Reference Country Duration Funding	Design	Subject characteristics at baseline	Intervention	Outcome ascertainment	Results
Berger et al. (1992) USA Subject 1: 7 months Subject 2: 4.5 months Subject 3: 14 months (QST results became abnormal) Subject 4: 3.5 months Subject 5: 1.5 months Note: Pyridoxine discontinued at first evidence of sensory disturbance NR	CT Inclusion/exclusion criteria: NR (cases neurologically normal, except one with poliomyelitis as a child, but not described as in‐ or exclusion criteria) N = 5	Sex (% women): 20 Age (range): 29–55 Serum pyridoxal phosphate (PLP), nmol/L (after 1 month of intervention): Subject 1: 920 Subject 2: 280 Subject 3: NR Subject 4: 690 Subject 5: NR	Vitamin B6 (pyridoxine) dose (mg/day) Subject 1: 1,000 Subject 2: 1,000 Subject 3: 1,000 Subject 4: 3,000 Subject 5: 3,000 Vitamin B6 (mg/kg bw): Subject 1: 12 Subject 2: 19.6 Subject 3: 12 Subject 4: 42.8 Subject 5: 56.9 Background nutrient intake: NR Compliance: NR	Time to onset of clinical symptoms (reflected in duration of exposure) Quantitative sensory threshold (QST) index Method: Clinical neurologic examinations including testing of deep tendon reflexes appreciation to pin, cold, and vibration, motor strength, and gait Physiologic evaluations including 1) Quantitative measurement of the sural sensory potential amplitude and conduction velocity 2) Quantitative vibration thresholds 3) Quantitative thermal thresholds	Symptoms progressed with increasing PLP concentration and after PLP returned to normal Serum PLP (nM) *Subjects 3 + 5: NR Subject 1 Month 1: 920 Month 4: 690 Month 7: 680 Month 8: 10 Subject 2 Month 1: 280 Month 5: 280 Month 5.5: 50 Month 6: 20 Subject 3 did not experience symptoms Subject 4: Month 1: 690 Month 3: 750 Month 5: 0 Thermal and vibrational QST post PLP Subject: 1: returned to normal after 1 month Subject 2: returned to normal over 1 month+ vibrational QST remained elevated Subject 4: continued to worsen over 2.5 months Subject 5: continued to worsen over 1 month Time until serum PLP levels returned to normal after discontinuation (week): Subject 1: 4 Subject 2: 2 Subject 4: 6

bw: body weight; CT: clinical trial; d: day; NR: not reported; PLP: pyroxidal phosphate; QST: quantitative sensory threshold; USA: United States of America; wk: week.