100 replies to this topic

[Heh]

I think it's 0.5-1mg/liter in mineral water.

This is strictly a guess from you isn't it? There are so many sources of mineral water that it has to widely vary. Hell, I imagine it varies some even from the same source .....

No, I read it somewhere. I just can't remember where.

[Heh]

Mentally disturbed woman potentially tries to kill herself with LO. Vital signs never changed, she felt ill, threw up once, and all was resolved after some fluids.

It doesn't matter why she took it. She took it and got sick. People shouldn't act like it's as safe as mothers milk, because it isn't. Not for everyone. Looks like it didn't work out so well for Guardian.

I don't think any real claims were made that it was "safe as mother's milk," more that it is safer (at the dosages required) than high doses of Lithium Carbonate.

Mentally disturbed woman potentially tries to kill herself with LO. Vital signs never changed, she felt ill, threw up once, and all was resolved after some fluids.

It doesn't matter why she took it. She took it and got sick. People shouldn't act like it's as safe as mothers milk, because it isn't. Not for everyone. Looks like it didn't work out so well for Guardian.

I don't have a horse in this race but your bias here against LO is remarkable. This so-called "toxicity" amounted to "nausea" after a deliberate overdose. Then you toss in Guardian's anecdotal report which - while I sympathize with him - amounts to "a report on the internet." We all know every single supp discussed on here has somebody claiming it irrevocably changed them. Meanwhile you've handily ignored the journal link I posted in which true toxicity was experienced by a woman taking a therapeutic dose of Lithium carbonate.

I will continue to take 2.5mg LO on a weekly basis as a trace-mineral supplement.

Hmm. I take three and a half times as much LO as you do. Is that indicative of my "bias"? As blood pointed out, trying to get to the truth is not bias. It's science. I don't want this forum to turn into a place where people are handing out medical advice on the basis of "user reviews from shopping sites" (LOL!). Lithium is well known to have a poor therapeutic index. That means that the ratio between the therapeutic dose and the toxic dose is not very large. The fact that toxicity was observed at 900-1200mg is hardly surprising. Seeing toxicity or side effects from LO at much lower doses should tell you that it's not something you can pop like candy. I felt like the drug was being pimped here, and a little balance was needed.

It is important to look at both scientific research and anecdotal user data. That is my point. If you can't understand that, then you will always be behind the curve. Also, you look at those things to kinda gauge safety and effectiveness (both long-term and short-term) to see if it makes sense to try out a new substance. But at the end of the day the data point that matters most (as far as effectiveness of the substance on you) is you. If it works for you where it works for no one else, then all the scientific and anecdotal mumbo jumbo you read that says it won't work means nothing. Vice versa if something that's been proven to work and that works for everyone doesn't work for you.

There are no claims that Lithium Orotate isn't without side-effects, just that it's probably better than the carbonate version. The main side-effects I read about with Lithium Orotate are brain fog and lethargy near the beginning of taking it, and that's usually from taking too much. And also bad skin. Many people take half a pill (of the 4.8mg elemental) a day (5 days a week) for anti-aging/anti-anxiety/brain protection/etc effects without any problems.

You talk about datapoints and strongly imply the stupidity of looking at anecdotal user data in determining the efficacy of a substance, and yet you'd like to throw Guardian's single datapoint (very saddening the effect it had on him/her) in as though that makes the point you're making the irrefutable truth. Guardian probably took too high a dosage of Lithium.

I think the only real point you have is that Lithium Orotate's dosage doesn't have to be very high for it to work well, and I think that's the idea being presented here. Some people messing around with the possibly toxic dosages of Lithium Carbonate could end up taking little more than one of the Lithium Orotate pills to achieve the same effect without the side-effects they suffer on Lithium Carbonate, and without having to constantly monitor their vitals with bloodwork.

Looking at clinical studies alone is no way to get to the truth, isn't the only way to get to the truth, and is definitely no quick way to get to the truth. Many of these substances haven't been formally studied effectively, so it's up to the community to get things moving. Lithium Orotate has been studied and used enough to the point where it's clear that it can be effective and safer for those Bipolar sufferers who respond positively to it (at the right dosage).

