ORAL ROUTE
Later, Dr Costantini started PwP also on oral thiamine. The oral route has the advantage over the intramuscular route of ease of administration and good tolerance. However, thiamine (B1) bioavailability is low when it is taken orally, meaning little of the dose taken is absorbed. Also, the majority of PwP have gastrointestinal problems which may affect oral absorption (Skjærbæk, 2021).
It is poorly understood whether at such high unabsorbed amounts, thiamine has any effects on the intestinal microbioma (Lonsdale, 2018).
Dr Costantini estimated that a weekly i.m. dose of 100 mg would be equivalent to an oral dose as high as 140 times; e.g. 100 mg i.m. would correspond to oral 14,000 mg/week = 2,000 mg/day (Costantini, 2018).
In healthy individuals, oral thiamine absorption has been estimated to be between 3.7% and 5.3% (Tallaksen, 1993; Smithline, 2012).
However, it is not known how these findings may apply to PwP, as the presence of gastro-intestinal dysfunction in PwP may influence absorption of medicines (Skjærbæk, 2021).
Thiamine (B1) is absorbed in the intestine (jejunum) by two processes (Smithline, 2012; Marrs, 2021):
In a pharmacokinetics study in healthy persons in whom oral thiamine hydrochloride (HCL) was given at three dosage levels – namely, 100 mg, 500 mg and 1,500 mg, Smithline et al. found that high blood levels of thiamine can be reached quickly with oral HCL. They showed that thiamine intestinal absorption mechanism is not saturable up to the dose tested in the study (1,500 mg) and that a combination of passive and active transport is likely to occur at high doses (Smithline, 2012). Although both mechanisms are likely to work with any dose, pharmacokinetic studies suggest that the active process occurs mainly at low concentrations, while passive diffusion occurs at higher concentrations (Smithline, 2012).
In another study, Baines and colleagues measured the erythrocyte levels of the physiologically active form of thiamine, thiamine diphosphate (ETDP), in 25 alcoholics admitted to hospital, before, during and after supplementation given orally or parenterally. After receiving the dose of 250 mg of thiamine daily for 5 days, both treated groups (oral and parenteral) showed a significant increase in their mean ETDP levels. The authors concluded that, except for urgent cases, oral supplementation achieves the same results as the parenteral one (Baines, 1988).
No difference between the i.m. and oral routes of thiamine (B1) administration in reaching steady state were found by Royer-Morrot et al. (7 and 5.6 days, respectively). They measured plasma thiamine concentrations after administering it by the two routes for 11 days in 20 healthy men: 500 mg thiamine i.m. once a day and 250 mg orally every 12 h. The minimum steady-state concentration achieved by the oral group was 78% of that of the intramuscular group (Royer-Morrot, 1992).
Further evidence about oral vs parenteral route of thiamine comes from a study by Tallaksen and collaborators, who measured concentrations of thiamine and thiamine monophosphate and diphosphate in plasma and whole blood samples in six healthy subjects, after an i.v. and oral dose of 50 mg thiamine HCl. After oral administration, the peak thiamine concentration in plasma was reached after 53 min. Thiamine bioavailability was 5.3%.
Again, also in these cases, it is uncertain whether the study findings can be extrapolated to PwP, due to the gastrointestinal dysfunction frequently present in PD.
Dr Costantini advised PwP to take B1 preferably in divided doses during the day. This advice is supported by a study in which it was found that taking thiamine orally in divided doses significantly increased thiamine absorption. In this study, Morrison et al. gave oral doses of one to 20 mg of thiamine to six normal male persons. The level of urinary excretion of thiamine was used as evidence of thiamine absorption, with a higher excretion indicating a higher absorption. Urinary excretion of thiamine after a 10 mg dose was increased markedly, by threefold, when the vitamin was given in four divided doses of 2.5 mg each at two-hour intervals, compared to when it was given in one single dose of 10 mg only (Morrison, 1960).
