Iodine and Adult IQ meta-analysis

Iodine improves IQ in fetuses; adults as well? A meta-analysis of relevant studies says no.
nootropics, psychology, statistics, meta-analysis, charity, R, power-analysis, IQ, bibliography
2012-02-292017-07-18 in progress certainty: highly likely importance: 10


Iodiza­tion is one of the great suc­cess sto­ries of pub­lic health in­ter­ven­tion: iodiz­ing salt costs pen­nies per ton, but as demon­strated in ran­dom­ized & nat­ural ex­per­i­ments, pre­vents goi­ters, cre­tinism, and can boost pop­u­la­tion IQs by a frac­tion of a stan­dard de­vi­a­tion in the most iodine-d­e­fi­cient pop­u­la­tions.

These ex­per­i­ments are typ­i­cally done on preg­nant wom­en, and re­sults sug­gest that the ben­e­fits of iodiza­tion di­min­ish through­out the trimesters of a preg­nan­cy. So does iodiza­tion ben­e­fit nor­mal healthy adults, po­ten­tially even ones in rel­a­tively iodine-suffi­cient West­ern coun­tries?

Com­pil­ing ex­ist­ing post-na­tal iodiza­tion stud­ies which use cog­ni­tive tests, I find that—out­liers aside—the ben­e­fit ap­pears to be nearly ze­ro, and so likely it does not help nor­mal healthy adults, par­tic­u­larly in West­ern adults.

is in­ter­est­ing from the eth­i­cal stand­point as one of the most cost-effec­tive—yet ob­scure— mea­sures ever de­vised which de­serves a name like : a few pen­nies of io­dine added to salt elim­i­nates many cases of men­tal re­tar­da­tion & goi­ters.

Background

Sup­ple­men­ta­tion of in salt, wa­ter, or oil in­creases body io­dine lev­els and re­duces io­dine de­fi­ciency dis­or­ders (Wu et al 2002). Sup­ple­ment­ing, dur­ing preg­nancy or in­fan­cy, can raise av­er­age IQs in the worst-off re­gions by <13 IQ points1 (close to a full stan­dard de­vi­a­tion); such an in­crease is of con­sid­er­able eco­nomic val­ue, even in de­vel­oped coun­tries with iodiza­tion pro­grams (see & ap­pen­dices for a cost-ben­e­fit analy­sis). In an ad­di­tional bonus for our post-fem­i­nist so­ci­ety, fe­males ben­e­fit more from iodiza­tion than males2. Be­cause salt pro­duc­tion is gen­er­ally so cen­tral­ized as a bulk com­mod­ity ex­tracted from a very few ar­eas, iodiza­tion is al­most triv­ial to im­ple­ment. (Although hu­mans be­ing hu­mans, there are ob­sta­cles even to suc­cess­ful iodiza­tion pro­grams3.)

Cre­tinism is only the most ex­treme form of io­dine de­fi­cien­cy, al­though a ma­jor & worth­while hu­man­i­tar­ian task; io­dine cor­re­lates with IQ in non-d­e­fi­cient chil­dren, eg. Japan is si­mul­ta­ne­ously one of the longest-lived & high­est IQ coun­tries in the world and one of the great­est con­sumers of io­dine4 (from sea­weed, prin­ci­pal­ly, lev­els so high they sug­gest that cur­rent rec­om­men­da­tions are overly con­ser­v­a­tive), and even weak hy­pothy­roidism im­pairs men­tal per­for­mance (in the old). School is di­rectly im­pacted in ran­dom­ized tri­als; from a re­view of Poor Eco­nom­ics (Baner­jee & Du­flo 2011):

Pro­vid­ing io­dine cap­sules to preg­nant moth­ers is an in­ter­ven­tion that helps brain de­vel­op­ment in fe­tus­es. It costs around 51 cents per dose—and leads to kids who stay in school about five months longer be­cause they are cog­ni­tively bet­ter able to learn.

The orig­i­nal waves of iodiza­tion caused large-s­cale changes in: num­bers of peo­ple go­ing to school5, work­ing at all6, their oc­cu­pa­tion7, how they voted, or even how many re­cruits from a re­gion are ac­cepted to se­lec­tive flight schools8.

Of course, io­dine can be a dou­ble-edged sword. Feyrer et al 2008 men­tioned a wave of dis­or­ders after iodiza­tion of salt, as long-d­e­fi­cient thy­roids were shocked with ad­e­quate lev­els of iodine, and nat­ural io­dine lev­els can be so high as to be­gin to in­versely cor­re­late with IQ in Chi­na.9

More wor­ri­some is re­cent trends in the de­vel­oped world such as the War on Salt. Un-iodized salt or low-io­dide salt like sea salt is ever more pop­u­lar. Ex­ist­ing iodized ta­ble salt often has far less io­dide than rec­om­mend­ed, or even what the man­u­fac­turer claims it has10. Iodized salt used in cook­ing—as op­posed to a straight table-side condi­men­t—loses large chunks of its io­dine con­tent11. Small sam­ples of or­di­nary peo­ple turn in se­vere or mild io­dine de­fi­ciency rates of 67%12 to as much as 73.7%13. This is plau­si­ble given a steady sec­u­lar trend of io­dine re­duc­tion in the US (although one that seems to have paused in the 2000s)14. I was un­sur­prised to read Morse 2012:

Nu­mer­ous pop­u­la­tion stud­ies from a va­ri­ety of coun­tries in­clud­ing Chi­na, Hong Kong, Iran, In­dia, Kyr­gyzs­tan and Eng­land have re­ported io­dine de­fi­ciency in girls of child bear­ing age 76, in preg­nant 154,155,156,157, and in preg­nant and lac­ta­tion women 158,159. Some of these stud­ies in­cluded re­gions where salt iodiza­tion is prac­ticed, yet a [sub­stan­tial] pro­por­tion of preg­nant and lac­tat­ing women were still de­fi­cient 155,156,157,158,159,160,161. A few ex­am­ples of re­cent stud­ies fol­low…

This has led to an ob­serv­able im­pact on the IQ of the chil­dren of Eng­lish women (Bath et al 2013), and there is no rea­son to ex­pect the effect to be con­fined to them.

Meta-analysis

Given all this, one nat­u­rally won­ders what the effect might be in older hu­mans: el­e­men­tary school age and above. If io­dine be­fore birth can be re­spon­si­ble for in­creas­ing IQ by a full stan­dard de­vi­a­tion or more in com­bi­na­tion with iron, what about io­dine post-birth? Iron sup­ple­men­ta­tion treats and there is ev­i­dence it also treats the cog­ni­tive prob­lems as well, so what about iodine?

Liu et al 2009, and tan­gen­tial re­sults like Bonger­s-Schokking et al 2005 (where there was a dis­cernible IQ differ­ence be­tween TSH treat­ment of in­fants with con­gen­i­tal hy­pothy­roidism be­fore & after 13 days post-birth) sug­gest that the win­dow for io­dine in­ter­ven­tion may close rapidly dur­ing preg­nancy and be closed post-birth. While io­dine has been ex­ten­sively stud­ied in in­fants and other un­usual pop­u­la­tions, the nar­row ques­tion of iodine’s effect on IQ in healthy adult First World pop­u­la­tions has not been (a com­mon prob­lem in nootrop­ic­s); we are in­ter­ested in cases only where some­one is men­tally tested be­fore and after io­dine sup­ple­men­ta­tion, or where 1 co­hort re­ceives sup­ple­men­ta­tion after birth when com­pared against a sim­i­lar co­hort who re­ceive no sup­ple­men­ta­tion. Most stud­ies turn out to be ei­ther cor­re­la­tional (eg. strat­i­fy­ing by blood lev­els of thy­roid hor­mone) or com­par­ing fe­tal sup­ple­men­ta­tion against a non-sup­ple­mented con­trol group. Un­for­tu­nate­ly, no study is so large and high­-qual­ity that it de­fin­i­tively re­solves our ques­tion. So we re­sort to of what is avail­able: we pool many stud­ies to­gether to de­rive a sum­mary av­er­age of the over­all re­sults, weighted by how many sub­jects each study had (s­ince more is bet­ter) ver­sus how strong a re­sult they yield­ed. An ex­am­ple of this is the meta-analy­sis & re­view, which is the clos­est ex­ist­ing study to what I want, “Io­dine and Men­tal De­vel­op­ment of Chil­dren 5 Years Old and Un­der”:

Sev­eral re­views and meta-analy­ses have ex­am­ined the effects of io­dine on men­tal de­vel­op­ment. None fo­cused on young chil­dren, so they were in­com­plete in sum­ma­riz­ing the effects on this im­por­tant age group. The cur­rent sys­tem­atic re­view there­fore ex­am­ined the re­la­tion­ship be­tween io­dine and men­tal de­vel­op­ment of chil­dren 5 years old and un­der. A sys­tem­atic re­view of ar­ti­cles us­ing MEDLINE (1980-No­vem­ber 2011) was car­ried out. We or­ga­nized stud­ies ac­cord­ing to four de­signs: (1) ran­dom­ized con­trolled trial with io­dine sup­ple­men­ta­tion of moth­ers; (2) non-ran­dom­ized trial with io­dine sup­ple­men­ta­tion of moth­ers and/or in­fants; (3) prospec­tive co­hort study strat­i­fied by preg­nant wom­en’s io­dine sta­tus; (4) prospec­tive co­hort study strat­i­fied by new­born io­dine sta­tus. Av­er­age effect sizes for these four de­signs were 0.68 (2 RCT stud­ies), 0.46 (8 non-RCT stud­ies), 0.52 (9 co­hort strat­i­fied by moth­ers’ io­dine sta­tus), and 0.54 (4 co­hort strat­i­fied by in­fants’ io­dine sta­tus). This trans­lates into 6.9 to 10.2 IQ points lower in io­dine de­fi­cient chil­dren com­pared with io­dine re­plete chil­dren. Thus, re­gard­less of study de­sign, io­dine de­fi­ciency had a sub­stan­tial im­pact on men­tal de­vel­op­ment. Method­olog­i­cal con­cerns in­cluded weak study de­signs, the omis­sion of im­por­tant con­founders, small sam­ple sizes, the lack of clus­ter analy­ses, and the lack of sep­a­rate analy­ses of ver­bal and non-ver­bal sub­tests. Quan­ti­fy­ing more pre­cisely the con­tri­bu­tion of io­dine de­fi­ciency to de­layed men­tal de­vel­op­ment in young chil­dren re­quires more well-de­signed ran­dom­ized con­trolled tri­als, in­clud­ing ones on the role of iodized salt.

