Does Pyridoxal 5'-phosphate (P5P) lower prolactin levels?

Pyridoxal 5'-Phosphate (P5P) for Lowering Prolactin Levels

Yes, Pyridoxal 5'-phosphate (P5P) can effectively lower elevated prolactin levels, with high-dose vitamin B6 supplementation showing a 68.1% reduction in serum prolactin in clinical studies. 1

Mechanism of Action

P5P, the active form of vitamin B6, works to lower prolactin through several mechanisms:

• Directly inhibits pituitary cell proliferation and hormone secretion
• Reduces prolactin secretion by up to 65% in pituitary cells 2
• Induces cell-cycle arrest and apoptosis in prolactin-secreting cells
• Decreases the content of the antiapoptosis gene Bcl-2 2

Evidence for Efficacy

The strongest evidence comes from a 2021 randomized double-blind controlled study that demonstrated:

• 68.1% reduction in serum prolactin levels (from 95.52 to 30.43 μg/L) after 16 weeks of high-dose vitamin B6 (300 mg twice daily)
• Superior efficacy compared to aripiprazole, which only reduced prolactin by 37.4% 1
• Better alleviation of psychotic symptoms and cognitive impairment
• Lower adverse effect scores 1

Dosing Considerations

For prolactin-lowering effects:

• Therapeutic dose range: 300 mg twice daily (as used in clinical trials) 1
• Standard daily requirements: 1.3-1.7 mg/day for adults 3, 4
• Upper limit (UL): 100 mg/day for adults 19+ years 3, 4

Safety Profile

• High-dose P5P supplementation appears relatively safe in controlled settings 1
• However, caution is warranted as:
  • Excessive vitamin B6 supplementation (>500 mg/day) can cause sensory neuropathy 4
  • The tolerable upper limit is 100 mg/day for adults 3, 4
  • Pharmacological doses used for prolactin reduction exceed this limit

Alternative Treatments for Hyperprolactinemia

For comparison, the standard medical treatment for hyperprolactinemia is dopamine agonists:

• Cabergoline is the dopamine agonist of choice for treating prolactinomas and hyperprolactinemia 3
• Dopamine agonists normalize prolactin in 60-70% of patients 3
• Cabergoline has superior effectiveness and lower adverse effect profile compared to other dopamine agonists 3

Clinical Application

When considering P5P for prolactin reduction:

1. Confirm hyperprolactinemia with laboratory testing
2. Rule out other causes of elevated prolactin
3. Consider standard treatments first (dopamine agonists like cabergoline) 3
4. Monitor for side effects if using high-dose P5P therapy
5. Regularly check prolactin levels to assess response

Potential Pitfalls and Caveats

• P5P supplementation at high doses exceeds recommended upper limits
• Clinical trials showing efficacy used controlled settings with medical supervision
• Bromocriptine has been suggested as adjunctive treatment for peripartum cardiomyopathy to decrease prolactin based on its proposed mechanistic role, but its efficacy has not been established 3
• Nutritionally relevant doses of vitamin B6 (0.5-4.0 mg/day) elevated plasma pyridoxal phosphate without reducing plasma prolactin in lactating women 5

While P5P shows promise for lowering prolactin levels, it should be considered as an adjunctive therapy rather than first-line treatment, with careful monitoring for potential adverse effects when using doses that exceed recommended upper limits.