In my opinion, you are hiding your BS behind claims that you are about the truth and science. Typical spin to dampen your refuted point and to distract from what you were really trying to do. I am about truth and science, and this is how I go about finding it.

I don't suffer from Bipolar disorder, but I take half a tablet per day (5 days a week) for nootropic benefit. It especially goes well with Pramiracetam. Obviously, if you don't have bipolar disorder, then you shouldn't be taking that many (1-3) of the damn pills.

I think it's 0.5-1mg/liter in mineral water.

This is strictly a guess from you isn't it? There are so many sources of mineral water that it has to widely vary. Hell, I imagine it varies some even from the same source .....

No, I read it somewhere. I just can't remember where.

And for the lazy person that downvoted me because they can't do a simple google search, here are some sites that give information on the concentration of lithium in mineral water:

http://www.lenntech....m-and-water.htm
http://jama.jamanetw...rticleid=352038

I'm rarely on the offensive, mostly the defensive, so I don't have to go out of my way to prove anything. If you don't want to listen to me, then that's fine. But more important than listening or not listening to me is choosing wisely who you listen to, and in this thread those saying Lithium Orotate doesn't work, or those saying that a massive dosage is needed are probably not the ones you want to be listening to. At the dosage (is it 1-2 pills now?) required Lithium Orotate is fairly safe, so you can always try it out (Bipolar people) to see if it works for you. If it doesn't, then you'll know fairly quickly and not a hair will be lost from your head. Also, I still recommend trying resveratrol in addition to whatever you are taking to help ease some of your problems, as many sufferers have reported luck with that.

Edited by Joel, 26 November 2013 - 06:54 PM.

[mikeinnaples]

I think it's 0.5-1mg/liter in mineral water.

This is strictly a guess from you isn't it? There are so many sources of mineral water that it has to widely vary. Hell, I imagine it varies some even from the same source .....

No, I read it somewhere. I just can't remember where.

http://www.mineralwa...rals&parval=Lip

Take a look at this....

[Heh]

I think it's 0.5-1mg/liter in mineral water.

This is strictly a guess from you isn't it? There are so many sources of mineral water that it has to widely vary. Hell, I imagine it varies some even from the same source .....

No, I read it somewhere. I just can't remember where.

http://www.mineralwa...rals&parval=Lip

Take a look at this....

So it looks like a bound of 0-1.1mg/liter would be better (as opposed to 0.5-1mg/liter), with the usual outliers. Either way, this is a better and more specific source, as one can now pick a brand that's in the range being sought.

Edited by Joel, 26 November 2013 - 08:17 PM.

[blood]

Interesting new(ish) study - 300 mcg lithium/ day appears to stabilise cognitive impairment in Alzheimer's patients:

http://www.ncbi.nlm.nih.gov.ezproxy.lib.rmit.edu.au/pubmed/?term=Microdose+lithium+treatment+stabilized+cognitive+impairment+in+patients+with+Alzheimers+disease.

Curr Alzheimer Res. 2013 Jan;10(1):104-7.
Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease.

Nunes MA, Viel TA, Buck HS.

Source

Department of Physiological Sciences, Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo. R. Dr. Cesario Motta Jr, 61, CEP: 01221-020, Sao Paulo, SP, Brazil.

Abstract


A lower incidence of dementia in bipolar patients treated with lithium has been described. This metal inhibits the phosphorylation of glycogen-synthase-kinase 3-α and β, which are related to amyloid precursor protein processing and tau hyperphosphorylation in pathological conditions, respectively. Following the same rationale, a group just found that lithium has disease-modifying properties in amnestic mild cognitive impairment with potential clinical implications for the prevention of Alzheimer's Disease (AD) when a dose ranging from 150 to 600 mg is used. As lithium is highly toxic in regular doses, our group evaluated the effect of a microdose of 300 μg, administered once daily on AD patients for 15 months. In the evaluation phase, the treated group showed no decreased performance in the mini-mental state examination test, in opposition to the lower scores observed for the control group during thetreatment, with significant differences starting three months after the beginning of the treatment, and increasing progressively. This data suggests the efficacy of a microdose lithium treatment in preventing cognitive loss, reinforcing its therapeutic potential to treat AD using very low doses.

