Friday, February 25, 2011

Lithium and Longevity

A new paper was published this week - Low-dose lithium uptake promotes longevity in humans and metazoans.  Now, as a psychiatrist, I'm a lithium fan.  Apparently, it is an essential trace micronutrient (who knew) aside from the uses for decreasing suicide and helping mood stabilization. Want a primer - look at my blog post here.  (Here is the original lithium for treating mania paper by John Cade if you are interested.)

Decreasing suicide?  Yes, well lithium is actually very good at keeping people alive.  Even those with bipolar disorder or major depression who have no real symptomatic improvement seem to have less suicidal thoughts and suicides while on lithium.  Very interesting.  But why?

Let's start with some observational studies.  Back in 1989, Schrauzer and Shrestha published a paper called "Lithium in Drinking Water and the Incidences of Crimes, Suicides, and Arrests Related to Drug Addictions."  They took information about the lithium level in the water of  27 counties in the Great State of Texas.  Seems that counties with higher lithium levels in the water had a statistically significant decrease in the incidence of homicide, suicide, arrests for opiates and cocaine, and violent criminal behavior.  Now to put things into perspective, a high lithium water content translates to about 2mg of lithium a day.  Psychiatric doses start at 300mg daily. 

From the 1989 paper:

Lithium has previously been used to control episodic outbreaks of rage among prisoners and in the management of drug abusers.  Animal experiments have demonstrated that lithium suppresses cocaine-induced super sensitivity... the kindling phenomenon following the chronic application of ... a central nervous system stimulant, and head-twitching in response to the administration of mescaline.  Furthermore, lithium has been found to [improve] distractability... and produce improvement of selective attention to stimuli... it prevents behavioral alterations owing to social isolation, lowers aggressivity owing to confinement... and causes a normalization of spontaneous motor activity.

 Wow!  That's a lot for one little trace mineral.  And observational studies from Japan seem to correlate - back in 2009, researchers there noted that suicide rates decreased with higher amounts of lithium in the water (1)(In Japan, rates of suicide have been distressingly high for the past 15 years - Japan has a suicide rate of 21 per 100,000 individuals per year vs. the US rate of 11 per 100,000 (3)).  And, with the newest paper, longevity in Japan increased with the amount of trace lithium in the water in humans, and the same trace amounts of lithium in a controlled experiment (equivalent to about 2mg of lithium daily) increased the lifespan of the C elegans worms (2)(due to the increased suicide rates in Japan, suicide was controlled for in the numbers, and lithium still seemed to increase longevity in the observational studies.).

So, all old, that is rather interesting.  Trace amounts of lithium seem to improve human behavior in general, and no one knows why. 

Basic science time - lithium looks a lot like sodium.  It has the same number of electrons in the outer shell - the molecule itself is a bit smaller, but the kidneys don't seem to be able to tell the difference.  And, perhaps, neither do the neurons.  So the addition of a bit of lithium to the matrix will decrease the overall sodium gradient in the brain, decreasing neuroxicity, and increasing the efficiency of brain energetics. From the Japanese drinking water, lithium, and suicide study:

It can be speculated that very low but very long lithium exposure can enhance neurotrophic factors, neuroprotective factors and/or neurogenesis, which may account for a reduced risk of suicide.

In addition, lithium is thought to modulate the system of second messengers in the brain, meaning they enhance certain signaling processes.

The authors of these studies get rather enthusiastic, recommending supplementation at a level of about 2mg per day for human populations with the proposed effect to control behavior, increase longevity, and reduce suicide.

On the negative side, some Swedish researchers tested thyroid effects of trace lithium in the water in some villages in the Peruvian Andes (3).  Some of these villages had some 10-20X the natural lithium in the food and water of the Japanese subjects, up to a maximum of 30mg daily (which is, of course, within an order of magnitude of the pharmacologic dose of 300mg).  They found that lithium in the water seemed to decrease active thyroid hormone levels and increase thyroid stimulating levels - lithium as a medicine will tend to cause hypothyroidism.

In another interesting tidbit, they found that natural selenium levels in the water correlated with free T4 thyroid levels.  Only, thing is, selenium is supposed to act to help T4 become active thryoid hormone, T3.  So one would expect selenium levels to correlate with T3 levels and inversely correlate with T4. 

So, all told, lithium is a natural component of drinking water, and observationally decreases suicide and general naughtiness, and increases longevity, but perhaps also decreases thyroid function. 

Something to ponder.

26 comments:

  1. It seems like all these trace minerals have a pretty U-shaped curve. Not that there's been much research to define the parameters of these curves, compared to, say, proving salt is unhealthy.

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  2. Cool stuff--this* ties into the above and your post "Basic Science - Energy is Everything." Replacing sodium with lithium inhibits acetylcholine synthesis in nerve terminals, and Li2CO3 decreases t3 [in mice]. I think I saw a follow-up study where 2% of people on Li therapy had "hypothyroidism."

