(updated 4/2019)

Who might consider lithium orotate?

At least three groups of people are interested in lithium orotate.

1. “Lithium” sounds frightening, but there are reasons to consider taking it.

Fear is certainly understandable. Prescription lithium has some significant risks, not to mention stigma. There’s kidney risk, thyroid risk, risk of side effects, risk of “toxicity” if the blood level gets too high. There’s a chance prescription lithium will make you so flat and dull and blah you’d hate it (and maybe write about this experience on the ‘net). That happens to about 1 person in 10, in my experience (meaning it doesn’t happen at all to the other 9).

Then there’s the reputation: “lithium, that’s for people they hospitalize, serious mental illness”, etc. But low-dose lithium can potentially avoid all these problems, and might still address their mood problems. It’s really a different drug than full-dose prescription lithium.

2. Alzheimer’s dementia.

Some have heard of the research suggesting lithium might lower the risk of dementia. If you had a parent with Alzheimer’s, wouldn’t you be interested in some simple low-risk step you could take that might lower your chances of getting Alzheimer’s yourself? 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 pretty young, or who already see in themselves some sign of memory decline, may feel they don’t have time to wait for the further research.

3. Lowering suicide risk

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. A person might consider this if she/he/they have really struggled with thoughts about suicide and want some help contending with that stress.

The goal for each of these groups is to get lithium’s benefits without the risks and potential side effects, right? Okay, so let’s look at different ways you might do that. Oh, and many of you would like to do this without a doctor, for various reasons.

Well, it turns out that all three reasons above are based on research with lithium carbonate, the prescription stuff. But I’d love to show you some of those data. Then we can look at the lithium orotate approach.

Data: low-dose lithium (not lithium orotate)

Most of the research on lithium has been on its use in manic-depressive illness (now called Bipolar 1). That work has shown that pretty high blood levels are needed to prevent mania. Just a little higher and it’s pretty dangerous. Any lower and it doesn’t offer the needed protection. Almost everything you’ve read about lithium refers to the doses needed to get those high blood levels.

By comparison, doses for suicide prevention, possible dementia prevention, and possible mood benefit can be much lower. Tiny, by comparison. Low enough that even lithium orotate from a grocery store might get you there. But unfortunately we don’t have any research on lithium orotate in humans. So you have to figure that lithium is lithium once it reaches the brain, regardless of how it got in you. (Yes, there are Hans Kneiper’s observations but not deliberate study. He thought the orotate version might reach the brain better but that has not been studied either).

Low-dose lithium for mood

My data here are no better than Dr. Kneiper’s: just observations. I’ve seen very-low-dose lithium help a lot for complex mood problems. Sometimes the lowest prescription dose of lithium is enough to really help depression. So let’s talk doses now. We’ll be comparing 150 mg, the smallest made, versus 900 to 1500 mg per day.

For manic-depressive illness, to get sufficient blood levels takes those bigger doses. It varies a lot from person to person, so quite a few lab tests are often needed to make sure we know where the level is. Technically we’re shooting for somewhere between 0.7 and 1.1 (the units don’t matter here; it’s mmol/L or mEq/L if you care). By comparison, a dose of 150 mg per day will land most people with normal kidneys around 0.3 or less. I’ll talk later here about whether those people need a blood test at all.

“Low dose lithium”, in my hands, means a blood level of 0.6 or less. Not enough to prevent mania, for many people who have that risk (might be enough for some, that’s tricky to figure out). But 0.6 is quite far from the dangerous levels (1.3 and up). In my experience, low-dose lithium can really depression. Not every time, not even so often as to make it one of my first choices. But often enough that when an antidepressant alone for Major Depression hasn’t worked, adding low-dose lithium is a routine option. That’s in the big depression treatment guidelines, not just in my practice!

Low-dose lithium for suicide prevention

We don’t generally know if there’s any lithium in our drinking water. If there was a lot in yours, you wouldn’t need to consider this strategy. But since most places probably have little (more on that below)…

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. (A few studies did not find this relationship but in soeveral of those, there wasn’t as much lithium in the water. A smart fellow has listed/linked many of them. )

Here are the data from the Japanese study, which is the most striking. Each circle in the graph below is a separate city, of varying sizes. The scale means that a very large range of lithium levels in the water supply is being displayed here (it’s logarithmic; apologies for having lost units in translation) .

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.

Low-dose lithium for dementia prevention

Here we actually have some randomized trial data, the best kind. It is a small trial from Brazil in patients with just a hint of oncoming dementia, so called “Minimal Cognitive Impairment”, MCI. The daily lithium dose was only 300 micrograms. (That’s one thousandth of a small dose, e.g. 300 mg per day, that I was just talking about above). 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. Ah look, 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 the result could have happened by chance). Interestingly, this second study used a much larger dose, but not manic-depressive 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.