PMID: 22746245 [PubMed - indexed for MEDLINE]

[mrd1]

I really like my 750 mg of lithium carbonate / day. No side effects. I personally, would never switch to lithium orotate. I like having a doctor maintain me in a 0.7-0.8 lithium level range for the antidepressant effects w.o the sides.

I really like my 750 mg of lithium carbonate / day. No side effects. I personally, would never switch to lithium orotate. I like having a doctor maintain me in a 0.7-0.8 lithium level range for the antidepressant effects w.o the sides.

[Ark]

I take Lithium Carbonate and trust me I've had LO and LO is not even in the ball park of LC. .........................---- Allot of wishful thinking in this thread backed by outdated studies........*(kinda sad for immisnt/longecity standerds)

[Virtual Reality]

Ive stopped LO, i had been using it for 5 days, around 4 days, i became lethargic. and had a headache, which carried on day 4 and 5. Day 6 i decided to stop it , and the headache was gone. I do feel a bit better now, could it be that lithium was repairing something in my brain, because of the headache?

[blood]

Ive stopped LO, i had been using it for 5 days, around 4 days, i became lethargic. and had a headache, which carried on day 4 and 5. Day 6 i decided to stop it , and the headache was gone. I do feel a bit better now, could it be that lithium was repairing something in my brain, because of the headache?

Maybe 5 mg/day is simply too much for you?

I've seen 1 mg/day proposed as a hypothetical RDA.

You could consider chipping the tablets into 4 pieces - taking just a quarter of a tablet a day. This would provide very roughly 1 mg/day Lithium (instead of 5 mg/ day)?

It only took 0.3 mg/day of lithium to slow down the progression of cognitive impairment in Alzheimer's patients.

[mrd1]

Ok ill bite, maybe lithium orotate in micro doses might do something. My reasoning against my better judgement is that it does have some extremely complex interactions in the brain. I have papers that go on for pages and pages and I struggle to read them. My question is, is there a conversion rate between lithium orotate and carbonate because I strongly believe lithium carbonate could cause dramatic effects either good or bad depending on how its used and by whom.

[blood]

Ok ill bite, maybe lithium orotate in micro doses might do something. My reasoning against my better judgement is that it does have some extremely complex interactions in the brain. I have papers that go on for pages and pages and I struggle to read them. My question is, is there a conversion rate between lithium orotate and carbonate because I strongly believe lithium carbonate could cause dramatic effects either good or bad depending on how its used and by whom.

I wasn't suggesting that higher doses of lithium aren't likely to have beneficial effects. I suggested the previous poster try a lower dose as he/she was complaining of side effects.

This study found doses of 150-600mg/day lithium carbonate (dose adjusted to achieve serum levels of 0.25–0.5 mmol/l) taken long term had some beneficial effects in people with mild cognitive impairment:

Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial

Orestes V. Forlenza, MD, PhD, Breno S. Diniz, MD, Márcia Radanovic, MD, PhD, Franklin S. Santos, MD, PhD, Leda L. Talib, BSc and Wagner F. Gattaz, MD, PhD

Abstract

Background

Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer’s disease, although no benefits were obtained from short-term treatment.

Aims

To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI).

Method

Forty-five participants with aMCI were randomised to receive lithium (0.25–0.5 mmol/l) (n = 24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (Aβ42), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392.

Results

Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P = 0.03) and better performance on the cognitive subscale of the Alzheimer’s Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%.

Conclusions

The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer’s disease.

[blood]

is there a conversion rate between lithium orotate and carbonate

There's not much support for the idea that lithium orotate is more bioavailable than lithium carbonate.... in terms of bioavailability, I suspect your "conversion rate" would be 1 mg lithium as lithium orotate ~= 1 mg lithium as lithium carbonate.

There are historical reasons why "microdose" lithium orotate tablets are available but microdose lithium carbonate tablets are not (e.g., the orotate form in microdose was championed for decades by Hans Neiper). There's no reason why we shouldn't be available to buy microdose lithium as e.g., lithium carbonate. (Except, maybe, lithium carbonate is designated as a drug and therefore requires a prescription in some jurisdictions).

Edited by blood, 18 December 2013 - 06:56 AM.

