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 Lithium Orotate 
(revised 10/2014)

Summary

  1. Lithium orotate might be a good idea, especially for some people.
  2. It may have some risks too. We don't really know. (Those who claim low risk, they don't know either).
  3. You may be willing to pay for it, and maybe even take some risk. Do you want to be out front, on this curve? For some people, that may be a risk worth taking.

[Bullets below indicate the various sections of this essay. Automatic links to these headings below await website rebuild, 10/2014]

Who might consider orotate?

There are now at least three groups of people interested in lithium orotate.

  1. First, there are people for whom the idea of "lithium", as a drug from a psychiatrist, is a frightening prospect. And that's quite understandable: kidney risk, thyroid risk, risk of side effects, risk of "toxicity" if the blood level gets too high, risk for about 1 person in ten who gets so flat and dull and blah they hate it (and some then write about this experience on the 'net). Yeesh, who'd want to take that. Not to mention the reputation: "lithium, that's for people they hospitalize, serious mental illness", etc.But for many of these people, an ultra-low-dose approach that avoids all these problems, and that might address their mood problems (and maybe more, depending on who you read), now that's worth looking into.
  1. Secondly, there are people who have heard of the research regarding lowering the risk of cognitive decline toward Alzheimer's. If you had a parent with Alzheimer's, wouldn't you be interested in some ultra-low-dose, "water supply" level step you could take to lower your risk? After all, even if the evidence for this effect was extremely slim, if this version of lithium was really cheap and carried no risk, why not just take it in the hopes that further research would continue to show potential benefit? Some people whose parents became ill early, or who already see some sign of memory decline, may feel they don't have time to wait for the further research.
     
  2. Finally, a few people might consider taking lithium orotate because tiny amounts of lithium in a city's water supply have been correlated with lower suicide rates in those cities.  In one study, the higher the lithium in the water, the lower is the suicide rate, with few exceptions.

The key for all these groups is to find a dose that is so low it's almost impossible for it to cause any harm.  But tiny-dose lithium has been marketed as a vitamin, and has created a very significant market, full of outrageous claims.  Until now I've just dismissed lithium orotate entirely because of those claims.

Let's Calm Down

Okay, first let's all calm down (including me) and not judge lithium orotate as necessarily good just because it doesn't seem to require a prescription; nor necessarily bad because people are selling it on the internet. I'll even try to hold off on judgment about how we may be losing a scientific mindset when we leap to this kind of thing without a randomized trial versus placebo.

And from that calm place let me acknowledge that lithium orotate could be a good idea, especially for some people. And that, at the same time, we really don't know. Remember, stuff like this routinely gets a 25-30% response rate, meaning people do indeed get better when they take it, because that's the placebo response rate in mood and anxiety disorders studies.

Data: One Study (Two?) So Far

Okay, let's look at the data. The one relevant paper, in my view, is not the Dr. Nieper stuff you read about (here's a rather thorough review). Instead there's the small trial from Brazil in patients with Minimal Cognitive Impairment, MCI. The daily dose was only 300 micrograms. Yet in a year, it worked to prevent progression toward Alzhiemer's. Wow, that dose is even less you get from lithium orotate as sold on the internet – a lot less.

If you're being a good scientist you'd want a second study, by another research group, also seeing the same positive results.  But that means waiting another year. Oh wait, there is a second study. It had a smaller group of subjects, though, and perhaps for that reason, even though the results went in the same direction as the first study, it wasn't “statistically significant” (meaning, roughly, it could easily have happened by chance).  Interestingly, this second study used a much larger dose, but not “bipolar” doses:

  dose blood level (mmol/L)
First Brazilian study 300 micrograms not tested (too low!)
Second Brazilian study about 300 milligrams 0.2- 0.4
Routine bipolar treatment 900 – 1500 mg 0.7-1.1

 

What to do with these two Brazilian studies?  Different doses. Different outcomes. The second is not a replication of the first, and the first one used an unprecedented low dose.

Here's a technical review of all this by the authors of the second study, if you wish.Forlenza  Note they conclude by asking: "so, are we ready to start using lithium to prevent Alzheimer's?" and conclude no. Because they are going by scientific and standard medical criteria for judging a therapy. But what if you are facing Alzheimer's? Might you consider a different standard? One that compares risks, as well as what's known about effectiveness?

Safety of low-dose orotate

Lithium orotate has received only minimal evaluation in terms of its safety. One 1979 study in rats found it more harmful than the conventional form (lithium carbonate) to the animals’ kidneys.Smith  That study seems to have brought an end to scientific study of the orotate approach.

But was it a fair evaluation?  Do the math, a reader says: “the authors cite a dose of 2 mmol/kg of Li. That translates to 14 mg/kg, or >750 mg for a small adult!”  Thank you, Peter.  In testing lithium orotate, the investigators selected a dose roughly equivalent to the full adult human dose (e.g. 1500 mg in a larger adult).

