Lithium Orotate for Depression and more?
So I was watching this video on lithium orotate (still looking to get past my depression) and was amazed at the way he says lithium works in the brain. Lithium clears glutamate?
Anybody up for lowering inflammation? Boosting neuroplasticity?
And then he starts going through the other supplements work well with LO: Inositol, NAC, Taurine, Vitamin C, Meditation, etc...
Thanks for sharing
Thanks for the Peter Smith video. Very informative
Interesting 🤔
Are you taking it already, Bolt? bass mentioned a fairly quick response to LO once he found an optimal dose.
Art
5 mg tabs/caps arriving tomorrow. Hopefully this, plus Prozac, plus Inositol, plus L Methylfolate can clear this depression. Thank you for asking.
2 weeks at optimal dose for me
i had been taking lithuium oratate for more than a year as recommended by bass of spades who learned about it from Dr Mischley. I was getting good results for whatever I am experiencing (I thought it was anxiety but perhaps it was depression). So the stuff works on me. But then I was told by Dr Rogers(Inova) that Lithium might cause tremor to increase so I became scared and tapered myself off it. Now I watched the video and think the positives must outweigh any negatives and my anxiety has returned. So I am considering restarting. I already have the pills. Does anyone know whether it increases tremor for real??? Best to you Dave! Thanks for your excellent posts.
inova.org/doctors/sean-l-ro...
It does not increase tremors for me . More likely the opposite. Glad it helps you . Btw it was recommended to me by Dr S Todd Robinson , not Dr Mischley. Dr Mischley is cited numerous times in the book Dr Robinson made me read though.
Thanks for the video.
Lithium beyond psychiatric indications: the reincarnation of a new old drug 2021 ncbi.nlm.nih.gov/labs/pmc/a...
"Abstract
Lithium has been used in the treatment of bipolar disorders for decades, but the exact mechanisms of action remain elusive to this day. Recent evidence suggests that lithium is critically involved in a variety of signaling pathways affecting apoptosis, inflammation, and neurogenesis, all of which contributing to the complex pathophysiology of various neurological diseases. As a matter of fact, preclinical work reports both acute and long-term neuroprotection in distinct neurological disease models such as Parkinson’s disease, traumatic brain injury, Alzheimer’s disease, and ischemic stroke. Lithium treatment reduces cell injury, decreases α-synuclein aggregation and Tau protein phosphorylation, modulates inflammation and even stimulates neuroregeneration under experimental conditions of Parkinson’s disease, traumatic brain injury, and Alzheimer’s disease. The therapeutic impact of lithium under conditions of ischemic stroke was also studied in numerous preclinical in vitro and in vivo studies, giving rise to a randomized double-blind clinical stroke trial. The preclinic data revealed a lithium-induced upregulation of anti-apoptotic proteins such as B-cell lymphoma 2, heat shock protein 70, and activated protein 1, resulting in decreased neuronal cell loss. Lithium, however, does not only yield postischemic neuroprotection but also enhances endogenous neuroregeneration by stimulating neural stem cell proliferation and by regulating distinct signaling pathways such as the RE1-silencing transcription factor. In line with this, lithium treatment has been shown to modulate postischemic cytokine secretion patterns, diminishing microglial activation and stabilizing blood-brain barrier integrity yielding reduced levels of neuroinflammation. The aforementioned observations culminated in a first clinical trial, which revealed an improved motor recovery in patients with cortical stroke after lithium treatment. Beside its well-known psychiatric indications, lithium is thus a promising neuroprotective candidate for the aforementioned neurological diseases. A detailed understanding of the lithium-induced mechanisms, however, is important for prospective clinical trials which may pave the way for a successful bench-to-bedside translation in the future. In this review, we will give an overview of lithium-induced neuroprotective mechanisms under various pathological conditions, with special emphasis on ischemic stroke."
Searching on Lithium and Parkinson's you find some articles questioning whether people with Bipolar Disease have a higher incidence of PD due to their taking Lithium. This article calmed my fears a bit (please do your own research):
Bipolar Disorder and Parkinson's Disease: A 123I-Ioflupane Dopamine Transporter SPECT Study 2021 frontiersin.org/articles/10...
"Objectives: Bipolar disorder (BD) has been suggested to be a risk factor for the development of Parkinson's disease (PD). Standard treatment of BD includes drugs that are known to induce drug-induced parkinsonism (DIP). Clinical differentiation between PD and DIP is crucial and might be aided by functional neuroimaging of the dopaminergic nigrostriatal pathway.
