Lithium Supplementation

An interesting opinion piece appeared in the New York Times today, suggesting that we supplement the drinking water supply with small doses of lithium to reduce the prevalence of mental health issues.

That sounds crazy.

My brain immediately associates lithium with lobotomies, straight jackets, and insane asylums.  Upon further research, these associations aren't fair: lithium was first experimented with in the straight-jacket-and-insane-asylum late 1800's, but in the 1950's it was rediscovered and became one of the first psychiatric pharmacological success stories.

As it turns out, lithium is naturally present in the Earth's crust at around 20 mg/kg and makes it into our drinking water at concentrations up to 0.2 mg/L.

Lithium in Medicine

Long before the modern psychiatric applications, the ancient Greeks presecribed lithium-rich spring waters for the treatment of a variety of mental ailments.

In modern psychiatry, high-dose lithium is prescribed for bipolar disorder and severe depression, usually in the form of lithium carbonate (100-2000mg, 18.8% Li → 20-375mg of pure Li).

Recently, the neurotropic and neuroprotective properties of low-dose lithium (25-120 mg lithium orotate, 4.3% Li → 1-5mg Li) in both acute (e.g. stroke) and chronic (e.g. depression, dementia) contexts have been evaluated. Studies have also correlated higher levels of natural lithium in the water supply with reduced rates of suicide and violent crime in Texas, Japan, Greece, and Austria. Low-dose lithium has no side effects, and these results have led some researchers to suggest supplementing the water supply in low-lithium region:

Big Think: Drug Our Drinking Water (with Lithium)
Psychology Today: Could You Have a Lithium Deficiency?

It has even been proposed that lithium is an essential nutrient with a Recommended Dietary Allowance (RDA) of 1 mg per day.

Lithium in the Literature

It's an understatement to say that there's a lot out there on the pharmacology and biochemistry of lithium, especially in the last ten years.  The literature is dominated by clinical psychiatrists evaluating high-dose lithium for the treatment of bipolar disorder, but interest in lithium's neuroprotective mechanism and potential alternative applications is growing:
Lithium-induced increase in human brain grey matter.
Moore, G. J., Bebchuk, J. M., Wilds, I. B., Chen, G., & Menji, H. K. (2000). 
The Lancet, 356(9237), 1241–1242.

Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of 
bcl-2’s neurotrophic effects? 
Moore, G. J., Bebchuk, J. M., Hasanat, K., Chen, G., Seraji-Bozorgzad, N., Wilds, I. B., 
… Manji, H. K. (2000). 
Biological Psychiatry, 48(1), 1–8.

Mood stabilizers: protecting the mood...protecting the brain.
Brunello, N. (2004). 
Journal of Affective Disorders, 79 Suppl 1, S15–20.

Lithium: the pharmacodynamic actions of the amazing ion.
Brown, K. M.; Tracy, D. K. (2013)
Ther. Adv. Psychopharmacol. 2013, 3, 163–176

Lithium: Occurrence, Dietary Intakes, Nutritional Essentiality.
Schrauzer, G. N.
J. Am. Coll. Nutr. 2002, 21, 14–21

The neurotrophic and neuroprotective effects of psychotropic agents.
Hunsberger, J., Austin, D. R., Henter, I. D., & Chen, G. (2009). 
Dialogues in Clinical Neuroscience, 11(3), 333–48. 

Lithium at 50: have the neuroprotective effects of this unique cation been overlooked?
Manji, H. K., Moore, G. J., & Chen, G. (1999). 
Biological Psychiatry, 46(7), 929–40.

Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: 
implications for the pathophysiology and treatment of manic–depressive illness.
Manji, H. K., Moore, G. J., & Chen, G. (2000). 
Biological Psychiatry, 48(8), 740–754. 

Lithium up-regulates the cytoprotective protein Bcl-2 in the CNS in vivo: a role for neurotrophic 
and neuroprotective effects in manic depressive illness.
Manji, H. K., Moore, G. J., & Chen, G. (2000). 
The Journal of Clinical Psychiatry, 61 Suppl 9(suppl 9), 82–96.

Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics 
for Difficult-to-Treat depression.
Manji, H. K., Quiroz, J. a, Sporn, J., Payne, J. L., Denicoff, K., A. Gray, N., … Charney, D. S. (2003). 
Biological Psychiatry, 53(8), 707–742. 

Overview of the mechanism of action of lithium in the brain: fifty-year update.
Lenox, R., & Hahn, C. (2000). 
Journal of Clinical Psychiatry, 6140(suppl 9).

The psychopharmacologic specificity of the lithium ion: origins and trajectory.
Soares, J. C., & Gershon, S. (2000). 
The Journal of Clinical Psychiatry, 61 Suppl 9(suppl 9), 16–22.

Beneficial effects of mood stabilizers lithium, valproate and lamotrigine in experimental stroke models.
Wang, Z., Fessler, E. B., & Chuang, D.-M. (2011). 
Acta Pharmacologica Sinica, 32(12), 1433–45.

Neurotrophic signaling cascades are major long-term targets for lithium: clinical implications.
Yuan, P., Gould, T.D., Gray, N.a., Bachmann, R.F., Schloesser, R.J., Lan, M.J.K., … Manji, H.K. (2004). 
Clinical Neuroscience Research, 4(3-4), 137–153.

Lithium Dietary Supplements

Low-dose lithium does not appear to be a very popular supplement, probably due to the negative connotations of its association with mental disorders. The most common form appears to be lithium orotate 120-130mg, providing 5mg of pure lithium (i.e. one-quarter to one-hundredth the usual psychiatric doses) for about eight cents a pill:
Taking one of these pills is the equivalent of drinking about 50L of water from a naturally high-lithium region.  Lithium-rich spring water is also sold under the venerable 'Lithia' brand, but its lithium concentration is quite low (0.5 mg/L) and shipping around all of that water is expensive.

In the aftermath of this NYT article, I bet demand for lithium supplements increases greatly and the prices go up!

Should you buy some?  At seven cents a pill, can't hurt / might help... but I'm not a doctor, so you'll have to look over the evidence and make your own decision.  Don't trust anything you read in some random blog!  ;)

This topic has a page on the BC Wiki: Lithium Supplementation.