Studies on high-dose vitamin B1 in Parkinson’s Disease

The Beneficial Role of Thiamine in Parkinson’s Disease: Preliminary Report - 2012

(1) Khanh vinh quoc Luong, Lan Thi Hoang Nguyen, The Beneficial Role of Thiamine in Parkinson’s Disease: Preliminary Report, J Neurol Res. 2012, 2 (5):211-214

Brief description
This case report describes five male patients with Parkinson’s Disease (PwP), 65-82 years old, who were successfully treated with parenteral High Dose Thiamine - HDT (100-200 mg intramuscularly daily) in the US. All patients showed a remarkable improvement within days of treatment. In three patients who were on treatment with carbidopa / levodopa, the drug was discontinued after 10-14 days of thiamine treatment without any effects on motor signs.

The three cases in whom carbidopa / levodopa was discontinued had the following characteristics:
  • had been diagnosed 3, 7 and 8 years before, respectively - so the PD duration was not very short, at least in 2 of them
  • had many symptoms
  • were on carbidopa / levodopa at relatively low doses (25/100 x 2/day)
  • received 200 mg/day of thiamine i.m. – so, rather high doses of B1

Brief commentary
This case report describes the potential beneficial effects of high dose thiamine administered via the intramuscular route in PwP. Patients, all males, were treated in the US. All of them showed remarkable symptom improvement within days. Although carbidopa / levodopa was discontinued in 3 of them without immediate worsening of motor symptoms, it is not clear for how long they were followed up and thus whether they continued parenteral thiamine. It is also not reported whether they continued to stay with no carbidopa / levodopa or whether symptoms reappeared and they had to restart carbidopa / levodopa to control them.

High-dose thiamine as initial treatment for Parkinson's disease - 2013

(2) A. Costantini, MI Pala, L. Compagnoni, M. Colangeli, High-dose thiamine as initial treatment for Parkinson's disease, BMJ Case Rep 2013 Aug 28, ii: bcr2013009289

Brief description
In this case report, Dr Costantini et al. describe three patients treated with high dose thiamine parenterally (100 mg twice a week). After 15 days, treatment resulted in a significant improvement in total UPDRS (Unified Parkinson's Disease Rating Scale parts I-IV), with a score reduction ranging from 31% to 71.4%. As a standard procedure, small doses of all other group B vitamins were administered to the patients of this study two times a week, when patients received high dose thiamine.

Dr Costantini hypothesizes that a thiamine metabolism dysfunction (intracellular thiamine transport) would cause a focal severe thiamine deficiency with neuronal damage in the centres most affected by Parkinson’s disease, determining Parkinson’s Disease symptoms. Given the lack of blood thiamine deficiency and given the good response to treatment, he argues that this dysfunction could be reversed by high thiamine concentrations achieved by administration of high doses of thiamine, which would result in an increase in thiamine diffusion transport.

Brief commentary
Unlike the study carried out in the US, the patients reported in this case report were treated in Italy. The findings were remarkable also in this case and, despite the use of lower doses of intramuscular thiamine than the US patients, symptom improvement was apparent quickly within the first 2 weeks, similarly to the US report. It is interesting also to note that the researchers added small amounts of B-complex to the high dose thiamine protocol. B vitamins interact with each other and the high doses of vitamin B1 used may require supplementation with these vitamins.

Long-Term Treatment with High-Dose Thiamine in Parkinson Disease: An Open-Label Pilot Study - 2015

(3) A. Costantini, MI Pala, E. Grossi, S. Mondonico, L. Ercoli Cardelli, C. Jenner, S. Proietti, M. Colangeli, Roberto Fancellu, Long-Term Treatment with High-Dose Thiamine in Parkinson Disease: An Open-Label Pilot Study, J Altern Complement Med. 2015 Dec;21(12):740-7

Brief description
This was an observational, open-label pilot study conducted on 50 outpatients with Parkinson’s disease. Patients were followed up for 95 to 831 days (i.e. from about 3 months up to 2.3 years) and re-evaluated after 1 month and then every 3 months during treatment. The researchers noted a significant improvement of motor and non-motor symptoms. Mean UPDRS I-IV scores (Unified Parkinson's Disease Rating Scale) improved from 38.5 to 18.2 within 3 months and remained stable over time; UPDRS III score (motor signs) improved from 22.0 to 9.9. An increase in the UPDRS score represents an increase in severity, while a decrease represents an improvement. Some patients with mild symptoms showed full clinical recovery. The authors concluded that “thiamine could have both restorative and neuroprotective action in Parkinson’s Disease”.

Brief commentary
This was an open-label study. Open-label studies are studies in which both participants and researchers know which treatment each participant in the study is receiving. The study was therefore potentially subject to what is called the “placebo effect”, an effect linked to participants’ high expectations that what is being received will produce beneficial effects. However, despite this limitation, it was the first study on HDT in Parkinson’s disease with a relatively large number of participants (50), in which some of them were followed up for a long period, up to more than 2 years. Improvement was noted not only in motor signs but also in non-motor signs. One of the most significant findings is the fact that symptom improvement assessed through the UPDRS remained stable over time during the study. This result is difficult to explain with the placebo effect, which is unlikely to persist for so long.

Effects of Overdose of High-Dose Thiamine Treatment, Gerontology & Geriatrics Studies - 2018

(4) A. Costantini and R. Fancellu, Effects of Overdose of High-Dose Thiamine Treatment, Gerontology & Geriatrics Studies, December 06, 2018

Brief description and commentary
In this paper, Dr Costantini and Dr Fancellu describe their experience with high dose thiamine in patients with Parkinson’s Disease. They make some important considerations;
  • High dose thiamine was administered in addition to, and not in replacement of, classic therapy, which was therefore not discontinued.
  • Higher doses of thiamine were given to patients with:
a. longer disease duration
b. higher symptom severity
c. high body weight (> 90 Kg).
  • High dose thiamine was given (orally) also to patients on anticoagulants.
  • 100 mg of thiamine given intramuscularly once a week were estimated to be equivalent to an oral dose 140 times as high (e.g. corresponding to 14 grams/week, that is 2 grams/day).
  • High dose thiamine was well tolerated.

They also noted that at doses too high for an individual patient, the initial improvement in the first two weeks would be followed by symptom worsening, with a general feeling of discomfort, unrest and a moderate migraine. Stopping treatment for a week in these cases was accompanied by the disappearance of those symptoms. This pattern was observed more frequently in patients:
a) newly diagnosed
b) with mild symptoms
c) with small body mass

Treatment would then be resumed at half the original dose and then adjusted to obtain symptom improvement without side effects.

The Authors also noted that patients of Anglo-Saxon and African origin required smaller doses than the Italian ones and could show signs of an excessive thiamine dose as soon as even the first day of treatment.

They concluded that the correct individual dose was the dose leading to symptom improvement, including the sense of balance with almost normalization of the pull-test, and no side effects.

Text author: Sergio Pièche
Page updated - 24/04/23