Parkinson’s disease: a “functional” thiamine deficiency?
E. Overton, a nutritionist with a special interest in thiamine, appreciating Dr Costantini’s intuition, has recently revisited Costantini’s hypothesis (Overton, 2020).
Overton suggests that the cascade of events leading to neuronal death and PD’s symptoms, including among others toxicity, chronic oxidative stress and chronic neuro-inflammation, would lead to inactivation of thiamine-dependent enzymes causing a “metabolic block”.
Among the enzymes involved is the alpha ketoglutarate dehydrogenase (KGDH) which plays a key role in mitochondrial energy metabolism. Its activity is decreased in the substantia nigra of patients with Parkinson's disease (PD).
The block of energy production would then clinically mimic thiamine deficiency. As the thiamine levels are normal, unlike a real deficiency when the levels of thiamine would be low, this block would represent a “functional” thiamine deficiency which is potentially reversible.
Thiamine given at very high doses would then act as a “metabolic stimulant” and be able to overcome thiamine-dependent enzymes inactivation.
Elliot refers also to a study conducted in rats showing that high doses of thiamine, administered before a traumatic brain injury, had a protective role against the effects of oxidative stress caused by the injury on thiamine-dependent enzymatic processes - especially the KGDH enzyme (Mkrtchyan, 2018). Elliot observes that, as the rats did not have thiamine deficiency, the role of high doses of thiamine was not to replenish depleted reserves of the vitamin but rather to reverse the “block”.
He summarize the key point with the title of his article: “Mega-Dose Thiamine: Beyond addressing “deficiency”.
Selected references
Elliot Overton, Nov 18, 2020, Updated: Jan 12, Mega-Dose Thiamine: Beyond Addressing “Deficiency”, accessed 24.12.2022
Garik V Mkrtchyan, Muammer Üçal, Andrea Müllebner, Sergiu Dumitrescu, Martina Kames, Rudolf Moldzio, Marek Molcanyi, Samuel Schaefer, Adelheid Weidinger, Ute Schaefer, Juergen Hescheler, Johanna Catharina Duvigneau, Heinz Redl, Victoria I Bunik, Andrey V Kozlov, Thiamine preserves mitochondrial function in a rat model of traumatic brain injury, preventing inactivation of the 2-oxoglutarate dehydrogenase complex, Biochim Biophys Acta Bioenerg. 2018 Sep;1859(9):925-931.
Overton suggests that the cascade of events leading to neuronal death and PD’s symptoms, including among others toxicity, chronic oxidative stress and chronic neuro-inflammation, would lead to inactivation of thiamine-dependent enzymes causing a “metabolic block”.
Among the enzymes involved is the alpha ketoglutarate dehydrogenase (KGDH) which plays a key role in mitochondrial energy metabolism. Its activity is decreased in the substantia nigra of patients with Parkinson's disease (PD).
The block of energy production would then clinically mimic thiamine deficiency. As the thiamine levels are normal, unlike a real deficiency when the levels of thiamine would be low, this block would represent a “functional” thiamine deficiency which is potentially reversible.
Thiamine given at very high doses would then act as a “metabolic stimulant” and be able to overcome thiamine-dependent enzymes inactivation.
Elliot refers also to a study conducted in rats showing that high doses of thiamine, administered before a traumatic brain injury, had a protective role against the effects of oxidative stress caused by the injury on thiamine-dependent enzymatic processes - especially the KGDH enzyme (Mkrtchyan, 2018). Elliot observes that, as the rats did not have thiamine deficiency, the role of high doses of thiamine was not to replenish depleted reserves of the vitamin but rather to reverse the “block”.
He summarize the key point with the title of his article: “Mega-Dose Thiamine: Beyond addressing “deficiency”.
Selected references
Elliot Overton, Nov 18, 2020, Updated: Jan 12, Mega-Dose Thiamine: Beyond Addressing “Deficiency”, accessed 24.12.2022
Garik V Mkrtchyan, Muammer Üçal, Andrea Müllebner, Sergiu Dumitrescu, Martina Kames, Rudolf Moldzio, Marek Molcanyi, Samuel Schaefer, Adelheid Weidinger, Ute Schaefer, Juergen Hescheler, Johanna Catharina Duvigneau, Heinz Redl, Victoria I Bunik, Andrey V Kozlov, Thiamine preserves mitochondrial function in a rat model of traumatic brain injury, preventing inactivation of the 2-oxoglutarate dehydrogenase complex, Biochim Biophys Acta Bioenerg. 2018 Sep;1859(9):925-931.
Text author: Sergio Pièche
Page updated - 24/04/23
Page updated - 24/04/23
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