But its sec­ond de­sign con­flates sup­ple­men­ta­tion of moth­ers with that of in­fants & chil­dren, and so the d = 0.46 (fig­ure 2) is not di­rectly mean­ing­ful (the au­thors note that the stud­ies are het­ero­ge­neous but do not at­tempt strat­i­fy­ing by fe­tal vs in­fan­cy). More rel­e­vant is “Effect of io­dine sup­ple­men­ta­tion in preg­nancy on child de­vel­op­ment and other clin­i­cal out­comes: a sys­tem­atic re­view of ran­dom­ized con­trolled tri­als”, Zhou et al 2013:

…Four­teen pub­li­ca­tions that in­volved 8 tri­als met the in­clu­sion cri­te­ria. Only 2 in­cluded tri­als re­ported the growth and de­vel­op­ment of chil­dren and clin­i­cal out­comes. Io­dine sup­ple­men­ta­tion dur­ing preg­nancy or the peri­con­cep­tional pe­riod in re­gions of se­vere io­dine de­fi­ciency re­duced risk of cre­tinism, but there were no im­prove­ments in child­hood in­tel­li­gence, gross de­vel­op­ment, growth, or preg­nancy out­comes, al­though there was an im­prove­ment in some mo­tor func­tions. None of the re­main­ing 6 RCTs con­ducted in re­gions of mild to mod­er­ate io­dine de­fi­ciency re­ported child­hood de­vel­op­ment or growth or preg­nancy out­comes. Effects of io­dine sup­ple­men­ta­tion on the thy­roid func­tion of moth­ers and their chil­dren were in­con­sis­tent.

They cor­rectly ob­serve that the avail­able stud­ies are not very method­olog­i­cally rig­or­ous and most do not al­low of any real analy­sis, but I think it may be worth do­ing a more per­mis­sive sum­mary and see what it says. Tay­lor et al 2014’s “Im­pact of io­dine sup­ple­men­ta­tion in mild-to-mod­er­ate io­dine de­fi­cien­cy: sys­tem­atic re­view and meta-analy­sis” looks at Gor­don & Zim­mer­man, com­bin­ing the avail­able tests and find­ing:

For the meta-analy­sis cog­ni­tive tests were cat­e­gorised into the fol­low­ing do­mains: (i) per­cep­tual rea­son­ing; (ii) pro­cess­ing speed; (i­ii) work­ing mem­o­ry; and (iv) global cog­ni­tive in­dex. The global cog­ni­tive in­dex was de­rived from the av­er­age of the scores in each of the do­mains. Un­ad­justed SMDs of the change in cog­ni­tive scores from base­line were com­puted from the raw scores re­ported by the au­thors, while ad­justed SMDs were de­rived from the re­ported mean-ad­justed treat­ment effects. s.e.m.-ad­justed treat­ment effects were cal­cu­lated us­ing the rec­om­mended for­mula in the Cochrane hand­book (44). The re­sults of the analy­sis for in­di­vid­ual do­mains are pre­sented in Ta­ble 3, while Fig. 3 shows the for­est plots for the global cog­ni­tive in­dex. Ben­e­fi­cial effects of io­dine sup­ple­men­ta­tion were seen for both ad­justed and un­ad­justed global in­dices with mild het­ero­gene­ity ob­served be­tween the stud­ies. For in­di­vid­ual un­ad­justed do­main scores, ben­e­fits were seen for pro­cess­ing speed but not for per­cep­tual rea­son­ing or work­ing mem­o­ry, while for the ad­justed do­mains io­dine was ben­e­fi­cial for per­cep­tual rea­son­ing al­though this was as­so­ci­ated with sig­nifi­cant het­ero­gene­ity.

Possible studies

I have looked at the fol­low­ing stud­ies:

  1. “Neu­ro­log­i­cal dam­age to the fe­tus re­sult­ing from se­vere io­dine de­fi­ciency dur­ing preg­nancy”, Pharoah et al 1971; “The effect of io­dine pro­phy­laxis on the in­ci­dence of en­demic cre­tinism”, Pharoah et al 1972; “Fe­tal io­dine de­fi­ciency and mo­tor per­for­mance dur­ing child­hood”, Con­nolly et al 1979; “A con­trolled trial of io­d­i­nated oil for the pre­ven­tion of en­demic cre­tinism: a long-term fol­low-up”, Pharoah & Con­nolly 1987; a 1966 Papua New Guinea trial which in 1972 be­gan sup­ple­ment­ing the con­trol group as well (who were now 0–6 years old); at the 1982 fol­lowup, the con­trol group still suffered cre­tinism and deficits com­pared to the ex­per­i­men­tal—no effect. These stud­ies turn out to not test the adults or chil­dren born be­fore iodiza­tion and so are not use­ful for our pur­pose.

  2. “Pro­phy­laxis of en­demic goi­ter with iodized oil in rural Peru”, Pretell et al 1972; “Io­dine de­fi­ciency and the ma­ter­nal-fe­tal re­la­tion­ship”, Pretell et al 1974 (see also the ret­ro­spec­tive re­view Pretell & Cac­eres 1994): a 1966 Peru tri­al; fe­males (<45 years old) and males (<18 years old); ex­per­i­men­tal in­fants did not out­per­form con­trol in­fants—no effect. These stud­ies turn out to not test the adults or chil­dren born be­fore iodiza­tion and so are not use­ful for our pur­pose.

  3. “The effects of oral iodized oil on in­tel­li­gence, thy­roid sta­tus, and so­matic growth in school-age chil­dren from an area of en­demic goi­ter”, Bautista et al. A 1982 Bo­livia tri­al; 200 school­child­ren mea­sur­ing IQ—no effect

  4. “Sup­ple­men­tary io­dine fails to re­verse hy­pothy­roidism in ado­les­cents and adults with en­demic cre­tinism”, Boy­ages et al 1990; 28 Chi­nese aged 14–52, se­verely de­fi­cient, with no gains on the “Hiskey Ne­braska Test of Learn­ing Ap­ti­tude” or the “Griffiths Men­tal De­vel­op­ment Scales”—no effect

  5. “Con­trolled trial of vi­t­a­m­in-min­eral sup­ple­men­ta­tion: Effects of in­tel­li­gence and per­for­mance”, Schoen­thaler et al 1991; mul­ti­vi­t­a­min with 0.075mg iodine, IQ gain in the 8th and 10th grader­s—ben­e­fi­cial effect

  6. “Tim­ing of Vul­ner­a­bil­ity of the Brain to Io­dine De­fi­ciency in En­demic Cre­tinism”, Cao et al 1994: 689 chil­dren 0–3 years of age, min­i­mal effect in the chil­dren

  7. “Di­etary in­take and mi­cronu­tri­ent sta­tus of ado­les­cents: effect of vi­t­a­min and trace el­e­ment sup­ple­men­ta­tion on in­dices of sta­tus and per­for­mance in tests of ver­bal and non-ver­bal in­tel­li­gence”, Southon et al 1994: 13–15 year olds with a mul­ti­vi­t­a­min of things in­clud­ing io­dine (0.15mg); no effect on IQ test

  8. “Effect of io­dine and iron sup­ple­men­ta­tion on phys­i­cal, psy­chomo­tor and men­tal de­vel­op­ment in pri­mary school chil­dren in Malawi” (mir­ror), Shrestha 1994

  9. “Effect of iodized oil sup­ple­men­ta­tion on thy­roid hor­mone lev­els and men­tal per­for­mance among Orang Asli school­child­ren and preg­nant moth­ers in an en­demic goitre area in Penin­su­lar Malaysia”, Isa et al 2000

  10. “Im­proved io­dine sta­tus is as­so­ci­ated with im­proved men­tal per­for­mance of school­child­ren in Benin”, van den Briel et al 2000; orig­i­nally a dou­ble-blind RCT, but sub­jects were con­t­a­m­i­nated by im­por­ta­tion of iodized salt (there was an ap­par­ent smal­l­-medium effect on the ma­trix sub­test)

  11. “Cog­ni­tive and mo­tor func­tions of iodine-d­e­fi­cient but eu­thy­roid chil­dren in Bangladesh do not ben­e­fit from iodized poppy seed oil (Li­p­i­odol)”, Huda et al 2001: 1st and 2nd grade chil­dren, ~1mg? no effect

  12. “In­flu­ence of sup­ple­men­tary vi­t­a­mins, min­er­als and es­sen­tial fatty acids on the an­ti­so­cial be­hav­iour of young adult pris­on­ers”, Gesch et al 2002: over 18 pris­on­ers, 0.14mg; ben­e­fi­cial effect on mea­sures of vi­o­lence, but they did not do an in­tel­li­gence retest and so are not use­ful for our pur­pose.

  13. “Effects of io­dine sup­ple­men­ta­tion dur­ing preg­nancy on child growth and de­vel­op­ment at school age”, O’­Don­nell 2002; in­cluded chil­dren who were sup­ple­mented at age 2 but only tested with Raven’s at age 7, which ren­ders their data not use­ful. How­ev­er, the gen­eral re­sults con­firm that tim­ing of sup­ple­men­ta­tion even within preg­nancy fol­lows the ‘ear­lier is bet­ter’ rule.

