Long-Term Treatment with High-Dose Thiamine in Parkinson Disease: An Open-Label Pilot Study

To investigate the potential clinical, restorative, and neuroprotective effects of long-term treatment with thiamine in Parkinson disease (PD).

Observational open-label pilot study.

Outpatient neurologic rehabilitation clinic.

Starting in June 2012, we have recruited 50 patients with PD (33 men and 17 women; mean age, 70.4 ± 12.9 years; mean disease duration, 7.3 ± 6.7 years). All the patients were assessed at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) and the Fatigue Severity Scale (FSS) and began treatment with 100 mg of thiamine administered intramuscularly twice a week, without any change to personal therapy. All the patients were re-evaluated after 1 month and then every 3 months during treatment.

Thiamine treatment led to significant improvement of motor and nonmotor symptoms: mean UPDRS scores (parts I-IV) improved from 38.55 ± 15.24 to 18.16 ± 15.08 (p = 2.4 × 10(-14), t test for paired data) within 3 months and remained stable over time; motor UPDRS part III score improved from 22.01 ± 8.57 to 9.92 ± 8.66 (p = 3.1 × 10(-22)). Some patients with a milder phenotype had complete clinical recovery. FSS scores, in six patients who had fatigue, improved from 53.00 ± 8.17 to 23.60 ± 7.77 (p < 0.0001, t test for paired data). Follow-up duration ranged from 95 to 831 days (mean, 291.6 ± 207.2 days).

Administration of parenteral high-dose thiamine was effective in reversing PD motor and nonmotor symptoms. The clinical improvement was stable over time in all the patients. From our clinical evidence, we hypothesize that a dysfunction of thiamine-dependent metabolic processes could cause selective neural damage in the centers typically affected by this disease and might be a fundamental molecular event provoking neurodegeneration. Thiamine could have both restorative and neuroprotective action in PD.