There’s a technical review of all this by the authors of the second study, if you wish. 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?

I think that when you look at low-dose lithium that way, it’s pretty obvious: why not? For people with good kidney function and high Alzheimer’s risk, I would not hesitate to prescribe 150 mg of lithium. I’d prescribe even less if there were such a pill available. Oh, that brings to mind lithium orotate, doesn’t it? Though not studied for Alzheimer’s prevention, it almost surely delivers a dose in the range of those used in these two Brazilian studies (I wish I knew for sure. But there are many different lithium orotate versions out there).

Wait, more studies have been published lately. Neither is a randomized trial like those described above. Both of them compare Alzheimer’s rates in areas with low versus higher levels of lithium in the water. The first examines the entire country of Denmark (!). But the rates vary only slightly and not “linearly”, meaning the rate of Alzheimer’s doesn’t go down the higher the lithium in the water: the rate kind of jumps around. The areas with the highest amount of lithium did have the lowest Alzheimer’s rates, but overall this study does not really push us one way or the other.

The second study looks at the state of Texas (15 times larger than Denmark). Yes, the researchers found that higher amounts of lithium in the water were associated with lower Alzheimer’s rates. But in a follow-up paper, the same research group shows that urban areas have more lithium in their water supplies than rural areas. In Texas, rural areas have lower rates of education, higher rates of diabetes, and other factors that might explain the entire difference in Alzheimer’s rates.

The same alternative explanation — other factors, not lithium, might explain what looks like a lithium effect — was thought most likely in the latest study. The authors think that water-level lithium represents too small a dose to do anything. But there are just too many studies to ignore now, suggesting a microdose lithium effect (when consumed presumably for years). For example, here’s another one: in Japan, the higher the lithium in the water, the lower the rate of psychotic symptoms in young people. (My response to the skeptical authors).

How much lithium in your water ?

This varies a lot. In the Texas study above, the high-lithium areas averaged 63 micrograms per liter of water. That’s really high. The low-lithium areas in Texas averaged about half that, 33 micrograms per liter. But compare Denmark: the high-lithium areas max’d out at 27! And their low-lithium areas were in the range of 2-5 micrograms per liter.

The United States Geological Survey has drilled wells all over the country and tested the water for many things, including lithium. The Director of that program kindly helped me access their results. If you really want to know, you’ll find lithium levels by state and county in a table ( US groundwater lithium) she helped me assemble. It’s not too hard to read: find your state and then your county. Sorry, only a few wells per state! ( If you want more details, here are the acquifer data USGS lithium sort by state, and here is that list sorted by highest concentration to lowest USGS lithium sort by level.

If you don’t want to or can’t mess with that table, here’s the general idea. Lithium levels in U.S. water supplies vary, a lot. Here are a few examples, but careful: a county right next door could have a far different amount. Don’t look at your state and assume that’s in your water, unless you leave in that county (even then there’s probably still a lot of variability, unless you’re in the middle of the acquifer).

Examples (lithium in micrograms per liter, the standard unit for groundwater levels):

IOWA TAMA 649.7 TEXAS RANDALL 576.0 NEW MEXICO SANDOVAL 480.7 WYOMING WASHAKIE 471.5 ILLINOIS PEORIA 392.8 ARIZONA MARICOPA 380.0 WYOMING FREMONT 355.8 NEVADA WASHOE 225.1 IOWA POLK 222.2 COLORADO ADAMS 137.3 UTAH SALT LAKE 137.3 NEW YORK SARATOGA 98.7 WISCONSIN PIERCE 91.3 MARYLAND QUEEN ANNE’S 61.9 IDAHO MINIDOKA 48.1 CONNECTICUT HARTFORD 48.0 KANSAS THOMAS 47.9 VIRGINIA DINWIDDIE 47.8 SOUTH CAROLINA BERKELEY 33.2 UTAH SALT LAKE 29.4 KANSAS SEDGWICK 28.1 MINNESOTA MAHNOMEN 25.0 FLORIDA INDIAN RIVER 20.7

After that in the USGS tables above come almost 3,000 samples with less lithium in the water than in these examples. Remember, it varies a lot (it’s the acquifer that matters!). But in general, the vast majority of water supplies in the U.S. have very little lithium in them.

Can you get test kit to measure lithium in your own tap water? Not that I think this is really important, mind you. But I’ll bet you’re wondering, if the data above have not satisfied your curiosity. So I surfed a while and found no such kits. If you find one, let me know; again, because people are going to be askin’…

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 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.

Microdosing: how much actual lithium in each form?

Here are some numbers from a source I trust, brilliant psychiatrist Nassir 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, you’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: accessing such a person, and paying for it, is 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, the prescriptions I routinely use, they definitely need thyroid testing.

Safety of high-dose lithium 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 and thyroid 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.