Given the gastro-intestinal issues which occur in PD, there is a need for pharmacokinetics studies on thiamine to be specifically conducted in PwP, identifying ways to predict the expected oral absorption rate in individual PwP. This information would assist in deciding which route of administration to use in a single PwP.
Selected references
Skjærbæk C, Knudsen K, Horsager J, Borghammer P. Gastrointestinal Dysfunction in Parkinson's Disease. J Clin Med. 2021 Jan 31;10(3):493.
Lonsdale D, Thiamine and the Microbiome, Hormones Matter, March 5, 2018, accessed 08.03.2023.
Costantini and R. Fancellu, Effects of Overdose of High-Dose Thiamine Treatment, Gerontology & Geriatrics Studies, December 06, 2018
Tallaksen CM, Sande A, Bøhmer T, Bell H, Karlsen J. Kinetics of thiamin and thiamin phosphate esters in human blood, plasma and urine after 50 mg intravenously or orally. Eur J Clin Pharmacol. 1993;44(1):73-8.
Smithline HA, Donnino M, Greenblatt DJ. Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects. BMC Clin Pharmacol. 2012 Feb 4;12:4.
Marrs C, Lonsdale D., Hiding in Plain Sight: Modern Thiamine Deficiency. Cells. 2021 Sep 29;10(10):2595.
Baines M, Bligh JG, Madden JS. Tissue thiamin levels of hospitalised alcoholics before and after oral or parenteral vitamins. Alcohol Alcohol. 1988;23(1):49-52. PMID: 3358822.
Royer-Morrot MJ, Zhiri A, Paille F, Royer RJ. Plasma thiamine concentrations after intramuscular and oral multiple dosage regimens in healthy men. Eur J Clin Pharmacol. 1992;42:219–222.
A. B. Morrison, J. A. Campbell, Vitamin Absorption Studies: I. Factors Influencing the Excretion of Oral Test Doses of Thiamine and Riboflavin by Human Subjects, The Journal of Nutrition, Volume 72, Issue 4, December 1960, Pages 435–440
It is poorly understood whether at such high unabsorbed amounts, thiamine has any effects on the intestinal microbioma (Lonsdale, 2018).
Dr Costantini estimated that a weekly i.m. dose of 100 mg would be equivalent to an oral dose as high as 140 times; e.g. 100 mg i.m. would correspond to oral 14,000 mg/week = 2,000 mg/day (Costantini, 2018).
In healthy individuals, oral thiamine absorption has been estimated to be between 3.7% and 5.3% (Tallaksen, 1993; Smithline, 2012).
However, it is not known how these findings may apply to PwP, as the presence of gastro-intestinal dysfunction in PwP may influence absorption of medicines (Skjærbæk, 2021).
Thiamine (B1) is absorbed in the intestine (jejunum) by two processes (Smithline, 2012; Marrs, 2021):
- an active process – which is saturable and implemented by two carriers, thiamine transporter-1 (SLC19A2) and thiamine transporter-2 (SLC19A3), and
- passive diffusion – which is not saturable.
In a pharmacokinetics study in healthy persons in whom oral thiamine hydrochloride (HCL) was given at three dosage levels – namely, 100 mg, 500 mg and 1,500 mg, Smithline et al. found that high blood levels of thiamine can be reached quickly with oral HCL. They showed that thiamine intestinal absorption mechanism is not saturable up to the dose tested in the study (1,500 mg) and that a combination of passive and active transport is likely to occur at high doses (Smithline, 2012). Although both mechanisms are likely to work with any dose, pharmacokinetic studies suggest that the active process occurs mainly at low concentrations, while passive diffusion occurs at higher concentrations (Smithline, 2012).
In another study, Baines and colleagues measured the erythrocyte levels of the physiologically active form of thiamine, thiamine diphosphate (ETDP), in 25 alcoholics admitted to hospital, before, during and after supplementation given orally or parenterally. After receiving the dose of 250 mg of thiamine daily for 5 days, both treated groups (oral and parenteral) showed a significant increase in their mean ETDP levels. The authors concluded that, except for urgent cases, oral supplementation achieves the same results as the parenteral one (Baines, 1988).
