Lithium in ground-water and well-being

Lithium is a well-known mood stabilizer & suicide preventive; some research suggests lithium may be a cognitively-protective nutrient and at the population level, chronic lithium consumption (through drinking water) predicts lower levels of mental illness, violence, & suicide.
nootropics, psychology, statistics, meta-analysis, bibliography
2010-10-142019-12-07 in progress certainty: unlikely importance: 9

The metal lithium is a well-known mood sta­bi­lizer & sui­cide pre­ven­tive widely used in psy­chi­a­try. It is also a trace min­eral present to var­i­ous lev­els in all drink­ing wa­ter and much food. A long-run­ning but ob­scure vein of re­search spec­u­lates on whether lithium is ben­e­fi­cial and a nu­tri­ent, specifi­cal­ly, cog­ni­tive­ly-pro­tec­tive. Epi­demi­o­log­i­cal re­search has cor­re­lated chronic lithium con­sump­tion through drink­ing wa­ter with a num­ber of pop­u­la­tion-level vari­ables like rates of men­tal ill­ness, vi­o­lence, & sui­cide. If causal, lithium should be re­garded as a vi­tal nu­tri­ent for men­tal health and added to drink­ing wa­ter to sub­stan­tially im­prove pop­u­la­tion-wide out­comes.

How­ev­er, the ev­i­dence is weak. Most of this re­search is cross-sec­tion­al, only some is lon­gi­tu­di­nal, none offers par­tic­u­larly strong causal ev­i­dence us­ing nat­ural ex­per­i­ments or other de­signs, there are ques­tions about con­found­ing with au­to­cor­re­lated spa­tial prop­er­ties such as al­ti­tude, and some of the best re­search, us­ing Scan­di­na­vian pop­u­la­tion reg­istries, offers more mixed eval­u­a­tions of claimed cor­re­lates.

It is un­likely that fur­ther such cor­re­la­tional re­search will re­solve the de­bate, de­spite the mount­ing op­por­tu­nity cost. I sug­gest that for­mal ex­per­i­men­ta­tion is re­quired, and con­cerns about harms from lithium sup­ple­men­ta­tion mak­ing ex­per­i­ments ‘un­eth­i­cal’ can be cir­cum­vented by in­stead re­mov­ing lithium or look­ing for nat­ural ex­per­i­ments with cause changes (such as changes or up­grades to wa­ter treat­ment plants or plumb­ing mod­ify lithium con­cen­tra­tion).

The el­e­men­tal metal (re­view; FDA ad­verse events) is a pretty un­usual sub­stance and like caffeine and the am­phet­a­mi­nes, ques­tion­ably clas­si­fied as a nootrop­ic. As a met­al, lithium is dan­ger­ous at many dos­es. It’s fa­mously used for man­ic-de­pres­sion and some other dis­or­ders, but the doses are large and verge on the point where ‘the cure is worse than the dis­ease’. Most lithium re­search fo­cuses on these larger dos­es, so one has to parse ci­ta­tions care­fully to see whether it is telling one some­thing use­ful about the low lev­els one might use for sup­ple­ments or just re­in­forc­ing what one al­ready knew (‘large doses are dou­ble-edged swords’).

So, on the pos­i­tive side:

One of the main prob­lems with in­fer­ring that lithium causes these re­duc­tions is that it seems diffi­cult to rec­on­cile with how large the doses must be to treat men­tal ill­ness:

  1. most s tend to have rel­a­tively sim­ple curves which look like U-curves or V-curves or straight lines, where the effect di­min­ishes fast when you move away from the best dose;
  2. the psy­chi­atric-use­ful doses are some­thing like 100x the higher ground­wa­ter dos­es;
  3. so for most such curves, if the peak is at X mg, then a dose at X/100 or X/1000 mg will do lit­tle;
  4. any effects in the pop­u­la­tion should be ~0, and thus nearly im­pos­si­ble to de­tect,
  5. but the cor­re­lates are often found, and if causal, would be large re­duc­tions in crime/­sui­cide/­men­tal-ill­ness rates / large effects in the pop­u­la­tion;
  6. 4 & 5 seem to be con­tra­dic­to­ry.