  14. “Io­dine sup­ple­men­ta­tion im­proves cog­ni­tion in iodine-d­e­fi­cient school­child­ren in Al­ba­nia”, Zim­mer­man et al 2006

  15. “Effect of mul­ti­vi­t­a­min and mul­ti­min­eral sup­ple­men­ta­tion on cog­ni­tive func­tion in men and women aged 65 years and over: a ran­domised con­trolled trial”, Mc­Neill et al 2007; old adults, 0.15mg; no effect

  16. “A mi­cronu­tri­en­t-for­ti­fied sea­son­ing pow­der re­duces mor­bid­ity and im­proves short­-term cog­ni­tive func­tion, but has no effect on an­thro­po­met­ric mea­sures in pri­mary school chil­dren in north­east Thai­land”, Manger et al 2008

  17. “De­layed Neu­robe­hav­ioral De­vel­op­ment in Chil­dren Born to Preg­nant Women with Mild Hy­pothy­rox­ine­mia Dur­ing the First Month of Ges­ta­tion: The Im­por­tance of Early Io­dine Sup­ple­men­ta­tion”, Berbel et al 2009; turns out that sup­ple­men­ta­tion was ad­min­is­tered to all women dur­ing their preg­nan­cy, so the de­vel­op­ment scores are not use­ful here.

  18. “Io­dine sup­ple­men­ta­tion im­proves cog­ni­tion in mildly iodine-d­e­fi­cient chil­dren”, Gor­don et al 2009

  19. think2 pro­ject:

  20. Dewi et al 2012, “Io­dine sup­ple­men­ta­tion into drink­ing wa­ter im­proved in­tel­li­gence of preschool chil­dren aged 25–59 months in Ngar­goyoso sub­-dis­trict, Cen­tral Java, In­done­sia: A ran­dom­ized con­trol trial”; sub­jects se­lected for low uri­nary io­dine ex­cre­tion, re­gion has >50% goi­ter rates

  21. van Stu­i­jven­berg et al 1999, “Effect of iron-, iodine-, and β-carotene -for­ti­fied bis­cuits on the mi­cronu­tri­ent sta­tus of pri­mary school chil­dren: a ran­dom­ized con­trolled trial”

  22. “Tim­ing of the Effect of Io­dine Sup­ple­men­ta­tion on In­tel­li­gence Quo­tients of School­child­ren”, Salarkia et al 2004; fol­lowup in 2 Iran­ian vil­lages after the na­tional in­sti­tu­tion of iodiza­tion in 1989

  23. Un­toro 1999, Use of Oral Iodized Oil to Con­trol Io­dine De­fi­ciency in In­done­sia, chap­ter 4 “Effect of stunt­ing, io­dine de­fi­ciency and oral iodized oil sup­ple­men­ta­tion on cog­ni­tive per­for­mance of school chil­dren in an en­demic io­dine de­fi­cient area of In­done­sia”, pg69–87

  24. Fier­ro-Benítez et al 1972 & Fier­ro-Benítez et al 1974, which are fol­lowups to the in­ter­ven­tion re­ported in Fier­ro-Benítez et al 1968 & (for a re­view of the Ecuado­rian ex­per­i­ments, see Greene 1994); a ground­break­ing se­ries of stud­ies be­gin­ning in the 1960s in which 8 goi­ter­ous vil­lages in Ecuador were treated with io­dine in­jec­tions and sub­se­quent long-term out­comes mea­sured through to the 1980s; for the most part, stud­ied chil­dren were affected pre­na­tally

  25. Gli­noer et al 1995, “A ran­dom­ized trial for the treat­ment of mild io­dine de­fi­ciency dur­ing preg­nan­cy: ma­ter­nal and neona­tal effects”: preg­nant women on­ly, no cog­ni­tive mea­sures

  26. Liesenkot­ter et al 1996, “Ear­li­est pre­ven­tion of en­demic goi­ter by io­dine sup­ple­men­ta­tion dur­ing preg­nancy”: ditto

  27. Nøhr et al 2000, “Post­par­tum thy­roid dys­func­tion in preg­nant thy­roid per­ox­i­dase an­ti­body-pos­i­tive women liv­ing in an area with mild to mod­er­ate io­dine de­fi­cien­cy: is io­dine sup­ple­men­ta­tion safe?”: ditto

  28. Ped­er­sen et al 1993, “Ame­lio­ra­tion of some preg­nan­cy-as­so­ci­ated vari­a­tions in thy­roid func­tion by io­dine sup­ple­men­ta­tion”: ditto

  29. Silva & Silva 1981, “In­ter­re­la­tion­ships among serum thy­rox­ine, tri­iodothy­ronine, re­verse tri­iodothy­ronine, and thy­roid-s­tim­u­lat­ing hor­mone in iodine-d­e­fi­cient preg­nant women and their off­spring: effects of io­dine sup­ple­men­ta­tion”: ditto

  30. Man­gani et al 2013, “Pro­vid­ing lipid-based nu­tri­ent sup­ple­ments does not affect de­vel­op­men­tal mile­stones among Malaw­ian chil­dren”: in­ter­ven­tion in­cluded io­dine (90mcg per 150g con­tain­er), but the de­vel­op­ment mile­stones are too differ­ent from IQ or cog­ni­tion to use for this

  31. San­ti­ago et al 2013, “In­fant neu­rocog­ni­tive de­vel­op­ment is in­de­pen­dent of the use of iodised salt or io­dine sup­ple­ments given dur­ing preg­nancy”: preg­nancy only

  32. Lavy et al 2015, “Out of Africa: Hu­man Cap­i­tal Con­se­quences of In Utero Con­di­tions”: an analy­sis of an in­trigu­ing , “”, in which 14k Ethiopi­ans (the en­tire Ethiopian Jew­ish com­mu­ni­ty) were over 2 days air­lifted from Ethiopia to Is­rael and set­tled there. Since a fair num­ber of the women were at vary­ing stages of preg­nan­cy, the abrupt­ness & com­pre­hen­sive­ness of the re­lo­ca­tion means that the causal effect of bet­ter Is­raeli pre­na­tal care can be in­ferred with­out any of the usual con­founders which would de­feat an at­tempt to com­pare Ethiopian school or test scores with Is­raeli. They find large effects, es­pe­cially for those air­lifted dur­ing the first trimester of preg­nancy & for fe­males (which is con­sis­tent with the run­ning theme of io­dine stud­ies: that the ben­e­fits are largest when done early dur­ing preg­nancy and larger for fe­males than males). Un­for­tu­nate­ly, it can’t be in­cluded as the de­sign is too differ­ent, noth­ing sim­i­lar to IQ tests were ad­min­is­tered, and the effects re­flect all the fac­tors en­tailed in mov­ing to Is­rael, which highly likely goes well be­yond just a mul­ti­vi­t­a­min.

  33. Sangün et al 2015, “The Effects of Six-Month L-Thy­rox­ine Treat­ment on Cog­ni­tive Func­tions and Even­t-Re­lated Brain Po­ten­tials in Chil­dren with Sub­clin­i­cal Hy­pothy­roidism”: non-ran­dom­ized

  34. Prado et al 2016, “Effects of ma­ter­nal and child lipid-based nu­tri­ent sup­ple­ments on in­fant de­vel­op­ment: a ran­dom­ized trial in Malawi”: ran­dom­ized, and in­cludes chil­dren 6–18­mo, but as­sessed only on de­vel­op­ment at 18­mo, which can’t be con­sid­ered a use­ful IQ test

  35. Li et al 2015, “Pre­na­tal Mi­cronu­tri­ent Sup­ple­men­ta­tion Is Not As­so­ci­ated with In­tel­lec­tual De­vel­op­ment of Young School-Aged Chil­dren”: 3 ex­per­i­men­tal groups: fo­late, fo­late+iron, folate+iron+others+150.0mg/d iodine, al­low­ing a com­par­i­son of fo­late with fo­late+­mul­ti­vi­t­a­m­in; but only pre­na­tal in­ter­ven­tion was done.

  36. Zahrou et al 2016, “For­ti­fied Io­dine Milk Im­proves Io­dine Sta­tus and Cog­ni­tive Abil­i­ties in School­child­ren Aged 7–9 Years Liv­ing in a Rural Moun­tain­ous Area of Mo­rocco” (fol­lowup to Zahrou et al 2015): rel­e­vant

  37. “A clus­ter-ran­dom­ized, con­trolled trial of nu­tri­tional sup­ple­men­ta­tion and pro­mo­tion of re­spon­sive par­ent­ing in Mada­gas­car: the MAHAY study de­sign and ra­tio­nale”, Fer­nald et al 2016: pre­reg­is­tra­tion of a study pro­to­col for a Mada­gas­car study; daily 90μg io­dine in the lipid-based T2/T3 arms vs T0/T1/T4 for chil­dren aged 6–18 months, de­vel­op­men­tal out­comes “Ages and Stages Ques­tion­naire: In­ven­tory” & “Bay­ley Scale” but no IQ test-ana­logue.