    *http://www.ncbi.nlm.nih.gov/pubmed/143178

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  3. Hi Dr. Deans,

    Thanks for commenting about this study. I did a quick web search about my local city tap water, and found that it is "soft" with only 25-40 ppm of dissolved minerals. Not sure how this translates out to lithium content, but sounds like it would be very low. In your opinion, would there be any risk (other than the mentioned hypothyroidism) with supplementing with a 5 mg daily dose of lithium aspartate? A paleo diet along with seaweed, Vitamin D, and magnesium supplementation has worked wonders on my chronic and seasonal depression, but a little extra positive boost would be great.

    As always, I really appreciate your informative and enjoyable posts!

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  4. Hi Clarissa - the 2009 study was criticized because it didn't include lithium in foods. According to this Internet article, anyway, eggs, milk, and seafood including seaweed are good sources. Minerals are minerals, really, and for the most part they seem to be birds of a feather (what also bugs me about these studies is that, except for the thyroid study where they measured a number of trace minerals, there don't seem to be measures of other minerals - like magnesium, for example, which would also have biologically plausible behavioral effects. So I would eat a nutrient rich diet (as it sounds that you are doing) and I bet a safe amount of trace lithium will come along for the ride.

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  5. Shoot, I forget there is a bug with the iPad so I can't cut and paste to comments, I just googled lithium rich foods and a number of articles came up.

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  6. Thank you so much for your reply, Dr. Deans. My husband was just commenting about how much better my depression has been this winter since starting a paleo diet. Have a great weekend!

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  7. Interesting! As the member of an IP3/Ca2+ lab, my most common non-psychiatric association of lithium is as a treatment to decrease PIP2 formation and thus cause IP3 depletion (yay for alphabet soup!). A quick Lithium/IP3 search brought me to this:

    Inositol and IP3 levels regulate autophagy: biology and therapeutic speculations.
    http://www.ncbi.nlm.nih.gov/pubmed/16874097
    (It is a follow up to this original finding: http://stke.sciencemag.org/cgi/content/abstract/sigtrans;2005/304/tw349 )

    I'll admit that I'm impressed the author put 'speculations' right up there in the title!

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  8. Yes, the longevity angle does seem to suggest an autophagy route. I wonder if neurogenerarion and repair. would explain the antisuicide and behavioral effects. The antisuicide effect can be quite marked clinically - even at the lowest available pharmacological dose. Too bad we have no human studies at the microdoses. Lithium is cheap cheap cheap and a 2 mg supplement trial in a prison population, for example, seems like a no brainer to at least attempt for behavioral improvement. Something tells me prison food is micronutrient poor.

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  9. Is there a believable test for lithium deficiency? Might be interesting for people to experiment with a low dose if they had reason to believe they were not replete. I also wonder if anyone has established whether or not psychiatric patients who respond to lithium are deficient compared to healthy people.

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  10. William - as far as I know there is no test for lithium deficiency. The test we use for measuring lithium levels is for phamacologic doses - for bipolar disorder a dose is typically 900-1500 mg daily, and that will typically land you a trough blood level of between 0.6 and 1. Tests generally don't measure anything less than 0.3. A 2mg dose would be well, well beneath 0.3.

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  11. I am familiar with the mecanism by which lithium depletes inositol levels. This is concerning and perplexing as low inositol levels are implicated in anxiety and depressive disorders. Speaking personally I have seen tremendous mental health benefit by supplementing 4800 mg of inositol per day. In addition to depression (mild bipolar?) I have a history of obesity, blood glucose dysregulation, and PCOS.

    The relationship between PCOS and inositol deficiency is very clear; women with PCOS seem to not properly make d-chiro-inositol (a metabolite of myo-inositol, the sort you buy OTC) and this causes ovulatory dysfunction which turns into cystic follicles and significant endocrine disorder. D-chiro-inositol, along with proper catecholamine stimulation in the ovary, is necessary for ovulation to complete successfully.

    The research on inositol as an important mediator of normal insulin receptor and serotonin receptor function is well established. Again, I have seen tremendous mental health benefits. Seroquel and abilify could not do what inositol did.

    Perhaps I respond so well because I am inositol deficient (as evidenced by my history of PCOS/glucose disorder/depression).

    I am concerned that many take lithium for exhibited behavior, but then gradually begin to experience signs of inositol deficiency like psoriasis, type 2 diabetes/hypoglycemia, and worsening of depressive tendency.

    They say lithium is antidepressant but considering what I know about inositol I do not see how the antidepressant effect can be sustained, as inositol depletion is well implicated in serotonerigic dysfunction leading to depression and anxiety.

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  12. I'll also add that I began taking a small dose lithium supplement after reading articles about its neuroprotective effects. About 9 months later I developed an intense itching of my scalp and my hair began to thin. I visited my dermatologist who said I had no inflammatory process of the scalp; not even dandruff. I tried a hydrocortisone solution, as well as additive-free hair products, with no result. It took a while to connect the dots, but after stopping lithium, the thinning and itching has diminished. I can't swear that lithium was the culprit as it has been about two months off lithium and I still have some slight residual itching, but the change is fairly dramatic.