[Virtual Reality]

Ive stopped LO, i had been using it for 5 days, around 4 days, i became lethargic. and had a headache, which carried on day 4 and 5. Day 6 i decided to stop it , and the headache was gone. I do feel a bit better now, could it be that lithium was repairing something in my brain, because of the headache?

Maybe 5 mg/day is simply too much for you?

I've seen 1 mg/day proposed as a hypothetical RDA.

You could consider chipping the tablets into 4 pieces - taking just a quarter of a tablet a day. This would provide very roughly 1 mg/day Lithium (instead of 5 mg/ day)?

It only took 0.3 mg/day of lithium to slow down the progression of cognitive impairment in Alzheimer's patients.

How long does LO need to be in your system to detect positive benefits anyways?



And yes do u think only 1 mg is helpful? If so I might try a lower dose.

[mrd1]

I would be worried about the safety and accuracy of dosing lithium oratate since, I know if I even just took my lithium carbonate twice I would get hand tremors and be at a increased risk of hypothyroidism. So, I think a very very clear conversion would be needed for anyone trying to replicate the Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial study mentioned. Or, perhaps you can buy lithium carbonate for chemistry use aka not for human consumption. It be pretty annoying if you cant buy some friggin lithium carbonate yet buy analogs of dmt and benzos lol.

[blood]

Ive stopped LO, i had been using it for 5 days, around 4 days, i became lethargic. and had a headache, which carried on day 4 and 5. Day 6 i decided to stop it , and the headache was gone. I do feel a bit better now, could it be that lithium was repairing something in my brain, because of the headache?

Maybe 5 mg/day is simply too much for you?

I've seen 1 mg/day proposed as a hypothetical RDA.

You could consider chipping the tablets into 4 pieces - taking just a quarter of a tablet a day. This would provide very roughly 1 mg/day Lithium (instead of 5 mg/ day)?

It only took 0.3 mg/day of lithium to slow down the progression of cognitive impairment in Alzheimer's patients.

How long does LO need to be in your system to detect positive benefits anyways?

And yes do u think only 1 mg is helpful? If so I might try a lower dose.

It's conceivable that lithium needs to be taken long term for any protective benefits to become evident (at least with respect to cognitive decline). In one study that lasted only 10 weeks, lithium supplementation didn't have any effect on cognitive performance in Alzheimer's patients; in another study, lithium supplementation taken for 12 months did seem to produce some improvements in cognitive performance in people with an Alzheimer's diagnosis. Both of these studies were using high doses of lithium that would require a Doctor's supervision and careful monitoring of serum lithium levels.

It seems possible that even small doses of lithium might provide some benefits. E.g., an exciting newish study found that just 0.3 mg (3oo mcg) of lithium taken for a long period seemed to halt the progression of cognitive impairment (but didn't reverse it) in folks with an Alzheimer's diagnosis.

I haven't really noticed any benefits from low dose lithium that I can put my finger on. I see low dose lithium supplementation as a way of avoiding lithium malnutrition, and maybe a way of reducing the chances that I eventually become demented... what kind of benefits were you hoping for?

J Clin Psychiatry. 2009 Jun;70(6):922-31.
Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study.

Hampel H, Ewers M, Bürger K, Annas P, Mörtberg A, Bogstedt A, Frölich L, Schröder J, Schönknecht P, Riepe MW, Kraft I, Gasser T, Leyhe T, Möller HJ, Kurz A,Basun H.

Author information


Abstract


OBJECTIVE:

Lithium, a first-line drug for the treatment of bipolar depression, has recently been shown to regulate glycogen synthase kinase-3 (GSK-3), a kinase that is involved in the phosphorylation of the tau protein. Since hyperphosphorylation of tau is a core pathological feature in Alzheimer's disease, lithium-induced inhibition of GSK-3 activity may have therapeutic effects in Alzheimer's disease. In the current study, we tested the effect of short-term lithium treatment in patients with Alzheimer's disease.
METHOD:

A total of 71 patients with mild Alzheimer's disease (Mini-Mental State Examination score > or = 21 and < or = 26) were successfully randomly assigned to placebo (N = 38) or lithium treatment (N = 33) at 6 academic expert memory clinics. The 10-week treatment included a 6-week titration phase to reach the target serum level of lithium (0.5-0.8 mmol/L). The primary outcome measures were cerebrospinal fluid (CSF) levels of phosphorylated tau (p-tau) and GSK-3 activity in lymphocytes. Secondary outcome measures were CSF concentration of total tau and beta-amyloid(1-42) (Abeta(1-42)), plasma levels of Abeta(1-42), Alzheimer's Disease Assessment Scale (ADAS)-Cognitive summary scores, MMSE, and Neuropsychiatric Inventory (NPI). Patients were enrolled in the study from November 2004 to July 2005.
RESULTS:

No treatment effect on GSK-3 activity or CSF-based biomarker concentrations (P > .05) was observed. Lithium treatment did not lead to change in global cognitive performance as measured by the ADAS-Cog subscale (P = .11) or in depressive symptoms.
CONCLUSIONS:

The current results do not support the notion that lithium treatment may lead to reduced hyperphosphorylation of tau protein after a short 10-week treatment in the Alzheimer's disease target population.
TRIAL REGISTRATION:

(Controlled-Trials.com) Identifier: ISRCTN72046462.
Copyright 2009 Physicians Postgraduate Press, Inc.

Br J Psychiatry. 2011 May;198(5):351-6. doi: 10.1192/bjp.bp.110.080044.
Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial.

Forlenza OV, Diniz BS, Radanovic M, Santos FS, Talib LL, Gattaz WF.

Author information


Abstract


BACKGROUND:

Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer's disease, although no benefits were obtained from short-term treatment.
AIMS:

To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI).
METHOD:

Forty-five participants with aMCI were randomised to receive lithium (0.25-0.5 mmol/l) (n = 24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (Aβ(42)), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392.
RESULTS:

Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P = 0.03) and better perform-ance on the cognitive subscale of the Alzheimer's Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%.
CONCLUSIONS:

The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.

Edited by blood, 19 December 2013 - 03:22 AM.

[normalizing]

to answer that guy's question of headaches being related to anything being in repaired in the brain, NO. headaches are very natural normal sign OF SOMETHING WRONG. never has anything good caused headaches, why the thell would you assume otherwise ?

and blood, since you are like the expert here so far, isnt lithium carbonate naturally present in water and not lithium orothate ?

[blood]

New "micro dose" lithium supplement from Pure Encapsulations:

http://www.pureencap...dose-30-ml.html

(500 mcg lithium, as lithium citrate, per 1 ml serving)

[normalizing]

i wonder if lithium would help with your autism blood, because you cant converse with people properly at all

[blood]

i wonder if lithium would help with your autism blood, because you cant converse with people properly at all

In answer to your earlier question, I am not even remotely an expert on lithium, and I don't know what forms of lithium occur naturally in municipal/ mineral waters.

Edited by blood, 05 January 2014 - 02:05 AM.

[niner]

and what is the lithium form found naturally in water ?

If it's dissolved, then it's Li+, floating in water. There are negative ions in the water as well, although they may or may not have been the counterion of the lithium before it dissolved. Typical negative ions found naturally in water are sulfate, carbonate, and probably some chloride. When you take a molecule as a drug, then the rate of dissolution becomes an issue, as well as the ultimate solubility. With mineral waters or other natural sources, the lithium is already dissolved. If you want low dose lithium, then any form with decent solubility should be fine. There aren't that many options for reasonably priced supplemental lithium. 5mg orotate seems to have cornered the market. I wish I could find a low cost 1 mg pill in any soluble form, because I'm tired of having to split the 5mg tabs.

[Blankspace]

I wish I could find a low cost 1 mg pill in any soluble form, because I'm tired of having to split the 5mg tabs.

I'm not sure if this would be a better option for you, but this product has only 2.15mg per tablet, and splits very easily without any crumbling:
http://www.swansonvi...artate-100-tabs

 

Please note that the manufacturer has changed this product.

Edited by cryonicsculture, 11 June 2014 - 04:42 PM.

[blood]

Annoyingly, Drs Best has discontinued their lithium orotate product:
http://www.longecity...ithium-orotate/

[normalizing]

i have noticed others have too. local place had some forms, now none claims its RX only. lol is this some conspiracy to keep lithium out of easy reach from the public ?