  38. “Effect of io­dine sup­ple­men­ta­tion dur­ing preg­nancy on thy­roid func­tion and cog­ni­tive de­vel­op­ment of off­spring”, Jaiswal (Ban­ga­lore In­di­a): preg­nant on­ly, no IQ tests

  39. Solon et al 2003, “Effect of a mul­ti­ple-mi­cronu­tri­en­t-for­ti­fied fruit pow­der bev­er­age on the nu­tri­tion sta­tus, phys­i­cal fit­ness, and cog­ni­tive per­for­mance of school­child­ren in the Philip­pines”: RCT in Philip­pine school-chil­dren (mean age 9.9); 4 groups to­tal (for­ti­fied sup­ple­ment x de­worm­ing), 10.8mg to­tal io­dine de­liv­ered over 16 weeks; Pri­mary Men­tal Abil­i­ties Test for Fil­ipino Chil­dren (PMAT-FC) used to mea­sure cog­ni­tive per­for­mance

  40. Lien et al 2009, “Im­pact of milk con­sump­tion on per­for­mance and health of pri­mary school chil­dren in rural Viet­nam”: claims cog­ni­tive ben­e­fits, es­pe­cially to short­-term mem­o­ry, but pa­per does not re­port quan­ti­ta­tive re­sults

  41. Prado et al 2016, “Effects of pre- and post-na­tal lipid-based nu­tri­ent sup­ple­ments on in­fant de­vel­op­ment in a ran­dom­ized trial in Ghana” & Adu-A­far­wuah et al 2016, : mea­sured “mo­tor, lan­guage, so­cio-e­mo­tion­al, and ex­ec­u­tive func­tion at 18 months” but too early for valid IQ tests, and the chil­dren ap­pear to have re­ceived sup­ple­men­ta­tion pre-na­tally

  42. Zhou et al, “The effect of io­dine sup­ple­men­ta­tion in preg­nancy on early child­hood neu­rode­vel­op­ment and clin­i­cal out­comes: re­sults of an aborted ran­domised place­bo-con­trolled trial”: preg­nancy only

  43. Pearce 2017, “Io­dine Sup­ple­men­ta­tion for Pre­ma­ture In­fants Does Not Im­prove IQ”: Bayley-III cog­ni­tive tests at age 2, no sta­tis­ti­cal­ly-sig­nifi­cant differ­ence or trend for the iodine-sup­ple­mented chil­dren (30mcg/kg/day for >3 weeks; pre­ma­ture in­fants can weigh any­where 0.5—2.5kg) . While the sup­ple­men­ta­tion is post-preg­nan­cy, pre­ma­ture in­fants are an un­usual enough pa­tient pop­u­la­tion (and one which fre­quently ) that it prob­a­bly is not a good idea to meta-an­a­lyze it with RCTs on nor­mal chil­dren & adults.

  44. Haas et al 2014/Wenger et al 2017, “Con­sump­tion of a Dou­ble-For­ti­fied Salt Affects Per­cep­tu­al, At­ten­tion­al, and Mnemonic Func­tion­ing in Women in a Ran­dom­ized Con­trolled Trial in In­dia”: RCT of iron+io­dine sup­ple­ment in 18–55yo, but where the con­trol also re­ceived iodized salt and the large ben­e­fits were due to re­duc­ing ane­mia

  45. , Ser­ena 2019; nat­ural ex­per­i­ment us­ing the Dan­ish gov­ern­men­t’s le­gal­iza­tion of and then re­quire­ment to iodize salt, 1998–2001, with a differ­ence-in-d­iffer­ences analy­sis sug­gest­ing d = 0.06 on affected ado­les­cents’ high school GPA. (Not a RCT, and differ­ence-in-d­iffer­ences are one of the weaker nat­ural ex­per­i­ment de­sign­s.)

My above searches & re­view turned out to be par­tially re­dun­dant with a re­view that was pub­lished on­line a few months after­wards, in June 2012: Zim­mer­man’s “The Effects of Io­dine De­fi­ciency in Preg­nancy and In­fancy” and also his ear­lier 2009 “Io­dine de­fi­ciency in preg­nancy and the effects of ma­ter­nal io­dine sup­ple­men­ta­tion on the off­spring: a re­view”. Re­gard­less, the above was still use­ful be­cause Zim­mer­man’s fo­cus was not on any child­hood or adult effects but the preg­nancy & in­fancy effects. I have also ben­e­fited from . Fi­nal­ly, “Im­pact of io­dine sup­ple­men­ta­tion in mild-to-mod­er­ate io­dine de­fi­cien­cy: sys­tem­atic re­view and meta-analy­sis” (Tay­lor et al 2014) re­views io­dine stud­ies and for cog­ni­tive per­for­mance, meta-an­a­lyzes Gor­don et al 2009 & Zim­mer­man et al 2009, find­ing ben­e­fits.

Un­for­tu­nate­ly, a few of the use­ful stud­ies also tested a va­ri­ety of sub­stances, so any es­ti­mate of iodine’s effect size (such as it is) would be an over­es­ti­mate: the io­dine might be syn­er­giz­ing with one of the other in­gre­di­ents (eg. iron or ) or the io­dine might not be the re­spon­si­ble agent at all! We will code that co­vari­ate in. But what im­pli­ca­tions can we draw out via a ?

Data

First, the data from the sur­viv­ing stud­ies:

study group year n.e mean.e sd.e n.c mean.c sd.c age dose multi coun­try
Bautista Bautista 1982 100 69.43 10.96 100 70.31 10.96 8.75 475 0 Bo­livia
Boy­ages Boy­ages 1990 28 34.4 15.4 24 29.5 8.5 29.5 720 0 China
Schoen­thaler.1 Schoen­thaler 1991 100 10.1 8.9 33.3 8.9 7.3 14 12.68 1 USA
Schoen­thaler.2 Schoen­thaler 1991 105 12.6 7.9 33.3 8.9 7.3 14 25.35 1 USA
Schoen­thaler.3 Schoen­thaler 1991 105 10.4 7.6 33.3 8.9 7.3 14 25.35 1 USA
Southon Southon 1994 22 63.94 2.6 29 64.1 1.87 13.5 16.8 1 UK
Shrestha.1 Shrestha 1994 72 17.1 1.8 36 10.7 2.4 7.1 490 0 Malawi
Shrestha.2 Shrestha 1994 80 18.2 1.5 36 10.7 2.4 7.1 490 0 Malawi
Isa Isa 2000 60 85.25 14.6 100 83.6 16.2 11.39 480 0 Malaysia
Huda Huda 2001 145 14.88 3.28 142 14.60 3.19 9.8 400 0 Bangladesh
Zim­mer­man Zim­mer­man 2006 159 25 6.3 151 20.5 5.6 11 400 0 Al­ba­nia
Mc­Neill Mc­Neill 2007 398 11.5 2.3 374 11.7 2.1 72 54.75 1 UK
Gor­don Gor­don 2009 84 10.2 3 82 9.6 2.4 11.5 29.4 0 NZ
Dewi Dewi 2012 33 110.27 9.04 34 103.06 9.99 3.1 8.4 0 In­done­sia
Salarkia Salarkia 2004 19 96 10 246 89 13 1.5 1272 0 Iran
Un­toro Un­toro 1999 121 89 7 43 88 6 9 464 0 In­done­sia
Red­man Red­man 2011 86 20.85 3.43 86 20.59 3.27 21.28 45 0 NZ
Solon Solon 2003 412 1.82 0.22 419 1.66 0.22 9.9 10.752 1 Philip­pines

Com­ments:

  1. “age” vari­able is based on a sim­ple av­er­age age in years of sub­jects (un­weight­ed) or the re­ported mean; “dose” is to­tal ad­min­is­tered io­dine in mil­ligrams (note that stud­ies typ­i­cally re­port in micrograms/μg per day or week); multi is whether the study used solely io­dine (0) or other chem­i­cals such as iron (1)

  2. Bautista notes: Stan­ford-Bi­net IQ, some data re-derived15

  3. Boy­ages: the two groups were not ran­domly cho­sen and may have pre-ex­ist­ing differ­ences in IQ

  4. Schoen­thaler: RAPM IQ

  5. Cao: an ear­lier ver­sion of this meta-analy­sis used its “de­vel­op­men­tal quo­tient” ex­clud­ing the preg­nant wom­en’s off­spring; since this does not seem to be IQ, I re­moved it

  6. Southon: Non-ver­bal IQ scores pooled16

  7. Mc­Neill: used in place of IQ scores (WM cor­re­lates highly with IQ)

  8. Gor­don: score from ma­trix sub­test (1 of 4 sub­test scores; 2 showed pos­i­tive trend but not sig­nifi­cance)

  9. Manger: ear­lier ver­sion used Manger’s back­wards digit span (back­wards is a WM test which loads on g); how­ev­er, the meta-analy­sis & my own found that WM ex­er­cises which trans­ferred to digit spans did not also trans­fer to IQ tests, rais­ing ques­tions about us­ing digit span as a proxy for IQ in a causal rather than cor­re­la­tional analy­sis

  10. Stu­i­jven­berg: see Manger

  11. Isa: IQ scores re­ported in un­help­ful for­mat; means & de­vi­a­tions re­verse-engi­neered from per­centile dis­tri­b­u­tion17; as usu­al, preg­nan­cy-re­lated scores are omit­ted

  12. Shrestha: ‘Fluid in­tel­li­gence’ scores re­port­ed, omit­ting ‘Crys­tal­lized in­tel­li­gence’ & ‘Per­cep­tual skill’; the con­trol group is split across the io­dine in­ter­ven­tion (“Shrestha.1”) and the iodine+­iron in­ter­ven­tion (“Shrestha.2”)

  13. Salarkia:

    1. the pa­per’s orig­i­nal con­trol group us­ing con­tem­po­rary age/sex-matched Tehran chil­dren, does­n’t ac­count for their su­pe­rior IQ scores and likely su­pe­rior SES; I have in­stead used the re­ported 1989 IQ scores of the pre­vi­ous gen­er­a­tion of chil­dren
    2. the ad­min­is­tered io­dine in­cludes the 480mg from iodized oil but also the 6 years of iodized salt con­sump­tion (40mg/kg, na­tional daily per capita av­er­age salt con­sump­tion 9g) or 132mg a year) for a to­tal of 1272mg
  14. Un­toro: there were 3 dose groups (200/400/800mg) but Un­toro re­ported sum­mary sta­tis­tics for the io­dine group as a whole:

    The uri­nary io­dine con­cen­tra­tion and thy­roid vol­ume of all treat­ment groups were [s­ta­tis­ti­cal­ly-]sig­nifi­cantly im­proved after the sup­ple­men­ta­tion, but there were no differ­ences among the sup­ple­mented groups in cog­ni­tive per­for­mance. There­fore we com­bined the three iodized oil sup­ple­mented groups into one group.

