urea cycle for safe disposal. B6 is what lets the body use protein as fuel and get rid of the nitrogen without ammonia building up. That's why B6 requirements rise with protein intake. PLP is also bound to glycogen phosphorylase in muscle. That's where most of the body's B6 is stored, and the enzyme frees glucose from glycogen during exercise.

Intake & safety

The RDA is 1.3 mg/day for adults, rising to 1.5–1.7 mg after age 50. Turning B6 into active PLP needs riboflavin (B2), so poor B2 status can cause a functional B6 shortfall. Inflammation lowers plasma PLP because tissues take more up, so a low blood level in someone who is sick doesn't always mean a dietary shortage.⁶

Top foods

• Tuna (yellowfin): about 0.9 mg in 3 oz
• Salmon: about 0.6 mg in 3 oz
• Chicken breast: about 0.5 mg in 3 oz
• Baked potato with skin: about 0.6 mg (medium)
• Banana: about 0.4 mg (medium)

Deficiency effects

Deficiency on its own is uncommon. It's usually seen with heavy drinking, kidney failure, autoimmune disease or drugs that interfere with B6 (isoniazid, levodopa, some anti-seizure drugs). Signs are irritability, depression and confusion; cracks at the mouth corners and a sore tongue (like riboflavin deficiency); small-cell anaemia; a weakened immune response; and, especially in infants, seizures.²