No difference between the i.m. and oral routes of thiamine (B1) administration in reaching steady state were found by Royer-Morrot et al. (7 and 5.6 days, respectively). They measured plasma thiamine concentrations after administering it by the two routes for 11 days in 20 healthy men: 500 mg thiamine i.m. once a day and 250 mg orally every 12 h. The minimum steady-state concentration achieved by the oral group was 78% of that of the intramuscular group (Royer-Morrot, 1992).
Further evidence about oral vs parenteral route of thiamine comes from a study by Tallaksen and collaborators, who measured concentrations of thiamine and thiamine monophosphate and diphosphate in plasma and whole blood samples in six healthy subjects, after an i.v. and oral dose of 50 mg thiamine HCl. After oral administration, the peak thiamine concentration in plasma was reached after 53 min. Thiamine bioavailability was 5.3%.
Again, also in these cases, it is uncertain whether the study findings can be extrapolated to PwP, due to the gastrointestinal dysfunction frequently present in PD.
Dr Costantini advised PwP to take B1 preferably in divided doses during the day. This advice is supported by a study in which it was found that taking thiamine orally in divided doses significantly increased thiamine absorption. In this study, Morrison et al. gave oral doses of one to 20 mg of thiamine to six normal male persons. The level of urinary excretion of thiamine was used as evidence of thiamine absorption, with a higher excretion indicating a higher absorption. Urinary excretion of thiamine after a 10 mg dose was increased markedly, by threefold, when the vitamin was given in four divided doses of 2.5 mg each at two-hour intervals, compared to when it was given in one single dose of 10 mg only (Morrison, 1960).
Given the gastro-intestinal issues which occur in PD, there is a need for pharmacokinetics studies on thiamine to be specifically conducted in PwP, identifying ways to predict the expected oral absorption rate in individual PwP. This information would assist in deciding which route of administration to use in a single PwP.
Selected references
Skjærbæk C, Knudsen K, Horsager J, Borghammer P. Gastrointestinal Dysfunction in Parkinson's Disease. J Clin Med. 2021 Jan 31;10(3):493.
Lonsdale D, Thiamine and the Microbiome, Hormones Matter, March 5, 2018, accessed 08.03.2023.
Costantini and R. Fancellu, Effects of Overdose of High-Dose Thiamine Treatment, Gerontology & Geriatrics Studies, December 06, 2018
Tallaksen CM, Sande A, Bøhmer T, Bell H, Karlsen J. Kinetics of thiamin and thiamin phosphate esters in human blood, plasma and urine after 50 mg intravenously or orally. Eur J Clin Pharmacol. 1993;44(1):73-8.
Smithline HA, Donnino M, Greenblatt DJ. Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects. BMC Clin Pharmacol. 2012 Feb 4;12:4.
Marrs C, Lonsdale D., Hiding in Plain Sight: Modern Thiamine Deficiency. Cells. 2021 Sep 29;10(10):2595.
Baines M, Bligh JG, Madden JS. Tissue thiamin levels of hospitalised alcoholics before and after oral or parenteral vitamins. Alcohol Alcohol. 1988;23(1):49-52. PMID: 3358822.
Royer-Morrot MJ, Zhiri A, Paille F, Royer RJ. Plasma thiamine concentrations after intramuscular and oral multiple dosage regimens in healthy men. Eur J Clin Pharmacol. 1992;42:219–222.
A. B. Morrison, J. A. Campbell, Vitamin Absorption Studies: I. Factors Influencing the Excretion of Oral Test Doses of Thiamine and Riboflavin by Human Subjects, The Journal of Nutrition, Volume 72, Issue 4, December 1960, Pages 435–440
Text author: Sergio Pièche
Page updated - 24/04/23
Page updated - 24/04/23