The best re­sponses seem to be that ei­ther lithi­um’s effects di­min­ish quite grad­u­ally so that small ground­wa­ter doses can still have a mean­ing­ful pop­u­la­tion effect (negate #1), that ground­wa­ter doses are more effec­tive than one would ex­pect com­par­ing to psy­chi­atric doses of lithium car­bon­ate (per­haps due to chronic life­long ex­po­sure; negate rel­e­vance of #2/3), or that lithium may have mul­ti­ple mech­a­nisms one of which kicks in at psy­chi­atric dose lev­els and the other at ground­wa­ter lev­els (some­what sup­ported by some psy­chi­atric ob­ser­va­tions that de­pres­sives seem to ben­e­fit from lower doses but in differ­ent ways; negate #1 in a differ­ent way).

Ken Gill­man, echo­ing the ear­lier crit­i­cisms of the Ohgami et al 2009 cor­re­la­tion by , crit­i­cizes the cor­re­la­tions as gen­er­ally in­valid due to the small­ness of the drink­ing wa­ter dose com­pared to the di­etary doses of lithi­um; I dis­agree inas­much as lithium doses are cu­mu­la­tive, Schrauzer 2002 re­ports an FDA es­ti­mate of daily Amer­i­can lithium con­sump­tion 1mg, points out that nat­ural lev­els can reach as high as 0.34mg via drink­ing wa­ter, Daw­son 1991 finds Tex­ans’ lithium ex­cre­tion to “vary in­versely with rain­fall, re­flect­ing the di­lu­tion of drink­ing wa­ter sup­plies” (see also Daw­son 1970), and Daw­son et al 1972 di­rectly com­pared lithium lev­els in county wa­ters with urine lithium mea­sure­ments and found a clean lin­ear re­la­tion­ship as ex­pect­ed. These points sug­gest strongly that Gill­man is wrong to think that con­sump­tion of bot­tled wa­ter or im­ported veg­eta­bles would swamp any con­tri­bu­tion from drink­ing wa­ter - ran­dom noise can­cels out, and small cor­re­la­tions can be de­tected us­ing very large sam­ples like state or na­tion level sam­ples. (One com­menter has sug­gested that the dark­ness caused by rain is what in­creases sui­cide rates, not the di­lu­tion of nat­ural lithium in the drink­ing wa­ter; this seems un­likely as it would be in­con­sis­tent with the known when there is lit­tle dark­ness, and with the lack of cor­re­la­tion of life sat­is­fac­tion with daily weather.)

The crit­i­cisms of the trace lithium cor­re­la­tion seem weak to me, and even keep­ing in mind the that the over­whelm­ing ma­jor­ity of cor­re­la­tions dis­ap­pear when ex­per­i­men­tally tested (a 1% chance is a rea­son­able guess at the true a pri­ori odd­s), the po­ten­tial ben­e­fits seem so over­whelm­ing that I am puz­zled that, in the 42+ years since the cor­re­la­tion was first not­ed, no one has done a sim­ple ex­per­i­ment of ran­dom­iz­ing some coun­ties and in­creas­ing their trace lithium con­cen­tra­tions within the nor­mal range of nat­ural vari­a­tions in trace lithium con­cen­tra­tions. A quick es­ti­mate for what I mean. In Daw­son et al 1972, the coun­ties in the high­est lithium cat­e­gory had 30% of the men­tal hos­pi­tal ad­mis­sions that the low­est lithium coun­ties did; the USA spends some­thing like $60b an­nu­ally on men­tal health is­sues (the NYT quotes $150b gov­ern­ment ex­pen­di­ture & $500b so­ci­ety-wide cost­s). If the re­duc­tion in ad­mis­sions was equiv­a­lent to a re­duc­tion in the un­der­ly­ing dis­or­ders and ex­pen­di­tures scale ex­actly with num­ber of dis­or­ders, then lithiz­ing the USA would reap gains of some­thing like $35b an­nu­ally ( at 5%: ~$615b); how­ev­er, this is only the di­rect ex­pen­di­tures, ar­guably the field is un­der­funded (re­port­ed­ly, less than half the suffer­ers of men­tal ill­ness ), and of course the losses to so­ci­ety is far larger than that as peo­ples’ lives are de­stroyed, crime in­creases (with its mas­sive neg­a­tive ex­ter­nal­i­ties), ca­reers aban­doned, etc. At 1% prior odds and $615b to­tal pay­off, the ex­pected value is ~$600m; a con­clu­sive ex­per­i­ment ought to be triv­ially cheap to run (a few mil­lion­s?), since it re­quires only sup­ple­men­ta­tion of lithium at cen­tral­ized wa­ter fa­cil­i­ties, presents min­i­mal eth­i­cal con­cerns due to re­main­ing strictly within nat­ural vari­a­tion & reg­u­la­tory lim­its10 (and vastly less than peo­ple vol­un­tar­ily con­sume in bot­tled min­eral wa­ter­s), and can be an­a­lyzed us­ing only sta­tis­tics al­ready be­ing col­lected by po­lice or health de­part­ments.