    The listed dose is a weighted av­er­age.

  15. Red­man: dose is cal­cu­lated as: 150 μg, 100 pills a bot­tle, 3 bot­tles (1 ini­tial bot­tle, 2 re­place­ments in mail) = = 45000μg; scores are from the Ma­trix Rea­son­ing sub­test

The re­sult of the meta-analy­sis:

Random-Effects Model (k = 17; tau^2 estimator: REML)

tau^2 (estimated amount of total heterogeneity): 1.2100 (SE = 0.4432)
tau (square root of estimated tau^2 value):      1.1000
I^2 (total heterogeneity / total variability):   97.87%
H^2 (total variability / sampling variability):  47.02

Test for Heterogeneity:
Q(df = 16) = 285.8785, p-val < .0001

Model Results:

estimate       se     zval     pval    ci.lb    ci.ub
  0.6204   0.2716   2.2844   0.0223   0.0881   1.1527
Test for Heterogeneity:
Q(df = 16) = 285.8785, p-val < .0001

Model Results:

estimate       se     zval     pval    ci.lb    ci.ub
  0.2565   0.0380   6.7536   <.0001   0.1820   0.3309

So the effect size is, as ex­pect­ed, small: d = 0.2. A far cry from the d > 1 which we might es­ti­mate from the pre­na­tal stud­ies.

The large differ­ence in d—0.2 vs 0.6—­be­tween the fixed-effects and ran­dom-effects mod­els is con­cern­ing. Given the ex­tremely high het­ero­gene­ity of the i2, which in­di­cates that there are large differ­ences be­tween some of the stud­ies, a ran­dom-effects is more ap­pro­pri­ate in prin­ci­ple; but fur­ther analy­sis shows this is be­ing dri­ven by a far out­lier of Shrestha, and so I be­lieve the fixed-effects es­ti­mate of 0.2 winds up be­ing more ac­cu­rate.

A pretty sum­ma­ry:

A for­est plot of io­dine stud­ies

Moderators

Age & dose

We sus­pect­ed, based on the equiv­o­cal re­sults in post-birth stud­ies and the large de­cline in effect over the du­ra­tion of a preg­nancy in the Chi­nese stud­ies, that if there was any ben­e­fit, it would be in the young; on the same rea­son­ing, we might ex­pect large doses to do more good than smaller ones. The nec­es­sary data is en­coded into the ta­ble al­ready, so we run a meta-an­a­lytic re­gres­sion on them as in­de­pen­dent pre­dic­tors:

tau^2 (estimated amount of residual heterogeneity):     1.2521 (SE = 0.4902)
tau (square root of estimated tau^2 value):             1.1190
I^2 (residual heterogeneity / unaccounted variability): 97.49%
H^2 (unaccounted variability / sampling variability):   39.92
R^2 (amount of heterogeneity accounted for):            0.00%

Test for Residual Heterogeneity:
QE(df = 14) = 243.6469, p-val < .0001

Test of Moderators (coefficient(s) 2,3):
QM(df = 2) = 1.6083, p-val = 0.4475

Model Results:

             estimate      se     zval    pval    ci.lb   ci.ub
intrcpt        0.6793  0.5205   1.3053  0.1918  -0.3407  1.6994
iodine$age    -0.0157  0.0183  -0.8568  0.3915  -0.0515  0.0202
iodine$dose    0.0006  0.0009   0.6665  0.5051  -0.0011  0.0023

The co­effi­cients and vari­abil­ity are dis­ap­point­ing: the age and dose mod­er­a­tors ex­plain lit­tle of what is go­ing on.

Some graphs to help us vi­su­al­ize. Graph­ing by age, we see what might be a slight neg­a­tive re­la­tion­ship, as the re­gres­sion sug­gests (driven by Shrestha 1994):

plot(iodine$age, effects$yi)

Graph­ing by dose, we see—de­spite the cal­cu­lated sig­nifi­cance—no re­la­tion­ship at all to my eyes (out­liers are Shrestha 1994, again):

plot(iodine$dose, effects$yi)

The estimate is the im­por­tant part: nei­ther of the mod­er­a­tors seem to have a strong re­la­tion­ship with the cog­ni­tive ben­e­fits (nor are they at least sta­tis­ti­cal­ly-sig­nifi­can­t). It would seem that any effec­tive­ness of io­dine is un­re­lated to age and dose. Whether the effec­tive­ness is be­ing dri­ven by a few stud­ies is what we’ll look at next.

Multiple supplements

One method­olog­i­cal con­cern is that by in­clud­ing stud­ies like Southon which sup­ple­mented many things be­sides iodine, our re­sults are merely pick­ing up the effi­cacy of other sup­ple­ments (iron is a par­tic­u­lar con­cern). Cu­ri­ous­ly, de­spite our ex­pec­ta­tion that the mul­ti­-vi­t­a­min stud­ies would have higher effect sizes be­cause any of the in­gre­di­ents could be help­ful singly or syn­er­gis­ti­cal­ly, it is strik­ingly the op­po­site:

QM(df = 2) = 6.7027, p-val = 0.0350

Model Results:

                       estimate      se    zval    pval    ci.lb   ci.ub
factor(iodine$multi)0    0.8250  0.3203  2.5756  0.0100   0.1972  1.4529
factor(iodine$multi)1    0.1300  0.4953  0.2625  0.7930  -0.8408  1.1008

Bias checks

We do not have enough to re­li­ably check for bi­ases like , but we can still try. The looks pretty bizarre, with al­most all stud­ies tightly bunched around the null effect but 2 out­lier­s—the 2 Shrestha 1994 groups we just saw—show­ing shock­ingly high effect sizes of d = 3.1/4.1. Why did Shrestha 1994 ob­serve such large IQ effects? I don’t know, al­though the Malawi re­gion was cho­sen for its io­dine de­fi­cien­cy.

A test & graph:

test for funnel plot asymmetry: z = 3.3206, p = 0.0009
A fun­nel plot of effect size ver­sus sam­ple size, check­ing for bias in pub­lish­ing only good-look­ing re­sults on io­dine

So Shrestha 1994 is dri­ving most of the effect! (Not a sur­prise at this point.) If we omit those points, the fun­nel plot is cleaner

A fun­nel plot with Shrestha re­moved, show­ing bet­ter fit from the weaker es­ti­mate.

A trim-and-fill check agrees with us and not the test, by de­cid­ing not to add in any new stud­ies be­tween Shrestha and the rest; we also no­tice that the τ2 & i2 are ex­tremely high, which is just telling us what we know—Shrestha 1994 is differ­ent from the other stud­ies:

Estimated number of missing studies on the left side: 0 (SE = NA)

Random-Effects Model (k = 17; tau^2 estimator: REML)

tau^2 (estimated amount of total heterogeneity): 1.2100 (SE = 0.4432)
tau (square root of estimated tau^2 value):      1.1000
I^2 (total heterogeneity / total variability):   97.87%
H^2 (total variability / sampling variability):  47.02

If we were to redo the analy­sis but omit­ting Shrestha 1994, we see a much smaller effec­t-size:

Random-Effects Model (k = 15; tau^2 estimator: REML)

tau^2 (estimated amount of total heterogeneity): 0.0526 (SE = 0.0313)
tau (square root of estimated tau^2 value):      0.2293
I^2 (total heterogeneity / total variability):   68.75%
H^2 (total variability / sampling variability):  3.20

Test for Heterogeneity:
Q(df = 14) = 53.0253, p-val < .0001

Model Results:

estimate       se     zval     pval    ci.lb    ci.ub
  0.2224   0.0751   2.9602   0.0031   0.0752   0.3697

So, it seems a lot of the effect size is be­ing dri­ven by a few stud­ies turn­ing in large or ex­tremely large effect sizes: Shrestha, Zim­mer­man, and Dewi (in chrono­log­i­cal or­der). One com­mon fac­tor to these stud­ies seems to be that they worked in the most iodine-de­prived ar­eas pos­si­ble: Shrestha chose his re­gion as be­ing the worst he could find, and Dewi cites re­ports of goi­ter in half the pop­u­la­tion while tar­get­ing the sup­ple­men­ta­tion to the most de­fi­cient chil­dren.

At most, we can jus­tify an effect es­ti­mate which is much smaller than would be es­ti­mated based on the pre­na­tal stud­ies, and the re­al­ity of this resid­ual effect can be doubt­ed: look­ing at the for­est plot, the more rig­or­ous and West­ern stud­ies seem to have the tini­est and clos­est to zero es­ti­mates.