Methods: Twenty consecutive BD patients with parkinsonism were clinically assessed and underwent 123I-ioflupane dopamine transporter single-photon emission computer tomography (SPECT). Imaging data of BD patients with pathological scans were further compared to a population of 40 de novo PD patients.
Results: Four BD patients had abnormal scans, but their clinical features and cumulative exposure to both antipsychotic drugs and lithium were similar to those of BD patients with normal dopamine transporter imaging. BD patients with pathological scans had putaminal binding ratio and putamen-to-caudate ratios higher than those of PD patients despite a similar motor symptom burden.
Conclusions: Up to 20% of BD patients with parkinsonism might have an underlying dopaminergic deficit, which would not be due to cumulative exposure to offending drugs and is ostensibly higher than expected in the general population. This supports the evidence that BD represents a risk factor for subsequent development of neurodegenerative parkinsonism, the nature of which needs to be elucidated."
Translational evidence for lithium-induced brain plasticity and neuroprotection in the treatment of neuropsychiatric disorders 2021 nature.com/articles/s41398-...
"Lithium in neurodegenerative and psychiatric disorders Neurodegenerative disorders: AD and PD and ALS/FTD
A growing body of evidence points to the neuroprotective effects of Li+. Subjects with BD administered with long-term Li+ have a lower risk to develop dementia including AD [53, 54]. A meta-analysis study [55] shows that Li+ treatment significantly decreases cognitive decline as compared with placebo, thus indicating that Li+ may be beneficial in promoting cognitive performance in subjects with mild cognitive impairment (MCI) and AD.
Li+ may act at multiple steps within the biochemical cascades involved in the onset and progression of AD (Fig. 1). For instance, GSK-3β inhibition may counteract the pathological increased enzyme activity occurring in patients affected by MCI and AD [56]. GSK-3β is involved in amyloidogenesis and tau phosphorylation, which at the preclinical level are inhibited by Li+ administration [57]. Again, Li+-induced autophagy may counteract autophagy suppression, which is expected in AD patients due to a progressive increase in mTOR activity during the disease course [35, 58]. Moreover, Li+ promotes the synthesis and release of neurotrophic factors, in particular BDNF and VEGF whose increased availability protects neurons against neurotoxic insults, stimulates hippocampal neurogenesis, and increases synaptic plasticity [2]. Indeed, BDNF polymorphisms were reported to moderate Aβ-related cognitive decline in preclinical AD [59], and BDNF reduces Aβ in the brain [60]. However, a short half-life and inability to cross the blood–brain barrier impair the therapeutic potential of BDNF [61].
Such a limitation is overcome by small molecules like BDNF mimetic compounds that are able to protect primary neurons from Aβ-induced toxicity and to promote synaptogenesis [62]. Moreover, Li+ is able to effectively activate the molecular pathway increasing BDNF synthesis [10] It is worth noting that animal models play a key role in AD research also fostering clinical studies in patients to assess Li+ efficacy in contrasting Aβ and tau pathology [63].
ALS is a motor neuron disease, belonging to a group of neurological disorders that selectively affect motor neurons controlling voluntary muscles of the body. ALS can be classified as familial or sporadic, depending on whether or not there is a family history of the disease. Although there is no consensus on the familial definition, a number of genes are considered to cause the disease.
Motor symptoms improvement by Li+ was reported during the past two decades. Thus, in a clinical trial, Li+ treatment for 15 months was shown to be safe and significantly associated with a slower rate of disease progression and death [28]. Substantial neuroprotection accompanied by delayed disease onset and increased life span was shown in G93A murine model [28]. It should be pointed out that several ALS genetic murine models have been developed [64]. Although of huge utility in preclinical research, they are partially representative of the pathology and the efficacy of lithium in these models deserves to be further investigated [65].
Daily doses of Li+, leading to plasma levels ranging from 0.4 to 0.8 mM, delay disease progression in a small group of ALS patients [28]. This was further validated in a stratified study on ALS patients carrying the UNC13A variant where Li+ doubles survival time [29], while in a heterogeneous ALS population these protective effects of Li+ are debatable. Thus, it is clear how Li+ affects multiple targets, all of which are likely to contribute to the improvement of ALS, such as autophagy that involves Li+ inhibitory action on GSK-3 and IP3 turnover or suppression of glial cell activation in the spinal cord [4].
Li+ induces autophagy to counteract ER stress and altered UPR and rescues autophagy failure occurring in both ALS/FTD and BD [7, 28, 34, 35, 49, 66,67,68,69,70,71,72]. Noteworthy, UPR markers (p-eIF2a, GRP78, GRP94, XBP1, and CHOP) have been shown to predict Li+ responsiveness in bipolar patients [70].