(The po­ten­tial gain is large enough that, even if one ob­jected that we don’t know for sure that psy­chi­atric lithium does not im­pede cre­ativ­ity and so it is hy­po­thet­i­cally pos­si­ble that lithiza­tion would re­duce so­ci­etal cre­ativ­i­ty, the ben­e­fit prob­a­bly out­weighs the costs. An ex­am­ple: sup­pose lithiza­tion cost us one Nikola Tesla a year; as it hap­pens, an aca­d­e­mic re­searcher can be funded for life with ~$4m (fully loaded cost: ~$200k I’ve read (some rel­e­vant fig­ures), and a ~20y ca­reer - as­sum­ing no out­side earn­ings or grants or pay­ments), and us­ing the pre­vi­ous sav­ings of $30b, one could fully fund 7500 peo­ple each year to re­search and work on what­ever they want for life; is it plau­si­ble that one po­ten­tial Tesla out­weighs 7500 in­de­pen­dent effec­tive­ly-tenured re­searcher­s?)

On the null and neg­a­tive sides:

  • al­though the lithi­um-Parkin­son’s re­search with its rel­a­tively low doses is a re­minder to avoid lithium doses any­where near what is used for psy­chi­atric dis­or­ders: “In at least two known cas­es, toxic lev­els of the drug have ac­tu­ally caused Parkin­son’s.”
  • In one small hu­man trial (149 ex­per­i­men­tal, 447 to­tal se­lected from >1000) on in­ves­ti­gat­ing a 2008 pa­per’s find­ing that lithium might de­lay ALS, only the null effect was found.
  • There are se­ri­ous neg­a­tive effects to tak­ing a lot of lithium - 2-4 grams will trash your long-term mem­ory and sim­i­lar doses have been linked with many cog­ni­tive is­sues.
  • Tsaltas et al 2008 says many stud­ies can’t be gen­er­al­ized to healthy pop­u­la­tions; for every study find­ing dam­age to per­for­mance or mem­o­ry, there seems to be a study find­ing the null re­sult. But whichever is true, it is not en­cour­ag­ing11.
  • Of 22 Alzheimer’s pa­tients tak­ing 100mg of lithium car­bon­ate, 3 stopped due to side-effects (Mac­don­ald et al 2008); but 100mg car­bon­ate is sub­stan­tially more than 5mg oro­tate, and one might guess that old ill peo­ple would re­port more side-effects in gen­eral
  • doc­u­ments ex­treme daily con­sump­tion of 2-30mg from wa­ter & food in An­dean vil­lages, cor­re­lat­ing with changes in some thy­roid-re­lated bio­mark­ers, sug­ges­tive of po­ten­tial thy­roid is­sues
  • Apra­hamian et al 2014 was an RCT of 61 pa­tients with “mild cog­ni­tive im­pair­ment” given ~150mg of lithium car­bon­ate (tar­get­ing blood level of 0.25-0.5 mmol/L); it found min­i­mal dam­age to liver func­tion, but a few wor­ri­some sec­ondary out­comes such as some­what higher com­plaints of side-effects (4.07 vs 4.98 symp­toms)
  • Kess­ing et al 2017 finds no cor­re­la­tion be­tween bipo­lar dis­or­der & lithium in a pop­u­la­tion reg­istry study of Den­mark (de­spite bipo­lar dis­or­der be­ing one of the pri­mary uses for psy­chi­atric doses of lithi­um)


The cost of do­ing lithium sup­ple­men­ta­tion, like many other kinds of sup­ple­men­ta­tion such as , is min­i­mal in terms of raw ma­te­ri­als. A back of the en­ve­lope sug­gests that the cost in 2018 of USA-wide lithium would be <$75m for the raw ma­te­ri­als, and the cur­rent cost less than half that. So the true cost is al­most surely dom­i­nated by how­ever much work it is to ac­tu­ally add said ma­te­ri­als.