Code

Run as R --slave --file=iodine.r:

set.seed(7777) # for reproducible numbers
# TODO: factor out common parts of `png` (& make less square), and `rma` calls
# install.packages("XML") # if not installed
library(XML)
iodine <- readHTMLTable(colClasses = c("character", "integer", rep("numeric", 8)),
                     "https://www.gwern.net#data")[[1]]
# install.packages("metafor") # if not installed
library(metafor)

effects <- escalc("SMD", m1i = mean.e, m2i = mean.c, sd1i = sd.e, sd2i = sd.c, n1i = n.e, n2i = n.c,
                  data = iodine)

cat("Basic random-effects meta-analysis of all studies:\n")
res1 <- rma(yi, vi, data = effects); res1

cat("Fixed-effects version:\n")
res2 <- rma(yi, vi, data = effects, method="FE"); res2

png(file="~/wiki/images/iodine/forest.png", width = 480, height = 480)
forest(res1, slab = paste(iodine$study, iodine$year, sep = ", "))
invisible(dev.off())

cat("Random-effects with age & dose moderators:\n")
rma(yi, vi, mods = ~ iodine$age + iodine$dose, data = effects)

png(file="~/wiki/images/iodine/age.png", width = 480, height = 480)
plot(iodine$age, effects$yi)
invisible(dev.off())

png(file="~/wiki/images/iodine/dose.png", width = 480, height = 480)
plot(iodine$dose, effects$yi)
invisible(dev.off())

cat("Check random-effects meta-analysis for whether the multiple-supplement trials are inflating results:\n")
rma(yi, vi, mods = ~ factor(iodine$multi) - 1, data = effects)

png(file="~/wiki/images/iodine/funnel.png", width = 480, height = 480)
funnel(res1)
invisible(dev.off())

cat("The funnel plot looks weird, test it:\n")
regtest(res1, model = "rma", predictor = "sei", ni = NULL)

cat("For kicks, what does a (normal) trim-and-fill say?\n")
tf <- trimfill(res1); tf

cat("Re-run random-effects meta-analysis, omitting Shrestha:\n")
res3 <- rma(yi, vi, data = escalc("SMD", m1i = mean.e, m2i = mean.c, sd1i = sd.e, sd2i = sd.c,
                                  n1i = n.e, n2i = n.c,
                                  data = iodine[!(grepl("Shrestha", iodine$study)),])); res3

# funnel plot with Shrestha omitted
png(file="~/wiki/images/iodine/funnel-moderated.png", width = 480, height = 480)
funnel(res3)
invisible(dev.off())

# optimize the generated graphs by cropping whitespace & losslessly compressing them
system(paste('cd ~/wiki/images/iodine/ &&',
             'for f in *.png; do convert "$f" -crop',
             '`nice convert "$f" -virtual-pixel edge -blur 0x5 -fuzz 10% -trim -format',
             '\'%wx%h%O\' info:` +repage "$f"; done'))
system("optipng -o9 -fix ~/wiki/images/iodine/*.png", ignore.stdout = TRUE)

See Also

  • Io­dine sec­tion of Nootrop­ics es­say -(­mo­ti­va­tion; some sta­tis­ti­cal power cal­cu­la­tions for a self­-ex­per­i­ment look­ing for cog­ni­tive im­prove­ment; a “value of in­for­ma­tion” cal­cu­la­tion on the pos­si­ble ben­e­fit ver­sus the qual­ity of in­for­ma­tion from self­-ex­per­i­ment­ing; a silly eye­-color ex­per­i­ment re­sult­ing in no change from sup­ple­men­ta­tion)

  1. See Scrimshaw 1998; Ble­ichrodt & Born 1994; and Qian et al 2005:

    Thir­ty-seven re­ported stud­ies, to­tal 12,291 chil­dren, were analysed. The effect size was an in­crease of 0.83, 0.82, and 0.32 SIQP re­spec­tive­ly, for the chil­dren liv­ing in IS com­mu­ni­ties com­pared with those liv­ing in ID ar­eas with no io­dine sup­ple­men­ta­tion, with in­ad­e­quate io­dine sup­ple­men­ta­tion, or chil­dren who had re­ceived io­dine dur­ing their moth­ers’ preg­nancy and after birth. These equal to 12.45, 12.3, 4.8 IQ points. Com­pared with that of chil­dren whose moth­ers were per­sis­tently ex­posed to ID, the to­tal effect size of the 21 en­tries was an in­crease of 0.58 SIQP (8.7 IQ points) in the group re­ceiv­ing io­dine sup­ple­men­ta­tion dur­ing preg­nan­cy. Fur­ther­more, there was an in­crease on 1.15 SIQP of Bi­net or 0.8 SIQP on Raven Scale (17.25 or 12 IQ points) for chil­dren born more than 3.5 years after io­dine sup­ple­men­ta­tion pro­gram was in­tro­duced. The level of io­dine nu­tri­tion plays a cru­cial role in the in­tel­lec­tual de­vel­op­ment of chil­dren. The in­tel­li­gence dam­age of chil­dren ex­posed to se­vere ID was pro­found, demon­strated by 12.45 IQ points loss and they re­cov­ered 8.7 IQ points with io­dine sup­ple­men­ta­tion or IS be­fore and dur­ing preg­nancy

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  2. , Jones 2006:

    In a re­cently pub­lished pa­per, Er­ica Field, Omar Rob­les, and Max­imo Torero study the effects of io­dine de­fi­ciency on ed­u­ca­tional at­tain­ment in Tan­za­nia (Field, Rob­les and Torero 2009). Theirs is the first pub­lished pa­per to link eco­nom­i­cally [im­por­tant] out­comes to io­dine de­fi­cien­cy, and it sup­ports the idea of im­proved school­ing out­comes after io­dine sup­ple­men­ta­tion. In­ter­est­ing­ly, Field et al. also find big­ger effects for fe­males, which could be due ei­ther to bi­o­log­i­cal differ­ences or differ­ences as­so­ci­ated with in­tra-house­hold re­source al­lo­ca­tion and so­cial re­sponses to in­creased cog­ni­tion of males and fe­males.

    The orig­i­nal:

    Our find­ings sug­gest that re­duc­ing fe­tal IDD has [sub­stan­tial] ben­e­fits for child cog­ni­tion: Chil­dren who re­ceive io­dine in utero at­tain an av­er­age of 0.33 years of ed­u­ca­tion above sib­lings and older and younger chil­dren in their dis­trict. Fur­ther­more, the effects ap­pear to be sub­stan­tially larger for girls, con­sis­tent with new ev­i­dence from lab­o­ra­tory stud­ies in an­i­mals in­di­cat­ing greater cog­ni­tive sen­si­tiv­ity of the fe­male fe­tus to in utero io­dine de­pri­va­tion, in­clud­ing sex-spe­cific re­sponses to ma­ter­nal thy­roid hor­mone re­stric­tion on ex­pres­sion of neural thy­roid hor­mone re­cep­tors. The re­sults are con­sis­tent across house­hold and dis­trict fixed effects mod­els and pat­terns of vari­a­tion in es­ti­mated effects are con­sis­tent with pre­dic­tions re­gard­ing the vul­ner­a­bil­ity of spe­cific sub­pop­u­la­tions to fe­tal IDD. Cross-coun­try re­gres­sion es­ti­mates in­di­cate a strong neg­a­tive in­flu­ence of to­tal goi­ter rate and strong pos­i­tive in­flu­ence of salt iodiza­tion on fe­male school par­tic­i­pa­tion.

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  3. An ex­am­ple of the com­mer­cial op­po­si­tion or con­spir­acy the­o­rists is the Kaza­khstan cam­paign; from “In Rais­ing the World’s I.Q., the Se­cret’s in the Salt”, NYT:

    In fact, Kaza­khstan has be­come an ex­am­ple of how even a vast and stil­l-de­vel­op­ing na­tion like this Cen­tral Asian coun­try can achieve a re­mark­able pub­lic health suc­cess. In 1999, only 29% of its house­holds were us­ing iodized salt. Now, 94% are. Next year, the United Na­tions is ex­pected to cer­tify it offi­cially free of io­dine de­fi­ciency dis­or­der­s…Largely out of the pub­lic eye, they made ter­rific pro­gress: 25% of the world’s house­holds con­sumed iodized salt in 1990. Now, about 66% do.

    …In some na­tions, iodiza­tion be­comes tarred as a gov­ern­ment plot to poi­son an es­sen­tial of life—salt ex­perts com­pare it to the fu­ri­ous op­po­si­tion by 1950s con­ser­v­a­tives to flu­o­ri­da­tion of Amer­i­can wa­ter. In oth­ers, civil lib­er­tar­i­ans de­mand a right to choose plain salt, with the re­sult that the iodized kind rarely reaches the poor. Small salt mak­ers who fear ex­tra ex­pense often lobby against it. So do mak­ers of io­dine pills who fear los­ing their mar­ket. Ru­mors in­evitably swirl: io­dine has been blamed for AIDS, di­a­betes, seizures, im­po­tence and peev­ish­ness. Iodized salt, ac­cord­ing to differ­ent na­tional ru­mor mills, will make pick­led veg­eta­bles ex­plode, ruin caviar or soften hard cheese. Break­ing down that re­sis­tance takes both money and lead­er­ship…The coun­try’s biggest salt com­pany was ini­tially re­luc­tant to co­op­er­ate, fear­ing higher costs, a Unicef re­port said. Car­di­ol­o­gists ar­gued against iodiza­tion, fear­ing it would en­cour­age peo­ple to use more salt, which can raise blood pres­sure. More in­sid­i­ous, Dr. Shar­manov said, were pri­vate com­pa­nies that sold io­dine pills. “They pro­moted their prod­ucts in the mass me­dia, say­ing iodized salt was dan­ger­ous,” he said, shak­ing his head­…Asked about the Unicef re­port say­ing that Aral Tuz ini­tially re­sisted iodiza­tion on the grounds that it would eat up 7% of profits, the com­pa­ny’s pres­i­dent, On­ta­lap Akhme­tov, seemed puz­zled. “I’ve only been pres­i­dent three years,” he said. “But that makes no sense.” The ex­pense, he said, was min­i­mal. “Only a few cents a ton.”