[dudmuck]

And nary a peep about lithium on examine.com

[Strelok]

And nary a peep about lithium on examine.com

 

I emailed them and they said it was prescription only.  I emailed back that there were the lose-dose supplemental versions of orotate and aspartate.  They said that was interesting, and that they'd look into it. 

[aribadabar]

Swanson's lithium ororate product is also no longer available.

I saw it available as recently as early this month.

 

A sign of times?

[blood]

Swanson's lithium ororate product is also no longer available.

 
Thankfully, they are still selling lithium aspartate (which is a better value, & which I prefer):
http://www.swansonvi...e-5-mg-100-caps
 
If they kill this product, I will be disgusted. 
 

A sign of the times?

It's odd/annoying timing. Just as evidence for a beneficial effect from microdose lithium accumulates, it becomes more difficult to procure.

Edited by blood, 30 October 2014 - 09:47 AM.

[tunt01]

In regard to water solubility, which forms (excluding orotic acid/orotate) of lithium are the most water soluble?  I was also doing the micro (1 mg) dose at one point and found it to be so irritating that I gave up splitting the pills.

 

However, I would like to put say 5-7 mg in a bottle of water in my refrigerator and drink it throughout the week.  Anyone have any thoughts on this approach?

[blood]

However, I would like to put say 5-7 mg in a bottle of water in my refrigerator and drink it throughout the week.  Anyone have any thoughts on this approach?

Swanson's lithium aspartate caps can be emptied into e.g., orange juice. There is a little bit of 'grit' from the excipients (silica, etc) though.

I take 5 mg/day as I can't be bothered splitting caps or tabs.

I should mention that Relentless Improvement have introduced a lithium orotate product, at a very reasonable price point. (They make high quality products, and are also a Longevity sponsor and should of course be supported):

Relentless Improvement - Lithium orotate, 5 mg lithium/tab, 200 tabs

Edited by blood, 02 November 2014 - 11:06 AM.

[tunt01]

I've been reading a bit more about lithium and kidneys (AKI, kidney disease, etc).  I am trying to understand the molecular signaling which underlies some of these pathways.

 

 

cells that do not receive Wnt signals, glycogen synthase kinase (GSK) is presumed to phosphorylate β-catenin, thus marking the latter for proteasomal degradation. Wnt signaling inhibits GSK3 activity.

 SOURCE

 

 

Lithium also inhibits GSK3.  It is also established that klotho (which has been shown to be beneficial in the recovery of AKI) blocks the canonical Wnt-B/Catenin pathway.  

 

Loss of Klotho was closely associated with increased β-catenin in the diseased kidneys, suggesting an inverse correlation between Klotho and canonical Wnt signaling. In vitro, both full-length and secreted Klotho bound to multiple Wnts, including Wnt1, Wnt4, and Wnt7a. Klotho repressed gene transcription induced by Wnt but not by active β-catenin. Furthermore, Klotho blocked Wnt-triggered activation and nuclear translocation of β-catenin, as well as the expression of its target genes in tubular epithelial cells. Investigating potential mediators of Klotho loss in CKD, we found that TGF-β1 suppressed Klotho expression and concomitantly activated β-catenin; conversely, overexpression of Klotho abolished fibrogenic effects of TGF-β1

 

 SOURCE

 

 

 

 

 

Question:

 

If increased Wnt signaling (in example of loss of Klotho) is contributing to fibrosis of the kidney, how is Lithium accomplishing a similar affect if it is inhibiting GSK3B and subsequently B-Catenin:   Is it because lithium is preventing the degradation of Beta-Catenin, which would otherwise be destroyed via GSK3B/proteasomal destructive pathways?  Then Beta-Catenin is ultimately translocating to the nucleus?  

 

Is there a reason why a single dose exposure of lithium could be seen as beneficial post AKI could be seen as beneficial?  Would it make sense to cycle lithium 24 hrs and 24 hrs off (take it every other day)?

 

Sorry if this is basic, I'm trying to understand this better (how to compare the Lithium vs. TGF-B1/Klotho/Wnt etc. situations).  

 

 

Edited by prophets, 06 November 2014 - 03:13 AM.