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    1. Was it lithium orotate? Yesterday I was at work (a co-operative grocery store) and I saw that the wellness manager had a few supplement samples on his desk. One of them was lithium orotate (5 mg). I recalled reading about low doses of lithium in drinking water when I saw it, which is why I find myself here.

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  13. Dru lithium causes skin disorders by depleting inositol.

    If you buy some inositol pills from your vitamin store, the inflammation / dryness of skin will go away.

    Thinning hair may be a sign of thyroid insufficiency, which lithium will also cause.

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  14. Yes, depending on how much you get in your food and water, a lithium supplement may go past doing any good and cause harm - even at the lowish doses in the Andes study it seemed to affect thyroid function (which could certainly cause hair loss).

    ItstheWoo - I find lithium to be a poor antidepressant but a good antisuicide drug. Hope that is clear. Could be inositol is why.

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    1. "I find lithium to be a poor antidepressant but a good antisuicide drug. Hope that is clear. "

      Yes. it's about as clean and oxymoron as I have ever seen.

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  15. At first, 7up contained lithium but the FDA had it removed. So now 900 mg daily will keep me functioning and preserve me which makes up for all those lost years.

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  16. Hi Dr Dean

    Lithium in my blood test today (for hormones) has come up quite depleted. 0.20 (base line is 0.40). I though it was elevated oestradiol that was causing my hair loss (2 years) but do you think it could be this trace element?

    thanks

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  17. Hi Dr Emily Dean

    Can I take inositol to help with my dry scalp ( a side effect from lithium)? Is Niacin the same thing as inositol?

    Thanks for your help

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  18. what about the types of lithium? Don't the different types (i.e. orotate, aspartate, carbonate) offer different bio-availabilities and thus get used up in different amounts?

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  19. Hello Emily! I wanted to ask you for an opinion because, for some strange reason, this topic of lithium levels in blood is ridiculously poorly covered on the internet.

    I have just done a blood test (I wanted to see what's going on with me since I have pretty bad depression, anxiety and mood swings).

    Everything seems to be within normal bounds except few not so important things and Lithium which was 0.15 nmol/l (European range is 0.50 - 1.20).

    Could this possibly indicate that I have some form of bipolar disorder indeed and need to go to psychiatrist?
    I plan on visiting psychiatrist anyway, but I just wanted to ask you this because it will take some time to find a good psychiatrist in my country and I am curious about this all.

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  20. Just in case anyone wanders this way again:

    Interesting notes on lithium in water and crime, etc:
    http://www.gwern.net/Nootropics#lithium
    ...... including a lively discussion in the comments
    starting here:
    http://www.gwern.net/Nootropics#comment-966728546
    (including an interjection by Yours Truly :-) )

    Cheers!

    Alan

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  21. @ Alan - fascinating website. Thanks for the link.

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  22. Dear Dr. Deans:

    After reading “Should We All Take a Bit of Lithium?” By ANNA FELS in the New York Times SEPT. 13, 2014, I began doing internet research on lithium. The most useful articles I came across were your “Could You Have a Lithium Deficiency? in Psychology Today and “Evolutionary Psychiatry: Lithium and Longevity.”

    I have three questions: if you can be kind enough to respond

    First, you wrote that “to put things into perspective, a high lithium water content translates to about 2mg of lithium a day. Psychiatric doses start at 300mg daily.”

    We use or consume water in many different ways for many purposes. So in an area with high lithium water content how much water would someone have to drink to get 2mg of lithium a day? That is, how many gallons or drinking water would one have to drink to get 2mg of lithium a day? How much water is that?

    Second, there are many sellers of Lithium on the market and available without a prescription. They are not elemental high-dose lithium which is available only by prescription. Low-dose lithium aspartate or lithium orotate capsules or tablets are available from a few natural food stores and even at Amazon. But a 130 mg capsule contains only 4.8 mg of elemental lithium.

    Do you think these low dose brands are or can be helpful as mood stabilizers, to mitigate depression and anxiety or help prevent suicide?

    Finally, if so, for non-prescription brands waht is the difference between lithium aspartate and lithium orotate and why would a consumer choose one over the other?

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  23. Thanks Allan. That link us utter insanity. This guy needs to get a LIFE!

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  24. > Now to put things into perspective, a high lithium water content translates to about 2mg of lithium a day. Psychiatric doses start at 300mg daily.

    You're conflating elemental lithium and lithium carbonate dosages. Lithium carbonate is about 19 % elemental lithium by mass, so a dosage of 300 mg/d elemental lithium would require 1579 mg/d lithium carbonate, which is far higher than any minimal dosage in psychiatry. On the other hand, 300 mg lithium carbonate would contain 57 mg elemental lithium.

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