Dr. Weeks’ Comment: Bee venom, IV glutathione*, anti-inflammatory seeds all have promising results with people suffering from Parkinson’s but IM vitamin B1 (thiamin) 100mg once a week is also encouraging !
“… Recent clinical studies showed a considerable and stable improvement of motor and non-motor symptoms in patients affected by PD treated with intramuscular high-dose thiamine (100 mg) administered twice a week (Costantini et al., 2015)…”
“…The administration of high doses of thiamine to patients with PD was effective in reversing the parkinsonian symptoms…”
“…In conclusion, we found that the long-term treatment with the intramuscular administration of thiamine has led to a significant improvement of motor and non-motor symptoms of the patients with PD; this improvement was stable during time and without side effects…”
An open-label pilot study with high-dose thiamine in Parkinson’s disease
Antonio Costantini, M.D. et al
Neural Regen Res. 2016 Mar; 11(3): 406–407. doi: 10.4103/1673-5374.179047PMCID: PMC4828997PMID: 27127471
Parkinson’s disease (PD) is a progressive neurodegenerative disorder clinically characterized by motor symptoms (bradykinesia, tremor, rigidity, postural instability) and non-motor symptoms (hyposmia, sleep disorders, autonomic and sphincteric dysfunctions, fatigue, pain, depression, and cognitive disorders) (Sprenger and Poewe, 2013). The neuropathological hallmark of PD is the degeneration of the pigmented dopaminergic neurons in the substantia nigra; other nuclei involved in neurodegeneration are locus coeruleus, reticular nuclei of brain stem, dorsal motor nucleus of vagus, basal nucleus of Meynert, amygdala, CA2 area of hippocampus, and frontal cortex. At the onset of parkinsonian symptoms, the neuronal loss is quite 70% in the lateral ventral part and 50% in the caudal part of the substantia nigra(Kordower et al., 2013). For this reason, and for the long time between the cellular onset and the clinical onset of the disease, it is mandatory to develop new therapies with disease-modifying and neuroprotective actions. The gold standard therapy for PD is always levodopa, while other currently validated treatments are dopamine agonists, cathecol-O-methyltransferase inhibitors, monoamine-oxidase-B inhibitors, and amantadine (Poewe et al., 2010; Sprenger and Poewe, 2013).
Recent data showed that in some inherited and degenerative diseases of the nervous system the pathogenesis of the symptoms could be linked to a focal deficiency of thiamine (vitamin B1) due either to dysfunction of the intracellular thiamine transport or to structural enzymatic abnormalities. Thiamine is a cofactor of enzymes involved in fundamental pathways of the energetic cell metabolism, particularly critical in glucose metabolism. Thiamine deficiency (TD) is a complication of severe malnutrition associated with chronic alcoholism, HIV-AIDS, and gastrointestinal disease, frequently resulting in Wernicke-Korsakoff encephalopathy, a subacute neurologic disorder characterized by ophthalmoplegia, gait ataxia, confusion, and memory loss (Butterworth, 2003). TD pathophysiology involves several events and results in focal neuronal cell death. Such events, e.g., the reduced activity of alpha-keto-glutarate dehydrogenase, the impaired oxidative metabolism, the increased oxidative stress, and the selective neuronal loss in specific brain regions, represent also some pathological mechanisms involved in the neurodegenerative diseases. TD reduces the activity of the thiamine-dependent enzymes with regional selectivity, being different cerebral areas affected with different severity (Butterworth, 2003). TD could then be an useful model in neurodegeneration (Jhala and Hazell, 2011). New studies suggest that thiamine has also non-coenzymatic roles, potentially relevant in neuroprotection (Mkrtchyan, 2015)…..
…. Several studies demonstrated a link between PD and thiamine (Lu’o’ng and Nguyên, 2011). A decreased activity of the thiamine-dependent enzymes and a selective loss of the mitochondrial complex I have been reported in the nigral neurons of patients with PD (Butterworth, 2003; Schapira, 2014). In the cerebrospinal fluid of patients with PD, free thiamine levels are lower than controls (Jiménez-Jiménez et al., 1999). Experimental findings showed an increased dopamine release in rat striatum after the intrastriatal thiamine administration. In the brain of patients with PD, a reduction in glucose metabolism and an increase of oxidative stress have been reported; in fact, the thiamine-dependent processes are critical in the glucose metabolism, and recent studies implicate thiamine in the oxidative stress, the protein processing, the peroxisomal function, and the gene expression (Brandis et al., 2006; Jhala and Hazell, 2011). Moreover, an interesting study about an alpha-synuclein fission yeast model found that thiamine lowers the alpha-synuclein expression in a dose-dependent manner and that A53T mutated alpha-synuclein aggregates at lower concentrations than wild-type alpha-synuclein: these data suggest that increasing intracellular thiamine could reduce the alpha-synuclein concentration and then the alpha-synuclein aggregation (Brandis et al., 2006). Furthermore, a dysfunction of the intracellular thiamine functions has been described in some genetic diseases characterized by mutations in genes coding for thiamine transporters or thiamine metabolism enzymes, while several inborn metabolic diseases clinically improved after the administration of pharmacological doses of thiamine, such as in Wernicke-like encephalopathy (Kono et al., 2009). However, the role played by thiamine in PD pathogenesis has not yet been extensively investigated.
The administration of high doses of thiamine to patients with PD was effective in reversing the parkinsonian symptoms; we then suppose that the parenteral thiamine supplementation may play an important role in restoring the survivor neurons and in limiting the disease progression, and that the dysfunction of the thiamine-dependent processes could be a primary pathogenic pathway leading to the death of dopaminergic and non-dopaminergic neurons in PD.
The thiamine-dependent processes are impaired in the cerebral tissues of patients with several neurodegenerative diseases and the activity reduction of the thiamine-dependent enzymes can be readily linked to the symptomatology and the pathology of the disorders. Most neurodegenerative diseases share then similarities and could be responsive to high doses of thiamine (Butterworth, 2003; Jhala and Hazell, 2011; Lu’o’ng and Nguyên, 2012; Costantini et al., 2015; Mkrtchyan et al., 2015).
In conclusion, we found that the long-term treatment with the intramuscular administration of thiamine has led to a significant improvement of motor and non-motor symptoms of the patients with PD; this improvement was stable during time and without side effects. Our report represents an important contribution to PD therapy, although further experience is necessary to exclude the placebo effect and to confirm the present observation, with clinical, cellular, and molecular data. The aim of the future studies will be to investigate the clinical, restorative, and neuroprotective effects of the long-term treatment with thiamine in PD.
*600mg- 1000mg in 10 cc of normal saline IV push over 15 minutes three times a week