Low Pyridoxine Does NOT Cause High Prolactin Levels
Low pyridoxine (vitamin B6) deficiency does not cause elevated prolactin levels in humans; in fact, the opposite relationship exists—pyridoxine deficiency is associated with reduced prolactin secretion, not elevation. 1
The Evidence Against Low B6 Causing Hyperprolactinemia
Animal Studies Show the Opposite Effect
- In pyridoxine-deficient adult male rats, plasma prolactin concentrations were significantly reduced compared to control animals receiving adequate pyridoxine supplementation. 1
- When pyridoxine was administered to deficient rats, plasma prolactin levels increased significantly, demonstrating that B6 deficiency suppresses rather than elevates prolactin. 1
- The reduction in prolactin corresponded with decreased hypothalamic serotonin content, suggesting impaired serotonergic regulation of prolactin release in pyridoxine deficiency. 1
Clinical Trials Show No Consistent Effect
The historical literature on pyridoxine treatment for hyperprolactinemia shows conflicting and largely negative results:
One small positive study (1976) reported that three women with galactorrhea-amenorrhea syndrome and elevated prolactin experienced normalization of prolactin and return of menses with high-dose pyridoxine (200-600 mg/day), but this effect disappeared when pyridoxine was discontinued. 2
Multiple subsequent studies failed to replicate these findings:
- Pyridoxine did not suppress elevated prolactin levels in postpartum women or in patients with chlorpromazine-induced hyperprolactinemia and galactorrhea. 3
- Two months of B6 therapy failed to decrease galactorrhea, restore menses, or reduce prolactin levels in nine subjects with galactorrhea-amenorrhea syndromes. 4
- Chronic pyridoxine administration in healthy women showed only slight, statistically insignificant reductions in basal and TRH-stimulated prolactin levels. 5
Actual Causes of Hyperprolactinemia
The established causes of elevated prolactin do not include pyridoxine deficiency. According to the Endocrine Society guidelines, hyperprolactinemia results from: 6
- Prolactinomas (most common pathological cause, with levels typically >4,000 mU/L) 6
- Medications (dopamine antagonists, antipsychotics) 6
- Primary hypothyroidism (reported in 43% of women and 40% of men) 6
- Chronic kidney disease (30-65% of adult patients) 6
- Severe liver disease 6
- Pituitary stalk compression by mass lesions 6
- Stress (can elevate prolactin up to five times the upper limit of normal) 6
Clinical Populations at Risk for B6 Deficiency
While pyridoxine deficiency is a real clinical concern in certain populations, it manifests with different symptoms, not hyperprolactinemia: 7
- Clinical manifestations of B6 deficiency include seborrheic dermatitis with cheilosis and glossitis, microcytic anemia, epileptiform convulsions, confusion, depression, and angular stomatitis. 7
- High-risk populations include alcoholics, renal dialysis patients (especially continuous renal replacement therapy), the elderly, post-operative patients, those with infections or critical illness, pregnant women, and people receiving medications that inhibit vitamin activity (isoniazid, penicillamine, anti-cancer drugs, corticosteroids, anticonvulsants). 7
Clinical Bottom Line
If a patient presents with hyperprolactinemia, do not attribute it to pyridoxine deficiency. Instead, follow the established diagnostic algorithm: 8
- Confirm hyperprolactinemia with repeat measurement 8
- Review medications (particularly dopamine antagonists) 8
- Screen for pregnancy, primary hypothyroidism, liver disease, and renal disease 8
- Assess for macroprolactinemia in mildly elevated cases 8
- Obtain pituitary MRI when prolactin is significantly elevated 8
- Consider dopamine agonist therapy (cabergoline preferred) for confirmed prolactinomas 8