Thus the doses that are sold on the internet, which are far below those used in bipolar treatment, have not been tested for their safety. Even the low-dose lithium tested for prevention of Alzheimer’s, described above (blood level 0.2 – 0.4), is higher than what you find on the internet, which is often as low as 5 mg per pill. By comparison, to get a blood level of 0.2 would generally require about 150-300 mg per day of lithium carbonate, depending on your kidney function.

The single 1979 study leaves open the question of safety of lithium orotate in human kidneys. Is it more or less risky than lithium carbonate, the version in prescription pills?   This is a complete unknown.

Lithium in the water supply?

You've probably heard this one. It even made the New York Times, in an article by a psychiatrist.Fels  Lithium is found in the water supply of several cities around the world, at up to 170 mcg/L.  Amazingly, those cities have lower suicide rates than nearby cities with little or no lithium in their water.  (One study did not find this relationship but. there wasn't as much lithium in the water there; 21 mcg/L or less.Kabacs )

Here are the data from the Japanese study, pretty striking:

Each circle is a separate city, of varying sizes. The logarithmic scale means that a very large range of lithium levels in the water supply is being displayed here.
Each circle is a separate city, of varying sizes. The logarithmic scale means that a very large range of lithium levels in the water supply is being displayed here.

Don't worry:  putting lithium in everyone's water is extremely unlikely. You should have seen the fuss that arose in the community next door to mine over putting fluoride in the city water to prevent tooth decay.  It took a couple of doctors campaigning to get it back in after the City Council took it out.GT  And that was just teeth.  Putting something in there to mess with your head ? Forget it.  But with lithium orotate, people could do this on their own. Not that I'd recommend it at this point (see Conclusion below) but it's possible.

Thyroid

Hold on a minute, though. Microdose lithium may not pose much risk to kidneys. But lithium commonly causes thyroid problems (usually getting too low, "hypothyroid"; rarely getting too high, "hyperthyroid"). One person in 10 develops this problem at standard bipolar-treatment doses. And it’s far more common in women than in men, which means the risk for women is even higher, more like one woman in 5, or even one in 3.

So, what would lithium orotate do to your thyroid state? As far as I know, this too has never been studied (despite all the lithium orotate flying around out there). Maybe 300 micrograms poses very low risk (recall that was the dose in the microdose Brazilian study); but once someone get up into the 300 milligram range, she definitely needs thyroid testing.

Safety of high-dose orotate                                                            
One of the orotate versions I found in looking around just now is 120 mg per pill. This approaches the 150 mg dose of lithium carbonate I use when I’m “tiptoe-ing”.  In older folks especially, it would not be safe to use 120 mg of lithium regardless of form without knowing how your kidneys and thyroid are working. I’m surprised the doses have gotten that high (a few years ago they were far lower. Looks like the companies are competing with one another and in the process they’re approaching doses that now present some risk). 

But even a higher-dose lithium orotate pill contains less than one-third the dose of a low-dose prescription lithium (carbonate), as shown in the table below.  Values here were extracted from calculations by Professor Peter Gray at Central Washington University.

Form of lithium amount per pill or glass units per day mg of  lithium
lithium carbonate 150 mg 1 14 mg
lithium citrate (liquid) 150 mg 1 15 mg
lithium orotate high dose 120 mg 1 5 mg
lithium orotate low dose 5 mg 1 0.2 mg
Texas groundwater high 70 mcg/L 8 8-oz glasses 0.3 mg
Texas groundwater low 170 mcg/L 8 8-oz glasses 0.1 mg

Conclusion

For my patients with MCI (minimal cognitive impairment), I’m checking their kidney function and in several cases prescribing lithium. This is based on the two Brazilian studies. And it’s based on the basic science behind these trials, which is substantial and also suggests this approach ought to help. And because very-low-dose lithium is easier to keep use safely than full-dose lithium.

Could someone just start taking lithium orotate for the same reasons? I can see why someone would be tempted: get lithium’s potential brain benefits, no doctors, no blood tests. How big a dose can one take safely in this fashion? Unknown. Is it safer to use lithium carbonate, say 150 mg, the lowest available prescription dose, than to mess with orotate, which is so untested? I think maybe so:  at least that way you can get your kidney and your thyroid checked too.

Lastly, does it accomplish anything to take tiny-dose lithium, like they used in the first Brazilian study?  Now there’s something I’d love to know, and when someone repeats that study, if they get the same result, I’d think nearly everyone would want a 300 mcg pill. Or come to Ashland, Oregon and have a sip from the public fountain once a day.

 

 

 

____

 

the page below was written 9 months ago and warranted revision. I'm keeping the old one here for a short while longer in case you came back looking for it. 

(started 1/2014; co-written by MS3 Sarah Bobnick) 

Summary: 

1.       Low-dose lithium, and ultra-low-dose lithium, can have tremendous value for some people. 

2.       The limited research available suggests that lithium orotate could be riskier to kidneys than regular lithium.

3.       The idea that lithium, given as the orotate version, reaches the brain better than regular lithium, has not been clearly demonstrated.