Li+-responsive psychiatric disorders, such as BD, depression, and anxiety, may often precede ALS/FTD, and patients with psychiatric disorders receiving regular Li+ treatment have a reduced prevalence of ALS and dementia [73].
This evidence shows once more that neurodegenerative diseases and affective disorders may share common neural mechanisms into which Li+ acts as therapeutic, strongly suggesting that these mechanisms are crucial in etiology.
Li+ efficacy in PD has been poorly studied and results indicate that it deserves substantial clinical trials to ascertain promising neuroprotection as suggested by experimental models.
In a parkin mutant transgenic mouse, low doses of Li+ prevent motor impairment as well as dopaminergic striatal degeneration, parkin-induced striatal astrogliosis, and microglial activation. These results further validate Li+ as a potential therapy for PD [74]. At first glance, this may sound odd since Li+ by impeding sensitization produced by DA [75] is expected to attenuate the efficacy of the long-term L-DOPA response, which represents an important part of L-DOPA symptomatic effect. Thus, a symptomatic interference of Li+ with PD may hide the disease-modifying effect produced by Li+ acting on autophagy-dependent ongoing degenerative steps [7, 69].
Alpha-synuclein, a major substrate of autophagy, accumulates in Lewy bodies, which are mostly found within spared dopaminergic neurons of the substantia nigra pars compacta [76], as well as within extra-nigral neuronal populations [77].
Moreover, genetic ablation of Atg7 specifically within DA neurons fully reproduces PD pathology, including the formation of alpha-synuclein-stained Lewy bodies. Evidence that points to a key role of autophagy in DA-related disorders [78] and Li+ as a potential therapy for PD has been provided [4]."
Hey, there is a trial: Effects of Lithium Therapy on Blood-based Therapeutic Targets in Parkinson's Disease clinicaltrials.gov/ct2/show...
"Detailed Description:
Lithium belongs to a class of kinase-targeting therapies, including the diabetes medication exenatide and the cancer medication nilotinib, that have demonstrated promise as disease-modifying therapies for Parkinson's disease (PD). Exenatide was recently shown to engage protein kinase B (Akt) and provide significant symptomatic and possible disease-modifying benefit in PD in a phase 2 randomized controlled trial (RCT). Nilotinib engages c-Abelson kinase (c-Abl) and its disease-modifying effects are currently being investigated in two, phase 2 PD RCTs. Lithium targets Akt, glycogen synthase kinase-3 beta (GSK-3B, a downstream target of Akt) and cyclin-dependent kinase 5 (cdk5, a downstream target of c-Abl) in manners that recapitulate those of exenatide and nilotinib. Also, lithium inhibits inositol monophosphate leading to enhanced autophagy and reduced intracellular levels of alpha-synuclein (a-synuclein), which is believed to be a primary mediator of the progressive neurodegeneration in PD. In addition to a-synuclein, genome-wide association studies (GWAS) have implicated oligomeric tau in the pathogenesis of PD. Pathological mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of a late-onset parkinsonism that is clinically indistinguishable from sporadic PD and very similar pathologically. Pathological LRRK2 mutations affect the activities of Akt, GSK-3B and cdk5 to greatly increase the formation of phosphorylated tau (p-tau) - the precursor to tau oligomer formation - and decrease the activity of the transcriptional cofactor B-catenin - which mediates the transcription of neuronal survival genes implicated in PD such as nuclear receptor related 1 (Nurr1). Through its ability to inhibit GSK-3B, lithium can enhance B-catenin-mediated activity and Nurr1 expression. Lithium was also effective in several PD animal models. Finally, both clinical trial and epidemiologic data suggest that lithium exposures of even <1mg a day may provide significant disease-modifying effects in neurodegenerative diseases including PD.
The investigators propose to assess the effects of 3 lithium dosages for 6 months on the above targets measured in blood in a randomized, parallel design, proof of concept clinical trial among 18 PD patients. In addition, 2 PD patients will serve as controls and not receive lithium therapy."
Interesting: The trial is using Lithium Aspartate and Lithium Carbonate. Lithium Aspartate Vs. Lithium Orotate livestrong.com/article/3169... (I verified the reason they chose aspartate was not because they thought it would be more effective than orotate).
There is a lot about a lot in here: Autophagy-Lysosomal Pathway as Potential Therapeutic Target in Parkinson’s Disease 2021 mdpi-res.com/d_attachment/c...
Thank you for this info, Bolt!!!!
A question to lithium users 
Lithium Orate , Taurine
PD and Lithium use
What serum levels indicate someone is deficient in Lithium? 
