key elements
The B1 protocol developed by Costantini mainly includes three key supplements.
The approach is a progressive incremental approach. It starts with an initial, relatively low oral dose of B1 which is then increased after 4 weeks, if no “overdose” signs or no beneficial effects are noticed earlier.
a) If “Overdose” symptoms occur: after an initial improvement, symptoms may get worse, as described above. This would suggest “overdose”, namely a dose which is too high for that specific individual. According to Costantini’s protocol, B1 would then be stopped for a week or so and then started again at a lower dose, usually half of it (Costantini, 2018). If symptoms improve during the break, then that would confirm that the worsening was due to an excessive dose of B1, “excessive” for that particular PwP. If symptoms do not improve, then worsening of symptoms was more likely related to PD progression or other factors (e.g. stress, infection, etc.) rather than the B1 dose per se, and B1 can be resumed at the same dose in these cases.
b) If no beneficial effects occur: it is possible that the starting dose causes no improvement within the first period of 4 weeks. The dose is then increased – usually doubled – and tested for a period of similar duration. If no overdose symptoms or no improvement occur after that, the dose is increased again for other 4 weeks; and so on until the right dose is found. Oral doses of B1 as low as 25 mg and as high as 4,000 mg have been used by PwP to observe an improvement.
It may take just a few weeks or as long as a few months to find the right dose. With the right dose, symptoms start getting better, often within two to three weeks, but such initial improvement may be very subtle and not perceived as such by the PwP. It’s often people around the PwP who notice the change, whether they are other members of the family, their caregivers, friends, therapists, physician, etc.. After 4 weeks at the right dose, symptom improvement usually becomes more evident. This is why the protocol calls for sticking to the same B1 dosage for 4 weeks before increasing it, if no improvement occurs by then.
- B1 (thiamine)
The approach is a progressive incremental approach. It starts with an initial, relatively low oral dose of B1 which is then increased after 4 weeks, if no “overdose” signs or no beneficial effects are noticed earlier.
a) If “Overdose” symptoms occur: after an initial improvement, symptoms may get worse, as described above. This would suggest “overdose”, namely a dose which is too high for that specific individual. According to Costantini’s protocol, B1 would then be stopped for a week or so and then started again at a lower dose, usually half of it (Costantini, 2018). If symptoms improve during the break, then that would confirm that the worsening was due to an excessive dose of B1, “excessive” for that particular PwP. If symptoms do not improve, then worsening of symptoms was more likely related to PD progression or other factors (e.g. stress, infection, etc.) rather than the B1 dose per se, and B1 can be resumed at the same dose in these cases.
b) If no beneficial effects occur: it is possible that the starting dose causes no improvement within the first period of 4 weeks. The dose is then increased – usually doubled – and tested for a period of similar duration. If no overdose symptoms or no improvement occur after that, the dose is increased again for other 4 weeks; and so on until the right dose is found. Oral doses of B1 as low as 25 mg and as high as 4,000 mg have been used by PwP to observe an improvement.
It may take just a few weeks or as long as a few months to find the right dose. With the right dose, symptoms start getting better, often within two to three weeks, but such initial improvement may be very subtle and not perceived as such by the PwP. It’s often people around the PwP who notice the change, whether they are other members of the family, their caregivers, friends, therapists, physician, etc.. After 4 weeks at the right dose, symptom improvement usually becomes more evident. This is why the protocol calls for sticking to the same B1 dosage for 4 weeks before increasing it, if no improvement occurs by then.
- Magnesium
Thiamine requires magnesium to be activated in the cell; thiamine-dependent metabolic processes also need magnesium (Marrs, 2021; Overton, 2022). Furthermore, PwP often have magnesium deficiency (Oyanagi, 2011). In the presence of magnesium deficiency, there may be a failure to respond to thiamine supplementation. So, magnesium is included in the B1 protocol [Costantini, HDT website].
- B-Complex
B1 at high doses may increase the need for other vitamins and minerals, which share common pathways and interact with each other. Adequate levels of all vitamins of the group-B vitamins are essential for optimal neurological functioning (Kennedy, 2016). Also, in PD there may be a deficiency of some vitamins and minerals. A B-complex with low B vitamins content is the third element of the B1 protocol (Costantini, HDT website).
Selected references
Costantini and R. Fancellu, Effects of Overdose of High-Dose Thiamine Treatment, Gerontology & Geriatrics Studies, December 06, 2018
Marrs C, Lonsdale D., Hiding in Plain Sight: Modern Thiamine Deficiency. Cells. 2021 Sep 29;10(10):2595.
Overton E. , Why Thiamine Supplementation Requires Magnesium, July 7, 2022, accessed 03.01.2022
Oyanagi K, Hashimoto T. Magnesium in Parkinson’s disease: an update in clinical and basic aspects. In: Vink R, Nechifor M, editors. Magnesium in the Central Nervous System [Internet]. Adelaide (AU): University of Adelaide Press; 2011.
Dr Costantini’s website on High-dose Thiamine (HDT) Therapy for Parkinson’s Disease, Accessed 28.02.2023
D. O. Kennedy, B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review, Nutrients 2016, 8, 68
Text author: Sergio Pièche
Page updated - 24/04/23
Page updated - 24/04/23