Lithium Orotate

(updated 6/2016)

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.

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 it used doses of lithium orotate that were  roughly equivalent to the full adult human dose (e.g. 1500 mg in a larger adult).

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 in the first Brazilian study above (blood level 0.2 – 0.4), is far higher than what you find in some orotate forms on the internet. See my comparison table below.  To get a blood level of 0.2 would generally require about 150-300 mg per day of lithium carbonate, the usual prescription form,  depending on your kidney function.

The single 1979 study, and the lack of further such research since then, leaves open the question of safety of lithium orotate in human kidneys. Is it more or less risky than lithium carbonate?  This is a complete unknown.

Lithium in the water supply?

This story 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.  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. Kabacs )

Here are the data from the Japanese study, which is the most 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.

See the trend down and to the right? The higher the lithium level, the lower the suicide rate.

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.

Microdosing: how much actual lithium in each form?

Here are some numbers from a source I trust, Dr. Ghaemi’s newsletter (April 2016 issue).

Type dose elemental lithium equivalent in lithium carbonate
Average dietary intake 1 mg/day
Very high diet/water intake 5 mg/day 25 mg
lithium carbonate 300 mg 56 mg
lithium carbonate 150 mg 28 mg
lithium carbonate 25 mg 5 mg
lithium citrate 60 mg/ 1 ml 10 mg/ 1 ml 50 mg
lithium orotate 120 mg 5 mg 25 mg

In other words, to get the amount found in areas with very high water levels, one could use:

  • One pill of lithium orotate (120 mg/pill)
  • 1/2 of a ml of lithium citrate (at 60 mg/ml)
  • 1 ml of that same lithium citrate every other day
  • 1/2 of a 150 mg lithium carbonate every other day

Or one could just take a 150 mg lithium carbonate pill daily and be taking 4 times the amount that people are getting who live in areas with a lot of lithium in their water.  That’s what I have prescribed for patients (just a few so far) who are facing a high risk of Alzheimer’s .

Happily, I’m not alone in this. In a subsequent article in his newsletter, Dr. Ghaemi says “it is reasonable” to suggest 5 mg of elemental lithium for prevention of Alzheimer’s.

Microdosing using lithium citrate

To avoid the whole question of the safety of the orotate approach, one could just use lithium citrate. It’s a prescription pharmaceutical, but also available over the internet without a prescription.

But look at how little lithium is in the internet form! First, notice in the table above, the standard version of prescription lithium citrate is 60 mg/ml.  Compare one internet lithium citrate with 500 mcg per 1 ml.  That’s micrograms per ml, got that?  That means you’d have to take 2 ml  to get to just 1 mg per day.  Wow, there’s hardly any lithium in there.  To get to 5 mg a day, as in the table above, you’d need 10 ml per day. The whole bottle would be gone in three days!  (There are 30 ml per fluid ounce. You get 1 fluid ounce for $21.50).

So don’t bother with that route. Someone’s just making money there. Unless you believe in homeopathic doses, in which case I’m surely just offending you left and right on this website. Sorry, my religion is science, I’ll confess that.

How about lithium aspartate instead?

Another low-dose lithium route is lithium aspartate.  But whereas orotate is marketed for its special ability to deliver lithium,  aspartate is not regarded as special.  It’s just another ion to carry lithium, like the carbonate ion in regular prescription lithium.

Lithium aspartate can also be purchased over the internet. But what about the safety of aspartate, which after leaving lithium, will be floating around loose in your body? By comparison, when carbonate goes off loose, it joins a huge pool of carbonate already present in the body (carbonate is closely related to CO2, which we breathe out all the time).

In 20 minutes of looking, I could not find much about aspartate as a loose ion. In the small amounts that you’d get from lithium aspartate, it might be the same “drop in the bucket” as with carbonate, because it’s an amino acid, we eat it in protein all the time.

But cysteine is an amino acid also, and it quite clearly has effects on mood and anxiety (read about n-acetylcysteine, the more absorbable form).  So again, just like the orotate approach, once you leave prescription lithium carbonate, with which we have nearly 50 years of experience, we’re in unexplored territory, as best I can tell.

Yes, there are other products out there like potassium aspartate. But I did not come up with known, tested, routinely used medications that use aspartate (I could be missing them, there could be many I don’t know about).

For now, I think perhaps the safest route is to use low-dose prescription lithium in the hands of someone who knows what they’re doing with it. But I know that’s easy to say, while accessing such a person, and paying for it, is perhaps not easy at all, for many people.

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 ups into the 300 milligram range, she definitely needs thyroid testing.

Safety of high-dose orotate                                                           

A high-dose lithium orotate pill (e.g. 120 mg per pill; many contain far less) has 5 times less than less lithium in it than the lowest dose of  prescription lithium (carbonate).   You’d have to take a lot of orotate to get much lithium. An overdose of lithium orotate produced a sub-therapeutic blood level. Pauze’  However, safety of lithium depends on your kidney function. If that was poor, even the amount of lithium in the internet orotate forms could be dangerous.

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 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.