Lithium as a neuroprotective agent

[ahmo]

I don't understand the science, but note that Lithium is a good thing.

http://www.brainmysteries.com/research/Neuroprotective_effects_of_low_concentration_of_lithium.asp

Lithium, as a neuroprotective agent, benefits for neuronal survival. Recent cDNA array studies have demonstrated that mood stabilizer lithium exhibits neuroprotective effects through multiple targets. Dr. Riadh Nciri and his team, Purpan Medicine Faculty, Paul Sabatier University, France, exposed SH-SY5Y cells to 0.5 mmol/L lithium carbonate for 25-50 weeks and then detected the expression levels of some neurobiology related genes and post-translational modifications of stress proteins in SH-SY5Y cells. cDNA arrays showed that pyruvate kinase 2 (PKM2) and calmodulin 3 expression levels were significantly down-regulated, phosphatase protein PP2A expression was lightly down-regulated, and casein kinase II, threonine/tyrosine phosphatase 7, and dopamine beta-hydroxylase expression levels were significantly up-regulated. Besides, western blot analysis of stress proteins (HSP27, HSP70, GRP78 and GRP94) showed an over-expression of two proteins: a 105 kDa protein which is a hyper-phosphorylated isoform of GRP94, and a 108 kDa protein which is a phosphorylated tetramer of HSP27. These results suggest that the neuroprotective effects of lithium are likely related to gene expressions and post-translational modification of proteins cited above. This paper was published in Neural Regeneration Research (Vol. 9, No. 7, 2014).

Note: This story has been adapted from a news release issued by the Neural Regeneration Research

 

[Misfit Toy]

Lithium the medicine is harsh, but Lithium Oratate got me through a tough time years ago. It doesn't work for me now, but it helped with anxiety and had anti-viral properties from what I remember my doc telling me. This supplement is also mild and great for anxiety.

 

[ahmo]

Yes, I've been using 2.5-5 mg Li Orotate AM/PM. Really helped w/ my mood swings.

 

[anciendaze]

Since various forms of lithium salts are widely available, I think it appropriate to remind people that the positive effects as a mood stabilizer take place at concentrations which come within a factor of two of toxic reactions. You can't safely take lithium without regular blood tests because your ability to tolerate the drug varies with physical condition. One of the symptoms of an overdose is "leaden fatigue", which leads to confusion about whether to increase or decrease dose. There are other symptoms which may put you in a drunk tank when you need emergency care.

Long ago, the use of lithium salts as a dietary substitute for salts of sodium was stopped after a number of people died when it caused their hearts to stop. There have been other fatal reactions, and removing lithium rapidly may require dialysis, which is not a great experience.

Just a reminder that no drug is entirely "a good thing".

On the positive side, in addition to the claimed "neuroprotective" effects, we also have evidence in the case of AIDS that lithium may itself lower viral titers. Exactly how it acts as an antiviral agent is unknown. Several drugs labeled as antivirals, and some antibiotics, also exhibit neuroprotective effects. It is possible they are acting against viral infections or active HERVs which are being overlooked because the viruses in question are endemic and considered harmless. We simply don't know.

It is always a good idea to be cautious when you enter territory where experts are uncertain.

 

[Insomniac]

My gut could not tolerate Lithium orotate, it does not tolerate many supplments.
I have been trying Lithia water supplement instead (Lithium Chloride)
http://www.evitamins.com/Lithia-Water-Natural-Heritage-Products-51438

So far I feel no difference so I wonder if there is anything in the water.

 

[Little Bluestem]

@anciendaze, or anyone else who knows, is lithium orotate a lithium salt?

 

[anciendaze]

@Little Bluestem,

It wouldn't be called lithium orotate if it were not. The arguments are over the amounts of free lithium ions which reach the brain. Here's the Wikipedia page. The problem with taking this as a mood stabilizer, etc. is that it appears the action is still dependent on the concentration of lithium ions in the brain, which are subject to the cautions I stated above. Low concentrations are generally ineffective, while those within a factor of two of toxic levels need regular monitoring. Please note that serious adverse reactions have been reported, just as with more common lithium salts.

This monitoring is not just a one-time test. If anything impairs renal (kidney) function, the concentration of lithium ions can shoot up. Because ME/CFS patients often have a disregulated HPA axis, which also controls excretion of ions like sodium, potassium and lithium via hormones like vasopressin, it is especially important to watch for changes. An intake of lithium you can tolerate when you have polyuria may be too high if other factors slow excretion. Something as simple as going off caffeine can make a difference.

 

[L'engle]

I have to say personally it has had lasting side effects even at a small amount. I took a TOTAL of 25mg of lithium orotate (less than 5mg per day) over the course of a month and it inflammed my thyroid. As well parathyroid has been very oversensitive to vitamin d since taking it. I have lost so much sleep this year due to the vitamin d problem which I did not have prior to taking lithium orotate. This isn't minor and it hasn't gone away.

On the other hand it did improve my ability to use sodium and b12. I really don't know what to say about this supplement as I would still have a huge b12 problem without it but have a huge vitamin d problem with it.

So be warned. It can have terrible side effects. The TOTAL amount including all doses was only 5X5mg lithium orotate tablets. The side effects I'm experiencing are from this generally accepted dosage.