    …In the 1990s, when the cam­paign for iodiza­tion be­gan, the world’s great­est con­cen­tra­tion of iodine-d­e­fi­cient coun­tries was in the land­locked for­mer So­viet re­publics of Cen­tral Asia. All of them—Kaza­khstan, Turk­menistan, Tajik­istan, Uzbek­istan, Kyr­gyzs­tan—­saw their economies break down with the col­lapse of the So­viet Union. Across the re­gion, only 28% of all house­holds used iodized salt. “With the col­lapse of the sys­tem, cer­tain ba­bies went out with the bath­wa­ter, and iodiza­tion was one of them,” said Alexan­dre Zouev, chief Unicef rep­re­sen­ta­tive in Kaza­khstan…That com­bi­na­tion is miss­ing in many na­tions where io­dine de­fi­ciency re­mains a health cri­sis. In nearby Pak­istan, for in­stance, where 70% of house­holds have no iodized salt, there are more than 600 small salt pro­duc­ers. [see “Pak­istan takes le­gal ac­tion”, Unicef; for fur­ther read­ing, the WHO’s As­sess­ment of io­dine de­fi­ciency dis­or­ders and mon­i­tor­ing their elim­i­na­tion]

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  4. av­er­age daily Japan­ese con­sump­tion of io­dine ranges from 5.28-13.8mg of iodine; Patrick L. Iodine: de­fi­ciency and ther­a­peu­tic con­sid­er­a­tions, al­though Gaby ar­gues this is a mis­in­ter­pre­ta­tion: “the idea that Japan­ese peo­ple con­sume 13.8 mg of io­dine per day ap­pears to have arisen from a mis­in­ter­pre­ta­tion of a pa­per. In that pa­per, the av­er­age in­take of sea­weed in Japan was listed as 4.6 g (4,600 mg) per day, and sea­weed was said to con­tain 0.3% io­dine. The fig­ure of 13.8 mg comes from mul­ti­ply­ing 4,600 mg by 0.003. How­ev­er, the 4.6 g of sea­weed con­sumed per day was ex­pressed as wet weight, whereas the 0.3%-io­dine fig­ure based on dry weight. Since many veg­eta­bles con­tain at least 90% wa­ter, 13.8 mg per day is a [large] over­es­ti­mate of io­dine in­take. In stud­ies that have specifi­cally looked at io­dine in­take among Japan­ese peo­ple, the mean di­etary in­take (es­ti­mated from uri­nary io­dine ex­cre­tion) was in the range of 330 to 500 mcg per day, which is at least 2.5-fold lower than 13.8 mg per day.” Abra­ham replies “The uri­nary ex­cre­tions of io­dide re­ported by Ishizuki et al in ref­er­ences 7 and 8 of Gaby’s ed­i­to­r­ial are ob­vi­ously from pa­tients who were told to ab­stain from sea­weed. We will quote other stud­ies by Japan­ese in­ves­ti­ga­tors who re­ported uri­nary io­dide lev­els 10 to 100 time higher than the val­ues re­ported by Ishizuki et al .”↩︎

  5. , Politi 2014 (see also Field et al 2009):

    I iden­tify the im­pact of iodiza­tion in three ways: first, in a differ­ences-in-d­iffer­ences frame­work, I ex­ploit ge­o­graphic vari­a­tion in io­dine de­fi­cien­cy, as well as the fact that the na­tion­wide cam­paign to de­crease io­dine de­fi­ciency be­gan in 1922. Sec­ond, I use spa­tial and tem­po­ral vari­a­tion in the in­tro­duc­tion of iodized salt across Swiss can­tons, and ex­am­ine whether the level of iodized salt sales at the time of one’s birth affected one’s ed­u­ca­tional at­tain­ment. Third, I em­ploy a fuzzy re­gres­sion dis­con­ti­nu­ity de­sign and use jumps in sales of iodized salt across Swiss can­tons to iden­tify the effect of iodiza­tion, by com­par­ing out­comes for those born right be­fore and right after these sud­den changes in the treat­ment en­vi­ron­ment. These ap­proaches in­di­cate that the erad­i­ca­tion of io­dine de­fi­ciency in pre­vi­ously de­fi­cient ar­eas in­creased the school­ing of the pop­u­la­tion [s­ta­tis­ti­cal­ly-]sig­nifi­cant­ly. The effects are larger for fe­males than for males, which is con­sis­tent with med­ical ev­i­dence show­ing that women are more likely to be affected by io­dine de­fi­ciency dis­or­ders than men.

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  6. “Salt Iodiza­tion and the En­fran­chise­ment of the Amer­i­can Worker”, Ad­hvaryu et al 2013:

    …We find sub­stan­tial im­pacts of salt iodiza­tion. High school com­ple­tion rose by 6 per­cent­age points, and la­bor force par­tic­i­pa­tion went up by 1 point. Analy­sis of in­come tran­si­tions by quan­tile shows that the new la­bor force join­ers en­tered at the bot­tom of the wage dis­tri­b­u­tion and took up blue col­lar labor, pulling down av­er­age wage in­come con­di­tional on em­ploy­ment. Our re­sults in­form the on­go­ing de­bate on salt iodiza­tion in many low-in­come coun­tries. We show that large-s­cale iodized salt dis­tri­b­u­tion had a tar­geted im­pact, ben­e­fit­ing the worker on the mar­gin of em­ploy­ment, and gen­er­at­ing size­able eco­nomic re­turns at low cost.

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  7. Politi 2015, ↩︎

  8. “The Eco­nomic Effects of Mi­cronu­tri­ent De­fi­cien­cy: Ev­i­dence from Salt Iodiza­tion in the United States”, Feyrer et al 2008 (quotes are from 2008 draft, not 2013 fi­nal ver­sion):

    For in­stance, Sachs (2003) shows that efforts to elim­i­nate malaria have sub­stan­tial effects on in­come, through their effect on health, re­duced ab­sen­teeism, etc. Ace­moglu and John­son (2007) look at the effect of health in­ter­ven­tions and find lit­tle effect. Weil (2007) charts a mid­dle course…­For ex­am­ple, Bleak­ley (2007) ex­am­ines the effects of hook­worm erad­i­ca­tion in the Amer­i­can South in early 20th cen­tury and finds [sub­stan­tial] effects on ed­u­ca­tion and fu­ture in­comes of those co­horts that ben­e­fited from the in­ter­ven­tion.

    …Fig­ure 1 il­lus­trates the ge­o­graphic dis­tri­b­u­tion of goi­ter in the US as mea­sured among World War I re­cruits (we dis­cuss the data fur­ther be­low). In 1924 iodized salt was in­tro­duced in the United States ex­plic­itly to re­duce the goi­ter rate. This in­ter­ven­tion rapidly re­duced the in­ci­dence of io­dine de­fi­cien­cy. Iodiza­tion of salt in the US pro­vides a par­tic­u­larly good nat­ural ex­per­i­ment due to the ge­o­graphic dis­tri­b­u­tion of the dis­ease com­bined with a rapid, com­plete treat­ment. Since there are large in utero effects of io­dine de­fi­cien­cy, we should see a [sub­stan­tial] differ­ence be­tween those born be­fore and after the in­tro­duc­tion of iodized salt in lo­ca­tions with low lev­els of en­vi­ron­men­tal io­dine. Those liv­ing in high io­dine re­gions pro­vide a con­trol group…The prob­a­bil­ity of as­sign­ment to the Air Corps rises [sub­stan­tial­ly] in low io­dine (i.e. high goi­ter) coun­ties in the years after the in­tro­duc­tion of iodized salt. In the low­est io­dine re­gions, our es­ti­mates sug­gest a 10–20% in­crease in the prob­a­bil­ity of a man be­ing as­signed to the Air Corps after iodiza­tion. Us­ing in­for­ma­tion about av­er­age scores of Air and Ground Force re­cruits we can in­fer a one-quar­ter to one half stan­dard de­vi­a­tion in­crease in av­er­age test scores in these re­gions. The av­er­age level of io­dine de­fi­ciency in the US was [sub­stan­tial­ly] lower than in the high­est re­gions, so the over­all effect in the US was much more mod­est, though iodiza­tion was un­doubt­edly ex­tremely cost effec­tive. The in­crease in cog­ni­tive abil­ity due to salt iodiza­tion may have con­tributed a small amount to trend rise in mea­sured IQ that took place over the course of the twen­ti­eth cen­tu­ry, the so-called Behrman and Rosen­zweig (2004) find that differ­ences in birth weight among iden­ti­cal twins are re­flected in differ­ences in school at­tain­ment and adult earn­ings…­More cites to be added, in­clud­ing Case & Pax­son.

    Typ­i­cal­ly, non-d­e­fi­cient pop­u­la­tions differ from iodine-d­e­fi­cient pop­u­la­tions by ap­prox­i­mately 10 IQ points, whereas the whole nor­mal IQ dis­tri­b­u­tion of a pop­u­la­tion shifts to the left as a re­sult of io­dine de­fi­ciency7. In en­demic ar­eas, cre­tinism can affect up to 15% of the pop­u­la­tion (de Benoist et al., eds 2004). Ble­ichrodt and Born (1994) es­ti­mate that the av­er­age IQ of iodine-d­e­fi­cient groups is 13.5 points lower than the non-d­e­fi­cient groups…Scrimshaw (1998) pro­vides a list of stud­ies and ex­per­i­ments that have been con­duct­ed, and which have shown the hin­der­ing effects on men­tal de­vel­op­ment of io­dine de­fi­ciency in utero.

    …It had been doc­u­mented that large amounts of io­dine could cause hy­per­thy­roidism to de­velop in some adults and in oth­er­s…thy­ro­tox­i­co­sis might oc­cur as a re­sult of iodiza­tion in those in­di­vid­u­als that have suffered from long-term io­dine de­fi­ciency and whose goi­ters have be­come nodu­lar. In such cas­es, io­dine sup­ple­men­ta­tion causes the out­put of hor­mone to jump to toxic lev­el­s…The num­ber of en­listed men started in­creas­ing in 1942, and it peaked in the sec­ond se­mes­ter of that year, as well as the first se­mes­ter of 1943. Peo­ple born after iodiza­tion en­listed in large num­bers start­ing the first se­mes­ter of 1943. The pro­por­tion of re­cruits go­ing to the Air Force was par­tic­u­larly low in 1943…How large are these effects? The high­est goi­ter places have goi­ter rates of 30. The co­effi­cients (from Ta­ble 4) sug­gest that about 15% more re­cruits from the high­est goi­ter re­gions go into the AAF after salt iodiza­tion. From Ap­pen­dix A we know that the Air Force re­cruits have, on av­er­age 9 point higher AGCT scores (al­most a half a stan­dard de­vi­a­tion). The av­er­age in­crease for the re­cruits from that sec­tion is there­fore 0.15 time 9 points, or 1.35. So the av­er­age cog­ni­tive abil­ity in the sec­tion goes up by greater than one twen­ti­eth of a stan­dard de­vi­a­tion. Ex­am­in­ing the high­-low re­gres­sions yields sim­i­lar fig­ures. In the high goi­ter group, we have a 5–10% higher as­sign­ment rate to the AAF after salt iodiza­tion. 10% times 8 AGCT points re­sults in 0.8 points higher on av­er­age, or about a twen­ti­eth of a stan­dard de­vi­a­tion. This im­plies a twen­ti­eth of a stan­dard de­vi­a­tion in­crease in cog­ni­tive abil­ity for 25% of the US pop­u­la­tion.

