THE CHALLENGE: SEARCHING FOR THE RIGHT DOSE
A major aspect of the protocol is the fact that the dosage of thiamine needs to be individualised, tailored to the single PwP. There is no one-size-fits-all. Costantini defined the right dose as the dose that leads to improvement without causing worsening of the patient’s symptoms [Costantini, 2018].
The process to determine the effective dose of B1 represents a substantial challenge, as to date there is no standard reference guide which has been tested and validated, on which an estimation of the start dose can be based.
Laboratory tests, such as those checking for thiamine blood levels, play no role in B1 therapy. They do not necessarily reflect “thiamine metabolic function” (Whitfield, 2018) or tissue concentrations. More importantly, thiamine in PD is not used to correct a vitamin deficiency, but is rather given at high, pharmacological doses to overcome a situation in which thiamine metabolic processes are possibly no longer working properly. It has been hypothesised that this could be linked to a series of events which occur in PD (e.g. oxidative stress, neuroinflammation, mitochondrial dysfunction, etc.), which may eventually interfere with the ability of the neuronal cell to produce energy. The section on The Scientific Evidence presents more information on this hypothesis.
Some factors influencing the dose in B1 therapy identified by Dr Costantini in his clinical experience include age, gender, weight, and duration and severity of the disease (Costantini, 2018). More systematic research is needed to confirm this and identify other factors, to standardize the approach and confirm its validity.
It is commonly believed that any excess amount of B1 taken orally - such as the one taken with high-dose B1 therapy - would be eliminated through the urine, B1 being a water-soluble vitamin (Laird, 2014). As such, high doses of thiamine should not lead to any “toxic” or unwanted effect. In short, many believe that an “overdose” of B1 can not occur.
However, in clinical practice, a condition characterized by symptom worsening has been described following high doses of thiamine (“overdose”).
Lonsdale talks about the possibility of patient’s symptoms getting initially worse, unexpectedly, when they are given thiamine i.v. for B1 deficiency. He defines this as a “paradoxical” response, as the patient who is deficient in B1 would paradoxically get worse when receiving it, rather than better. However, this phenomenon would be temporary and eventually “herald a good outcome” (Lonsdale, 2015).
Costantini, using the B1 protocol in PwP, reports that a dose which is too high for a specific individual with PD would cause a worsening of symptoms, after an initial improvement of variable duration - from the same day of administration to usually two weeks. He therefore refers to it as an “overdose”. Stopping B1 for a few days would be accompanied by an improvement of those symptoms without any consequences for the PwP (Costantini, 2018).
As described by Bryan, from anectodal reports (Bryan, 2023, unpublished report), “overdose” symptoms following a dose of B1, are symptoms which:
It is important to emphasise that a dose which may be too high for one PwP (“overdose”), may be right or too low for another one.
The body can store a small amount of B1 - between 30 and 50 mg. If the diet is deficient in thiamine, these limited stores may be depleted within 2-3 week (WHO, 1999; Fattal-Valevski, 2011; Marrs 2021).
So, the approach to one’s searching for the right dose of B1 is at present a trial and error approach. A dose which is too high for a PwP (“overdose”) would cause worsening of symptoms, while a dose which is too low (“underdose”) would produce no effects. To complicate things, the natural progression of the disease may also be responsible for symptoms getting worse. The challenge then consists in the ability to identify the dose which, in that individual person with PD, determines an improvement without causing any worsening of symptoms.
This approach, which requires guidance and support, may otherwise cause some degree of frustration in some PwP, who are very eager to start treatment and may erroneously be lead to believe that a “higher” dose is more “powerful” and better.
Costantini also observed in his clinical practice that, unlike the Italian patients, North-American and African PwP tended to require much lower dosages of B1 and could more easily develop “overdose” symptoms, as quickly as even on the first day of B1 therapy [Costantini, 2018].
Selected references
Costantini and R. Fancellu, Effects of Overdose of High-Dose Thiamine Treatment, Gerontology & Geriatrics Studies, December 06, 2018
Whitfield KC, Bourassa MW, Adamolekun B, Bergeron G, Bettendorff L, Brown KH, Cox L, Fattal-Valevski A, Fischer PR, Frank EL, Hiffler L, Hlaing LM, Jefferds ME, Kapner H, Kounnavong S, Mousavi MPS, Roth DE, Tsaloglou MN, Wieringa F, Combs GF Jr. Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs. Ann N Y Acad Sci. 2018 Oct;1430(1):3-43.
Laird, E.; Molloy, A.M. Water-Soluble Vitamins and Essential Nutrients. Ref. Modul. Biomed. Sci.2014.
Lonsdale D., Vitamin Therapy Paradox: Getting Worse before Getting Better, MARCH 18, 2015, Hormonesmatter.com, accessed 02.02.2023
WHO, Thiamine deficiency and its prevention and control in major emergencies, WHO/NHD/99.13, WHO, 1999
Fattal-Valevski A., Thiamine (Vitamin B1), Journal of Evidence-Based Complementary & Alternative Medicine. 2011;16(1):12-20.
Marrs C, Lonsdale D., Hiding in Plain Sight: Modern Thiamine Deficiency. Cells. 2021 Sep 29;10(10):2595.