Lithium is an el­e­ment com­mer­cially mined at scale (some­thing like 40,000 ton­s/year), and even with es­ca­lat­ing de­mand, costs are still in the thou­sands of dol­lars per ton. Claims of ‘lithium short­ages’ are rel­a­tive and more of a con­cern for car man­u­fac­tur­ers us­ing po­ten­tially hun­dreds of kilo­grams per car (who will have to in­vest heav­ily in effi­ciency & sourc­ing lithium from new mines to —much like how the quickly re­sulted in them be­ing nei­ther rare nor par­tic­u­larly em­bar­goed) than sup­ple­men­ta­tion. This should be un­sur­pris­ing, as the lev­els cor­re­lated with ben­e­fits are reach­able in many places by drink­ing or­di­nary un­treated wa­ter, after all: so ei­ther there is a lot of lithium out there, the nec­es­sary lev­els are tiny, or both.

Us­ing Schrauzer as an ex­am­ple of what it’d take, Schrauzer de­fines ‘high’ as a con­cen­tra­tion of >70μg /l (ie 70 mil­lionths of a gram per liter). The USGS es­ti­mates to­tal use of all wa­ter for any pur­pose in the USA at 322 bil­lion gal­lon­s/­day, of which ~43 bil­lion gal­lon­s/­day or 162 bil­lion liter­s/­day are ‘do­mes­tic’+‘pub­lic sup­ply’.

As­sum­ing the worst case, that all of this must be sup­ple­mented and that all of it has 0μg /liter lithium and must be sup­ple­mented by 70μg/liter, then the to­tal lithium re­quired per day is kilo­grams, or 4,141,935 kilo­grams per year, or 4,565 tons per year.

At its 2018 peak, which trig­gered alarmism over short­ages, high­-qual­ity bat­tery-grade lithium cost ~$16500/ton (it has since fallen as low as $7000 in 2019), so the to­tal cost per year comes to $75,322,500; or to put it an­other way, [$0.23]($2018)/year per capi­ta. For fur­ther per­spec­tive, the US fed­eral gov­ern­ment uses which are >$10.37$7.92010m, and the life­time costs of dis­eases like schiz­o­phre­nia or the cost of crimes typ­i­cally come in at or­ders of mag­ni­tude around $1m or high­er.

This as­sumes lithium prices don’t fall fur­ther, that all wa­ter must be fully sup­ple­ment­ed, etc, and is a loose up­per bound. A more rea­son­able cost would use long-range fore­casts ex­trap­o­lat­ing with & economies of scale, the abil­ity to use the low­est­-qual­ity & cheap­est lithium sources (minute differ­ences in pu­rity or type are crit­i­cal to bat­ter­ies but not sup­ple­men­ta­tion) and tar­get wa­ter sup­plies most likely to be drunk, and re­al­is­tic es­ti­mates of how much wa­ter ac­tu­ally needs to be sup­ple­ment­ed; it will likely be a small frac­tion of [$0.23]($2018)/year, and quite pos­si­bly down in the <[$0.05]($2018) range. (Just us­ing a more re­cent price per ton would more than halve the es­ti­mate, after al­l.)

And of course, just be­cause the ex­ist­ing epi­demi­o­log­i­cal ev­i­dence fo­cuses on drink­ing wa­ter (due to the rel­a­tive ease of mea­sure­ment) does­n’t mean that sup­ple­ment­ing drink­ing wa­ter . Great flex­i­bil­ity is pos­si­ble. Given the small quan­ti­ties in­volved, many other ap­proaches could be cheap­er: de­liv­ery via salt like iodine, for­ti­fi­ca­tion of flour like iron, for­ti­fi­ca­tion of milk like vi­t­a­min D, long-last­ing in­jec­tions like io­dine or vi­t­a­min D for cases where reg­u­lar sup­ple­men­ta­tion is in­fea­si­ble, ad­di­tion to mul­ti­-vi­t­a­mins like vi­t­a­min A or the B vi­t­a­mins…

So, cost is not a ma­jor ob­jec­tion to lithium sup­ple­men­ta­tion.

  1. From Tsaltas 2008, pg 15:

    Ten­ta­tive con­clu­sions from stud­ies in nor­mal sub­jects are that acute lithium does not affect short­-term mem­o­ry; sub­chronic ad­min­is­tra­tion spares ba­sic short­-term mem­ory of on­go­ing events but higher task de­mands (as in neu­ropsy­cho­log­i­cal test­ing) oc­ca­sion­ally re­veal mild deficits. As do learn­ing deficits, these too ap­pear tran­sient. A sim­i­lar pic­ture emerges with re­spect to lithium effects on hu­man long-term re­call. In an­i­mal stud­ies, sub­chronic and chronic lithium with clin­i­cally rel­e­vant serum lev­els does not affect spa­tial ref­er­ence or ob­ject recog­ni­tion mem­ory and ac­tu­ally en­hances work­ing mem­ory un­der cer­tain con­di­tions. This is con­sis­tent with re­cent clin­i­cal MRI find­ings not­ing im­proved im­me­di­ate ver­bal mem­ory after a 4-year pe­riod of lithium treat­ment, along with MRI ev­i­dence of in­creased hip­pocam­pal vol­ume over the same pe­ri­od.