    The fi­nal ver­sion finds a more sub­stan­tial effect:

    The es­ti­mated co­effi­cient on the high­-goi­ter dummy in ta­ble 5 is in the range 2.5–8.7 per­cent­age points. Sim­i­lar­ly, the logit spec­i­fi­ca­tion in Ta­ble 8 im­plies a mar­ginal effect of iodiza­tion on the prob­a­bil­ity of en­ter­ing the AAF in the range of 3–7.8 per­cent­age points. Com­par­ing these es­ti­mates to Ta­ble 9, we see that the lower range of these es­ti­mates are con­sis­tent with iodiza­tion rais­ing IQ by 15 points (that is, X = 15), which is a rea­son­able ex­pec­ta­tion given the work of (Ble­ichrodt and Born 1994). How­ev­er, the higher range of es­ti­mates is larger than any rea­son­able es­ti­mate of the in­crease in IQ that would have re­sulted from iodiza­tion. Given the un­cer­tainty sur­round­ing the se­lec­tion process and prior lit­er­a­ture on iodiza­tion we do not con­sider the larger re­sults plau­si­ble. In any case, our re­sults are con­sis­tent with a sub­stan­tial effect in line with the ex­ist­ing lit­er­a­ture.

    But un­for­tu­nate­ly, the de­tailed mech­a­nisms & psy­cho­met­rics are in­suffi­cient to sup­port a con­crete es­ti­mate of IQ gains, as taken lit­er­al­ly, their re­sults in­di­cate an IQ gain some­where around 30 points; this is suffi­ciently large as to prove that the analy­sis is not fully cap­tur­ing the dy­nam­ics and the es­ti­mates can­not be taken lit­er­ally aside from prov­ing that there was prob­a­bly a sub­stan­tial gain. (Based on the many prob­lems with the iodiza­tion lit­er­a­ture, sug­gest­ing 15 points is prob­a­bly an over­es­ti­mate.)

    An­other in­ter­est­ing pa­per ex­ploits the sim­i­larly abrupt in­tro­duc­tion of iron for­ti­fi­ca­tion into the USA ~WWII: “Iron­ing Out De­fi­cien­cies: Ev­i­dence from the United States on the Eco­nomic Effects of Iron De­fi­ciency”, Niemesh 2015.↩︎

  9. “Effects of drink­ing wa­ter with high io­dine con­cen­tra­tion on the in­tel­li­gence of chil­dren in Tian­jin, China” (slides), Liu et al 2009:

    The re­sults in­di­cated that for chil­dren who resided in re­gions with a very high wa­ter io­dine con­cen­tra­tion, there was on av­er­age a re­duc­tion of IQ by nearly nine points (b = −8.7, 95% CI: −15.9 to −1.4) in com­par­i­son with those who resided in a non-high wa­ter io­dine area. When com­par­ing chil­dren liv­ing in ar­eas with a high wa­ter io­dine con­cen­tra­tion with those in the non-high ar­eas, a slight re­duc­tion of IQ by about two points was ob­served, how­ev­er, it was not [s­ta­tis­ti­cal­ly-]sig­nifi­cant. There was also a [s­ta­tis­ti­cal­ly-]sig­nifi­cant as­so­ci­a­tion be­tween year of birth and IQ, which seemed to ex­hibit a dose-re­sponse re­la­tion­ship. There was a pro­gres­sive in­crease in IQ by about four (p = 0.072) and eight (p = 0.015) points for chil­dren born in 1996 and 1997 when com­pared with those who were born in 1995, the year China first im­ple­mented the na­tional di­etary io­dine sup­ple­ment pro­gramme.

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  10. An­a­lyzed 88 sam­ples; 47 fell be­low USFDA rec­om­mended level and their la­beled lev­el: Das­gupta PK, Liu Y, Dyke JV. “Io­dine nu­tri­tion: io­dine con­tent of iodized salt in the United States”↩︎

  11. Salt in cook­ing meat loses ~60% of iodine; Wang et al 1999, Effects of stor­age and cook­ing on the io­dine con­tent in iodized salt and study on mon­i­tor­ing io­dine con­tent in iodized salt↩︎

  12. “Io­dine sta­tus of UK school­girls: a cross-sec­tional sur­vey”, Van­der­pump et al 2011; see also “The preva­lence of io­dine de­fi­ciency in women of re­pro­duc­tive age in the United States of Amer­ica”, Hol­low­ell et al 2007↩︎

  13. Gun­ton JE, Hams G, Fiegert M, McEl­duff A. Io­dine de­fi­ciency in am­bu­la­tory par­tic­i­pants at a Syd­ney teach­ing hos­pi­tal: is Aus­tralia truly io­dine re­plete?; see also .↩︎

  14. Hop­tion Cann SA. “Hy­poth­e­sis: di­etary io­dine in­take in the eti­ol­ogy of car­dio­vas­cu­lar dis­ease”:

    In the gen­eral United States (US) pop­u­la­tion, a de­clin­ing trend in uri­nary io­dine lev­els has been ob­served as es­ti­mated through the large Na­tional Health and Nu­tri­tion Ex­am­i­na­tion Sur­veys (NHANES I, 1971–74; and NHANES III, 1988–94) [3]. The pro­por­tion of the US pop­u­la­tion with mod­er­ate to se­vere io­dine de­fi­ciency (<50 μg iodine/L in urine) has more than quadru­pled in the last 20 years, 2.6% in NHANES I vs 11.7% in NHANES III [3]. This de­cline may be due to a re­duced in­take of iodized salt. For ex­am­ple, En­strom et al. [4] com­pared data from na­tion­ally rep­re­sen­ta­tive sam­ples of the Amer­i­can pop­u­la­tion from two time pe­ri­ods, 1980–1982 vs 1990–1992. Based on di­etary in­take stud­ies from over 10,000 in­di­vid­u­als, no change was ob­served in sodium in­take from food, while there was a 65% de­cline in sodium in­take from dis­cre­tionary (iodized) salt. Ad­ven­ti­tious sources of io­dine have also de­clined with re­duc­tions in the use of io­dine in the dairy in­dus­try and in com­mer­cial bread pro­duc­tion [5]. Com­pa­ra­ble trends have been ob­served in other coun­tries that iodize salt. For ex­am­ple, pub­lic health rec­om­men­da­tions to re­duce salt in­take have been im­pli­cated in the de­creas­ing io­dine sta­tus in Aus­tralia and New Zealand [6]. Sim­i­lar­ly, a re­cent de­cline in me­dian uri­nary io­dine lev­els in Aus­tria may be due to lower salt in­take as well as the avail­abil­ity of non­iodized salt in Aus­tria after join­ing the Eu­ro­pean Union in 1995 [7]. In Green­land, as im­ported foods have re­placed con­sump­tion of tra­di­tional foods such as fish and sea mam­mals, there has been a grad­ual de­cline in io­dine sta­tus. An­der­sen et al. [8] found that me­dian uri­nary io­dine ex­cre­tion de­clined with the de­gree of de­crease in the tra­di­tional lifestyle. Ev­i­dence of io­dine de­fi­ciency was seen in non-I­nuit sub­jects, who had the low­est lev­els. Thus, in coun­tries where there are chang­ing di­etary pat­terns, in­clud­ing those long es­tab­lished iodiza­tion pro­grams, [sub­stan­tial] de­clines in io­dine in­take may oc­cur.

    See also Cald­well et al 2005; Pearce et al 2004; Trumpff et al 2013; and Gahche et al 2013↩︎

  15. Bautista did not re­port stan­dard de­vi­a­tions, but did re­port _n_s, means, and p-val­ues, which per­mits the stan­dard de­vi­a­tion to be de­rived, fol­low­ing the Cochrane Hand­book (“7.7.3.3 Ob­tain­ing stan­dard de­vi­a­tions from stan­dard er­rors, con­fi­dence in­ter­vals, t val­ues and p val­ues for differ­ences in means”): the de­grees of free­dom = 198, so with a re­ported p = 0.57, t = 0.569; then the stan­dard er­ror is the means di­vided by the t value (); and fi­nally the stan­dard de­vi­a­tion: .↩︎

  16. Southon re­ported con­trol & ex­per­i­men­tal scores split by gen­der, which need to be re-pooled:

    • con­trol

      1. mean =
      2. stan­dard de­vi­a­tion =
    • ac­tive

      1. mean =
      2. stan­dard de­vi­a­tion =
    ↩︎
  17. See Ta­ble 7; 12 month fol­lowup scores are re­ported grouped in IQ deciles, and if one as­sumes scores in each decile av­er­age to around the me­dian (s­ince they should be fol­low­ing a bell curve, this will over­state stan­dard de­vi­a­tion­s), one can cal­cu­late out the fig­ures in R as fol­lows:

    # experimental
    sd(c(rep(65,12), rep(75,10), rep(85,17), rep(100,19), rep(115,1), rep(125,1), rep(135,0)))
    [1] 14.59699
    mean(c(rep(65,12), rep(75,10), rep(85,17), rep(100,19), rep(115,1), rep(125,1), rep(135,0)))
    [1] 85.25
    
    # control
    sd(c(rep(65,30), rep(75,13), rep(85,25), rep(100,26), rep(115,5), rep(125,0), rep(135,1)))
    [1] 16.19141
    mean(c(rep(65,30), rep(75,13), rep(85,25), rep(100,26), rep(115,5), rep(125,0), rep(135,1)))
    [1] 83.6
    ↩︎