4.       Therefore there is no clear reason to use lithium orotate.  It has no clear evidence for superiority over regular lithium, and might have more risk.  The only reason it continues to get any attention at all is because of the marketing efforts of those who profit from it.

More below:


What is lithium orotate?

The regular form of lithium, available by prescription, is lithium carbonate. This is plain old lithium, combined with carbonate to make a solid. It can also be combined with orotate to make a solid.

Once there was a claim that the orotate version delivered lithium to the brain more effectively. And therefore it could be given at much lower doses than regular lithium, yet still provide benefit.  Research in support of this claim is very old and very limited.

Lithium orotate is marketed as a dietary supplement and so does not require regulation by the Food and Drug Administration.  Because it is not regulated, those who sell it can make claims about its benefits without much restriction.  Let the Buyer Beware!

Benefits of low-dose lithium

Full-dose lithium can cause side effects such as tremor, and diarrhea.  If people get those side effects, they often want to stop taking it (they actually ought to start by talking to their doc� and then turning it down a little bit). These and other high-dose effects have given lithium a bad reputation.  But low-dose lithium can still provide numerous benefits:   

1. Antidepressant add-on

Lithium can add to the antidepressant effects of other treatments (e.g. exercise, psychotherapy, light therapy, or antidepressant medications).Bschor 

2. Anti-anxiety effects

Lithium, even at low doses, can help people pull out of mixed states (combination of depression and agitation/anxiety/irritability and/or sleep disturbance). 

3. Possible anti-Alzheimer�s effect?

Multiple recent studies are suggesting that for someone who is likely to develop Alzheimer's disease, very-low-dose-lithium might slow their progress toward that currently-untreatable disease. In addition to several lines of research which support this idea, there has even been a specific trial testing lithium in this role. Forty-five patients with early signs of possible Alzheimer's disease were randomized to either lithium or placebo. Those who received lithium showed significantly less worsening of their cognitive abilities (almost none) compared to those who received placebo, over the following year.Forlenza 

Evidence for risk from lithium orotate

In 1979, one of the world's most respected lithium researchers , Mogens Schou, studied the lithium orotate approach and found (in rats) that it seemed to produce more kidney damage than regular lithium. That was the last time lithium orotate was studied in a rigorous way.

(One woman did manage to get lithium toxicity from lithium orotate, but that was after ingesting 18 pills at once. Pauze At least this shows that some lithium orotate pills from the internet really do contain a significant amount of lithium. )

Why is lithium orotate even considered ? By anyone?

I think there are 2 reasons for this.

1.  Is it better than lithium carbonate?

A glimmer of evidence, from 2 studies in the 1970s, suggested lithium orotate might deliver lithium to the brain better than regular lithium (lithium carbonate). 

The first, the one that started all this, was by Hans Neiper (no abstract online for is 1973 paper; a summary by a psychologist is in here).  Nieper made broad claims for the benefits of low-dose lithium (many of which I agree with) but attributed them to the orotate approach.  He thought the orotate allowed lithium to reach and stay in the brain better than lithium carbonate.  One study agreed. Kling  One study did not. Smith

Why hasn�t it been studied more? Some might say this is because Western medicine is only interested in making money and that by around this time, there was little money to be made with pharmaceutical lithium.  However, in my opinion, if that was an accurate explanation, we would not see the remarkable number of studies that have been produced recently on fish oil or N-acetylcysteine, which also are not money-makers for Pharma.   JP link those pages

Instead, I think the research came to a halt because of Dr. Schou�s findings noted above. JP link Unfortunately, that was only a single study, in rats. But it was enough to put a dagger through further research on lithium orotate. As far as we know at this point, it might still be possible that lithium orotate is not really more dangerous, in humans, than lithium carbonate. One study in rats is not enough to really know. However, it does leave the burden of proof upon those who would promote lithium orotate to demonstrate its safety. Unfortunately, doing that right would take a lot of money. I think that is why we are stuck.

2.  Follow the money (once again)

The other reason there is so much noise on the Internet about lithium orotate is because of all of the marketing that it receives from companies which are profiting from selling it. I hope that you, gentle reader, have learned not to trust those who are making money on something to give you accurate information about it.

(How much of this stuff have I actually read?)
I have read the Smith paper (
online). I have not read Kneiper�s 1973 manuscript, instead relying on the online summary by the psychologist who does appear to have read it (here).  I have read abstracts only for all the other cited studies.

Why haven�t  I looked into this more? Studied the full articles, for example? Because at this point the whole issue is stuck, as described above, on the one study that showed greater risk with orotate than with regular lithium. Even though it�s only one study, it was by a very reputable source.  Thus we now need further evidence showing safety, or  a lot more evidence for greater benefit from lithium orotate, before anyone should consider using the orotate form. Besides, for low-dose lithium, we can just use regular lithium carbonate, 150 mg, which bothers very few people. If someone made a smaller one, I would probably use it sometimes, but I don't really need it. (One can use a liquid lithium, lithium citrate, and make much smaller doses than 150 mg, but again, I don�t really need it so I very rarely use this approach).