    Hu­man at­ten­tion is quite con­sis­tently re­ported nor­mal un­der lithi­um. Some older an­i­mal stud­ies re­port nar­row­ing of at­ten­tion onto high­-salience cues and com­pro­mised la­tent in­hi­bi­tion, but these re­sults are chal­lenged by more re­cent data in­di­cat­ing nor­mal func­tion. Fi­nal­ly, in­for­ma­tion on lithium effects on ex­ec­u­tive func­tions is sparse and can­not be eval­u­ated at pre­sent. More ba­sic re­search is defi­nitely needed with re­spect to lithium effects on at­ten­tion and ex­ec­u­tive func­tions. Re­cent re­ports on lithium effects on the cog­ni­tive-be­hav­ioral deficits in­duced by var­i­ous chal­lenges to the ner­vous sys­tem in an­i­mal mod­els are quite promis­ing. Lithium pro­tects against neu­roanatom­i­cal and neu­ro­chem­i­cal effects and also mod­er­ates cog­ni­tive deficits in­duced by stress or CNS trauma such as ir­ra­di­a­tion or anox­ia. In some cas­es, such deficits are not sim­ply pre­vented but ap­pear to be re­versed post fac­to. This com­bined neu­ro­pro­tec­tive- and cog­ni­tive-en­hanc­ing ac­tion of lithium is noted pri­mar­ily with re­spect to hip­pocam­pally re­lated spa­tial mem­ory tasks. It ap­pears to in­volve pro­tec­tion against the re­duced cell pro­lif­er­a­tion and in­creased apop­totic rate noted mainly in the hip­pocam­pus un­der these chal­lenges…

  2. Tsaltas 2008, con­tin­ued:

    A sim­i­lar pic­ture emerges in re­la­tion to lithium effects on the cog­ni­tive com­pro­mises in­duced by neu­rode­gen­er­a­tive dis­or­ders. Lithium re­duces the preva­lence of Alzheimer’s dis­ease in bipo­lar pa­tients, and there is ev­i­dence sug­gest­ing that this is as­so­ci­ated with re­duced GSK-3beta ex­pres­sion. Ev­i­dence of lithi­um’s mod­er­at­ing ac­tion on hip­pocam­pally re­lated cog­ni­tive deficits also comes from trans­genic an­i­mal mod­els of Alzheimer’s dis­ease…In cog­ni­tive dys­func­tion as­so­ci­ated with psy­chi­atric con­di­tions, ben­e­fi­cial effects of lithium have emerged on the neu­roanatom­i­cal level from imag­ing stud­ies. Lithium treat­ment of bipo­lar pa­tients has been as­so­ci­ated with hip­pocam­pal vol­ume in­crease and ap­pears to en­tail con­comi­tant cog­ni­tive im­prove­ments. These neu­roimag­ing find­ings are not lim­ited to bipo­lar pa­tients, but in­volve peo­ple at ul­tra­high risk of de­vel­op­ing a psy­chotic dis­or­der where lithium ap­pears to ar­rest neu­roanatom­i­cal and neu­ro­chem­i­cal changes as­so­ci­ated with the on­set of psy­chosis. In con­clu­sion, in­creas­ing neu­roanatom­i­cal and neu­ro­chem­i­cal ev­i­dence from both in vitro and in vivo stud­ies sup­ports that lithium has neu­ro­pro­tec­tive prop­er­ties, mainly in­volv­ing hip­pocam­pal cells (Moore et al. 2000; Manji et al. 2001; Sassi et al. 2002; Kim et al. 2004; Chuang 2004; Chuang and Priller 2006).