 

[whodathunkit]

@anciendaze: any idea why or how lithium causes the symptom of "leaden fatigue"? Is that the purported thyro-suppressive effect of lithium, or something else? Are you comfortable commenting on this?

@L'engle: FWIW, orotate is supposed to be much more bioavailable than other forms, which is one reason doctors can get away with such big honking doses of other forms of lithium.

I don't mean to sound unsympathetic...I'm really sorry you're having ongoing problems and I really love your avatar.

And I had a not-great experience with lithium myself at only 5mg of orotate per day. No lasting effects but I was very wary of it because I'd read some things. I tried it because I wanted to see if it would help with B12 uptake. I wasn't really on it long enough to know if it did or didn't, although if I had to say I'd say it probably did.

I'm just throwing that out there about dose mostly for other people. I've heard great things about lithium, but also bad things, and a lot of it seems to be very dose dependent. Starting very low and going very slow seems like the very best course of action for this nutrient.

 

[adreno]

Lithium increases grey matter in the brain, but that isn't necessarily a good thing. We probably are more in need of white matter than grey matter.

 

[anciendaze]

@anciendaze: any idea why or how lithium causes the symptom of "leaden fatigue"? Is that the purported thyro-suppressive effect of lithium, or something else? Are you comfortable commenting on this?
...

Not really. Even something as simple as an ion of an alkali metal like sodium, potassium or lithium can have powerful, non-linear effects. (I happen to know someone with serious problems in controlling potassium levels, though that extreme sensitivity is very rare. You can search for this kind of thing under the term channelopathies.)

When I say nonlinear, I mean that response is not proportional to dose, and that combinations of responses do not combine additively. What passes for plausible reasoning on these subjects is very likely to be wrong. Higher doses may even have the opposite effects from lower doses.

The original claim, as far as I understand it, was that lithium orotate did not release lithium ions the way something like lithium carbonate or citrate did because of covalent bonding. This turned out to be wrong.

The action of lithium has been investigated many times since it was discovered to be useful in controlling mania. It is connected with a number of fundamental biochemical processes, and not just in nerve cells. A very important effect outside the brain concerns cardiac function. I don't believe there is yet a research consensus on exactly how it works in those cases where it does work.

 

[L'engle]

@whodathunkit. Clarification: 25mg is the TOTAL lithium orotate I took over the course of the month adding up all doses. The largest single dose I had was the first one, 5mg, and after that I ramped down to less than 2mg per day. I edited my first post to make this more clear. . I feel it's important to know what can happen at even doses of less than 5mg. I am an outlier but people need to understand what can happen as a worst case.

 

[whodathunkit]

@L'engle: done. And I agree with you, we can't be swept away by glowing recommendations when it comes to lithium, but other minerals, too.

Like you, I think I'm an outlier with lithium because I took a very small amount for a very short time and didn't do well. But I've heard such great things about it that I'm still glad it's available for people to use on themselves instead of having to go through a doctor. I just wish I was one of the great anecdotes (as I'm sure you do, too) instead of an outlier.

I hope things get better for you!

 

[L'engle]

@whodathunkit. Sorry it didn't work out for you either. Thanks for the well wishes!

 

[npeden]

Yes, I've been using 2.5-5 mg Li Orotate AM/PM. Really helped w/ my mood swings.

I am looking for 2.5 mg. lithium orotate. I have COMT among many others but all I can find is lithium o. 5 mg. Yasko says to take a low dose and Wikipedia and other places say it harms the kidneys. But I really need it to help calm my excitability and though I don't notice anything on my one day's trial I want to try it for awhile. Any help is greatly appreciated.

 

[ahmo]

Orthomolecular Products from iherb makes 10mg caps. I open them and use partial caps.

 

[Bob]

I am looking for 2.5 mg. lithium orotate. I have COMT among many others but all I can find is lithium o. 5 mg. Yasko says to take a low dose and Wikipedia and other places say it harms the kidneys. But I really need it to help calm my excitability and though I don't notice anything on my one day's trial I want to try it for awhile. Any help is greatly appreciated.

Slightly off-topic, and perhaps it's already been discussed, but have you thought about trying beta-blockers for excitability?

 

[Little Bluestem]

Vitamin Research Products makes a 130 mg capsule of Lithium Orotate which provides 4.8 mg of elemental lithium. ½ capsule would be 2.4 mg.

 

[A.B.]

@anciendaze: any idea why or how lithium causes the symptom of "leaden fatigue"? Is that the purported thyro-suppressive effect of lithium, or something else? Are you comfortable commenting on this?

It's probably the thyroid suppressing effect. I experienced it first hand while experimenting with low dose lithium orotate. It produced a sudden drop in energy levels on the first day of taking it. I was expecting positive effects, and it took me a week to realize it was actually the lithium causing this.

On a side note, it seems that I react negatively to all medications which purportedly suppress thyroid function, while I react positively to all medications that purportedly increase it (too much will cause bad crashes though).

 

[stridor]

I've taken high dose lithium when I used to have Bipolar symptoms and take low dose now. My understanding is that part of the neuroprotective effects of this (and some other psych meds) comes from increasing glutathione.