Thiamine role in Parkinson's Disease
A. Costantini, R. Fancellu, An open-label pilot study with high-dose thiamine in Parkinson’s disease. Neural Regen Res. 2016, 11(3):406-407.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828997/
In this paper, Costantini and Fancellu give a possible interpretation about the role of thiamine in Parkinson’s, to explain why thiamine administered at high doses would result in symptom improvement.
Role of thiamine - Thiamine is a cofactor of many enzymes which are involved in energy cell metabolism and in oxidative metabolism (transketolase, alpha-keto-acid decarboxylase, pyruvate dehydrogenase, alpha-keto-glutarate dehydrogenase). A cofactor is a “helper” which “assists” enzymes in biochemical reactions. So, thiamine is critical for metabolic processes which produce the energy that the cell needs; it is essential in glucose metabolism, which has been reported to be reduced in PwP’s brains. A deficiency in thiamine would have serious consequences for the cell.
Recent studies suggest that thiamine has also non-coenzymatic roles, which may play a role in neuroprotection.
Consequences of thiamine deficiency - Costantini and Fancellu suggest that, as a result of events occurring in PD, a “dysfunction of the intracellular thiamine transport or structural enzymatic abnormalities” could occur and lead to thiamine deficiency.
This deficiency would however occur selectively only in some areas of the brain of PwP, which are the areas most affected by the disease.
A deficiency in thiamine, the inability of the transport system in the cell to take thiamine where it is needed or enzymatic abnormalities would in these brain areas slow down key biochemical reactions which depend on thiamine to produce energy. This situation would represent a major challenge to cell survival, eventually resulting in neuronal death and PD symptoms.
Supporting evidence - In support of this theory on thiamine deficiency in PD, Costantini and Fancellu report an increasing body of evidence from findings from several studies.
One of them is the finding of reduced activities of thiamine-dependent enzymes in brains of thiamine deficiency animal models and in the substantia nigra of PwP.
Another finding concerns the presence of lower levels of free thiamine in PwP’s cerebrospinal fluid than those in people without PD.
Several studies have also demonstrated a link between PD and thiamine (Khanh vinh quôc Lu'o'ng and Lan Thi Hoàng Nguyên, 2012) and an increase in dopamine release was observed in a rat model study in which thiamine was administered in the striata.
Furthermore, intracellular thiamine functions have been found disrupted in some genetic diseases affecting thiamine transporters or thiamine metabolism enzymes.
Finally, fission yeast model data have suggested that “increasing intracellular thiamine could reduce alpha-synuclein concentration and alpha-synuclein aggregation” (K. A. Brandis et al., 2006).
Effect of administration of high doses of thiamine - The administration of high, supra-physiological doses of thiamine would, through passive diffusion, add thiamine to the cell and the mitochondria, overcoming the dysfunctions described above and causing symptom improvement through:
a) an increase in the activity of thiamine-dependent enzymatic processes in the areas affected by PD, reactivating the energy metabolism, and
b) an increase in dopamine or better utilization of the exogenous levodopa.
Selected references
Khanh vinh quôc Lu'o'ng 1, Lan Thi Hoàng Nguyên, Thiamine and Parkinson's disease, J Neurol Sci. 2012 May 15;316(1-2):1-8
Katrina A Brandis, Isaac F Holmes, Samantha J England, Nijee Sharma, Lokesh Kukreja, Shubhik K DebBurman, alpha-Synuclein fission yeast model: concentration-dependent aggregation without plasma membrane localization or toxicity, J Mol Neurosci. 2006;28(2):179-91
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828997/
In this paper, Costantini and Fancellu give a possible interpretation about the role of thiamine in Parkinson’s, to explain why thiamine administered at high doses would result in symptom improvement.
Role of thiamine - Thiamine is a cofactor of many enzymes which are involved in energy cell metabolism and in oxidative metabolism (transketolase, alpha-keto-acid decarboxylase, pyruvate dehydrogenase, alpha-keto-glutarate dehydrogenase). A cofactor is a “helper” which “assists” enzymes in biochemical reactions. So, thiamine is critical for metabolic processes which produce the energy that the cell needs; it is essential in glucose metabolism, which has been reported to be reduced in PwP’s brains. A deficiency in thiamine would have serious consequences for the cell.
Recent studies suggest that thiamine has also non-coenzymatic roles, which may play a role in neuroprotection.
Consequences of thiamine deficiency - Costantini and Fancellu suggest that, as a result of events occurring in PD, a “dysfunction of the intracellular thiamine transport or structural enzymatic abnormalities” could occur and lead to thiamine deficiency.
This deficiency would however occur selectively only in some areas of the brain of PwP, which are the areas most affected by the disease.
A deficiency in thiamine, the inability of the transport system in the cell to take thiamine where it is needed or enzymatic abnormalities would in these brain areas slow down key biochemical reactions which depend on thiamine to produce energy. This situation would represent a major challenge to cell survival, eventually resulting in neuronal death and PD symptoms.
Supporting evidence - In support of this theory on thiamine deficiency in PD, Costantini and Fancellu report an increasing body of evidence from findings from several studies.
One of them is the finding of reduced activities of thiamine-dependent enzymes in brains of thiamine deficiency animal models and in the substantia nigra of PwP.
Another finding concerns the presence of lower levels of free thiamine in PwP’s cerebrospinal fluid than those in people without PD.
Several studies have also demonstrated a link between PD and thiamine (Khanh vinh quôc Lu'o'ng and Lan Thi Hoàng Nguyên, 2012) and an increase in dopamine release was observed in a rat model study in which thiamine was administered in the striata.
Furthermore, intracellular thiamine functions have been found disrupted in some genetic diseases affecting thiamine transporters or thiamine metabolism enzymes.
Finally, fission yeast model data have suggested that “increasing intracellular thiamine could reduce alpha-synuclein concentration and alpha-synuclein aggregation” (K. A. Brandis et al., 2006).
Effect of administration of high doses of thiamine - The administration of high, supra-physiological doses of thiamine would, through passive diffusion, add thiamine to the cell and the mitochondria, overcoming the dysfunctions described above and causing symptom improvement through:
a) an increase in the activity of thiamine-dependent enzymatic processes in the areas affected by PD, reactivating the energy metabolism, and
b) an increase in dopamine or better utilization of the exogenous levodopa.
Selected references
Khanh vinh quôc Lu'o'ng 1, Lan Thi Hoàng Nguyên, Thiamine and Parkinson's disease, J Neurol Sci. 2012 May 15;316(1-2):1-8
Katrina A Brandis, Isaac F Holmes, Samantha J England, Nijee Sharma, Lokesh Kukreja, Shubhik K DebBurman, alpha-Synuclein fission yeast model: concentration-dependent aggregation without plasma membrane localization or toxicity, J Mol Neurosci. 2006;28(2):179-91
Text author: Sergio Pièche
Page updated - 24/04/23
Page updated - 24/04/23
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