  3. A close­ly-re­lated Texas study found sim­i­lar in­verse cor­re­la­tions for men­tal hos­pi­tals, but I haven’t been able to find full­text: “The re­la­tion­ship of tap wa­ter and phys­i­o­log­i­cal lev­els of lithium to men­tal hos­pi­tal ad­mis­sion and homi­cide in Texas”, Daw­son, in Lithium in Bi­ol­ogy and Med­i­cine 1991. An odd re­sult is de­creased lithium lev­els in autis­tic chil­dren and also their moth­ers, Adams et al 2006.↩︎

  4. A mouse study found lithium re­duced ag­gres­sion in one mouse breed: “Effects of nu­tri­tional lithium de­fi­ciency on be­hav­ior in rats”, Klem­fuss & Schi­rauzer 1995↩︎

  5. Two ear­lier stud­ies: “The math­e­mat­i­cal re­la­tion­ship of drink­ing wa­ter lithium and rain­fall to men­tal hos­pi­tal ad­mis­sion”, “Re­la­tion­ship of lithium me­tab­o­lism to men­tal hos­pi­tal ad­mis­sion and homi­cide” (which used di­rectly mea­sured lithium lev­els via urine sam­ples).↩︎

  6. In­for­mal­ly, the chemist William Walsh found by 1983 that among his other re­sults from hair analy­sis, lithium was low in his stud­ied in­mates as well. Some stud­ies cite an un­pub­lished Walsh man­u­script, “Chem­i­cal im­bal­ance and crim­i­nal vi­o­lence: re­sults of two con­trolled stud­ies of Cal­i­for­nia in­sti­tu­tions”, held at the “Health Res. In­sti­tute, Chicago”.↩︎

  7. Kabacs et al 2011 turns in the ex­pected neg­a­tive point value (r = -0.03), but it is not sta­tis­ti­cal­ly-sig­nifi­cant. It’s not clear how much of a coun­ter-ex­am­ple this is; the cor­re­la­tion is sim­ple with­out any ad­just­ments for other fac­tors (like Ka­pusta et al 2011 did), and there’s an is­sue of range re­stric­tion: the au­thors write “In the East of Eng­land, there was rel­a­tively lit­tle vari­a­tion in pop­u­la­tion size across the 47 sub­di­vi­sions. Al­so, the lithium lev­els in drink­ing wa­ter in Texas and in the Oita pre­fec­ture ranged from 0 to 160 μg/l, and 0.7 to 59 μg/l, re­spec­tive­ly. These val­ues rep­re­sent a much wider range and higher top level than those found in the East of Eng­land (<1-21 μg/l).” Pom­pili has a sim­i­lar prob­a­ble power is­sue: they don’t reach sta­tis­ti­cal-sig­nifi­cance over­all with their 145 sites but they do in one sub­group and the over­all re­la­tion­ships are al­ways in­verse as pre­dicted (in the 3 decades, the over­all r was -0.081, -0.099, & -0.039); sug­gest­ing to me that here again we may have an is­sue of in­suffi­cient power to de­tect a fairly small effect and that a meta-analy­sis may con­firm the cor­re­la­tion.↩︎

  8. Re­views: , Baldessarini et al 2006, & Guzzetta et al 2007, Le­witzka et al 2015.↩︎

  9. Fa­jardo et al 2018 notes that the al­l-cause mor­tal­ity re­duc­tion loses sta­tis­ti­cal-sig­nifi­cance after con­trol­ling for sui­cide rates, but do not do a for­mal me­di­a­tion test.↩︎

  10. A ran­dom­ized ex­per­i­ment could be con­ducted ei­ther by adding ad­di­tional lithium to drink­ing wa­ter, re­main­ing be­low the reg­u­la­tory lim­its, or al­ter­nate­ly, by pre­vent­ing in­creases in lithium lev­els some­how. The for­mer is prob­a­bly much eas­ier in prac­tice. Eth­i­cal­ly, there should be no prob­lem: if it’s un­eth­i­cal to add any lithium to wa­ter (any­where up to the FDA-approved safe lev­el­s), then by sym­me­try & the re­ver­sal test does­n’t that im­ply there is an eth­i­cal duty to con­trol cur­rent­ly-nat­u­ral­ly-vary­ing lithium lev­els to even lower lev­els than cur­rently al­lowed?↩︎

  11. Tsaltas et al 2008, pg 15:

    The effects of lithium on learn­ing in clin­i­cal pop­u­la­tions ap­pear to be mildly detri­men­tal, pos­si­bly at­trib­ut­able to lithi­um’s gen­er­al­ized damp­en­ing effect on per­for­mance. They ap­pear most pro­nounced in the ini­tial stages of lithium ad­min­is­tra­tion, as cor­rob­o­rated by an­i­mal stud­ies. There­fore, re­sults pro­duced by sub­chronic regimes should be treated cau­tious­ly, as per­haps re­flect­ing gen­eral in­flu­ences on arousal and mood.