The process to determine the effective dose of B1 represents a substantial challenge, as to date there is no standard reference guide which has been tested and validated, on which an estimation of the start dose can be based.
Laboratory tests, such as those checking for thiamine blood levels, play no role in B1 therapy. They do not necessarily reflect “thiamine metabolic function” (Whitfield, 2018) or tissue concentrations. More importantly, thiamine in PD is not used to correct a vitamin deficiency, but is rather given at high, pharmacological doses to overcome a situation in which thiamine metabolic processes are possibly no longer working properly. It has been hypothesised that this could be linked to a series of events which occur in PD (e.g. oxidative stress, neuroinflammation, mitochondrial dysfunction, etc.), which may eventually interfere with the ability of the neuronal cell to produce energy. The section on The Scientific Evidence presents more information on this hypothesis.
Some factors influencing the dose in B1 therapy identified by Dr Costantini in his clinical experience include age, gender, weight, and duration and severity of the disease (Costantini, 2018). More systematic research is needed to confirm this and identify other factors, to standardize the approach and confirm its validity.
It is commonly believed that any excess amount of B1 taken orally - such as the one taken with high-dose B1 therapy - would be eliminated through the urine, B1 being a water-soluble vitamin (Laird, 2014). As such, high doses of thiamine should not lead to any “toxic” or unwanted effect. In short, many believe that an “overdose” of B1 can not occur.
However, in clinical practice, a condition characterized by symptom worsening has been described following high doses of thiamine (“overdose”).
Lonsdale talks about the possibility of patient’s symptoms getting initially worse, unexpectedly, when they are given thiamine i.v. for B1 deficiency. He defines this as a “paradoxical” response, as the patient who is deficient in B1 would paradoxically get worse when receiving it, rather than better. However, this phenomenon would be temporary and eventually “herald a good outcome” (Lonsdale, 2015).
Costantini, using the B1 protocol in PwP, reports that a dose which is too high for a specific individual with PD would cause a worsening of symptoms, after an initial improvement of variable duration - from the same day of administration to usually two weeks. He therefore refers to it as an “overdose”. Stopping B1 for a few days would be accompanied by an improvement of those symptoms without any consequences for the PwP (Costantini, 2018).
As described by Bryan, from anectodal reports (Bryan, 2023, unpublished report), “overdose” symptoms following a dose of B1, are symptoms which:
- are always unpleasant;
- were present before that dosage of B1 and got worse or are new symptoms, e.g. symptoms the PwP had not experienced before that dosage of B1;
- may be perceived as “too much energy”, e.g. jitteriness, feeling of “having had too much coffee”, sleeping problems;
- would usually appear after a period of improvement following that dosage of B1
It is important to emphasise that a dose which may be too high for one PwP (“overdose”), may be right or too low for another one.
The body can store a small amount of B1 - between 30 and 50 mg. If the diet is deficient in thiamine, these limited stores may be depleted within 2-3 week (WHO, 1999; Fattal-Valevski, 2011; Marrs 2021).
So, the approach to one’s searching for the right dose of B1 is at present a trial and error approach. A dose which is too high for a PwP (“overdose”) would cause worsening of symptoms, while a dose which is too low (“underdose”) would produce no effects. To complicate things, the natural progression of the disease may also be responsible for symptoms getting worse. The challenge then consists in the ability to identify the dose which, in that individual person with PD, determines an improvement without causing any worsening of symptoms.
This approach, which requires guidance and support, may otherwise cause some degree of frustration in some PwP, who are very eager to start treatment and may erroneously be lead to believe that a “higher” dose is more “powerful” and better.
Costantini also observed in his clinical practice that, unlike the Italian patients, North-American and African PwP tended to require much lower dosages of B1 and could more easily develop “overdose” symptoms, as quickly as even on the first day of B1 therapy [Costantini, 2018].
Selected references
Costantini and R. Fancellu, Effects of Overdose of High-Dose Thiamine Treatment, Gerontology & Geriatrics Studies, December 06, 2018
Whitfield KC, Bourassa MW, Adamolekun B, Bergeron G, Bettendorff L, Brown KH, Cox L, Fattal-Valevski A, Fischer PR, Frank EL, Hiffler L, Hlaing LM, Jefferds ME, Kapner H, Kounnavong S, Mousavi MPS, Roth DE, Tsaloglou MN, Wieringa F, Combs GF Jr. Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs. Ann N Y Acad Sci. 2018 Oct;1430(1):3-43.
Laird, E.; Molloy, A.M. Water-Soluble Vitamins and Essential Nutrients. Ref. Modul. Biomed. Sci.2014.
Lonsdale D., Vitamin Therapy Paradox: Getting Worse before Getting Better, MARCH 18, 2015, Hormonesmatter.com, accessed 02.02.2023
WHO, Thiamine deficiency and its prevention and control in major emergencies, WHO/NHD/99.13, WHO, 1999
Fattal-Valevski A., Thiamine (Vitamin B1), Journal of Evidence-Based Complementary & Alternative Medicine. 2011;16(1):12-20.
Marrs C, Lonsdale D., Hiding in Plain Sight: Modern Thiamine Deficiency. Cells. 2021 Sep 29;10(10):2595.
Text author: Sergio Pièche
Page updated - 24/04/23
Page updated - 24/04/23