Effect of dietary iodine on serum inorganic and salivary iodine

Effect of Dietary Iodine on Serum Inorganic and Salivary Iodine R. L. VOUGHT

By

Th e quantitative relationships of the concentration of inorganic iodine (112’) in serum (SII) and salivary iodine concentration with the dietary iodine intake were studied in 4 normal women living at home and following their usual diehabits. tary, work, and recreational LTnder these conditions SII was found to he directly proportional to the dietary iodine intake on the day the blood sample was obtained. Salivary iodine concentrations and salivary iodine secre-

T

HE

QUANTITATIVE

inorganic

iodine

I\'. T. LO~YI~O~

AND

tion rates were also directly proportional to iodine intake, but the proportionality was linear only at intake levels below 167 pg./day. In addition, SII, salivary iodine concentrations, salivary iodine secretion rates, and salivary protein bound iodine concentrations were determined in 19 subjects during a s-week period. The frequency distributions of these 4 parameters proved to be lognormal. The implications of the data are discussed.

RELATIONSHIP

( I1”i)

between

the

concentration

ot

in blood

and dietary iodine intake has not been established; and, although the salivary glands are known to concentrate plasma iodide, the relationship of salivary iodine to dietary iodine or to the level of plasma (or serum) inorganic iodine ( SII) * is also not known. This

paper

reports

these relationships

as found

during

10 days observations

of 1

persons living at home and following their usual dietary, work, and r(‘c’reational habits. Under these conditions, SII ~1s found to be directlv proportional to the dietary iodine intake on the day the blood sample &s OIItained. Salivary iodine concentrations ( ST1 ) ant1 salivary iodine secretiotl rates (SSR) were also directly proportional to iodine intake, bllt the proportionality was linear only at lower levels of intake. In addition, SII, STI, SSR and salivary protein hormd (SPRI ) iodine wcr(’ determined

in 19 subjects

of these 4 parameters

during

proved

a 5-week

period.

The frequcncv

distrihlltion

to be lognormal.

MATERIALS

AND

METHODS

I>ata for this report were collected during :I study of iodine ink&e autl excretion in a group of 5 families comprising 19 clinically nongoitrous cuthyroid srlhjects; details of the study design and specimen collecting and processing procedures have bern reported elsr,where.1 Briefly, complete collections of diet, and urinary and fecal excretion werP made from one female member of each family (hereafter called balance subjects) for 5 conscc’~~tivc study days CMonday through Friday) during 1 week ( the day-to-day period ) and or)

From

National

Institute

of .irtlwifis

and

Metabolic

Heabh, Public Health Service, U. S. Department Bethesdu, Maryland. Received for publication Nov. 6, 1964. *Since these determinations were made in serum. SII as equivalent to PII, the more commonly Ilsed crntration in plnsma.

Diseases,

of Health,

National

Education,

SII is used in this report. trrln cqxessing inorganic

1nstitutc.s and

of

Welfare,

We regard iodine con-

699 hlETABOLISM,

\‘oL.

I,$.

No. 6 ( ]VNE).

I!?65

700 1 randomly

VOUGHT selected

day in each of 5 weeks

(the

week-to-week

period).

AND

LONDON

The balance

sub-

jects and the other I4 family memhers followed their usual habits and customs with regard to the selection and preparation of food, and were requested to pursue their usual habits of work, recreation and other routine activities during the study period. The only change in diet imposed and table.

by the study was the elimination

of iodized

salt from the kitchen

Blood sera, saliva, and casual urine samples were collected 1 to 2 hours after the cvening meal from all 19 persons on 3 randomly selected days during the day-to-day period and on each study day of the week-to-week period. Data for this report include 139 determinations of SII, 146 determinations of the SSR, 148 ST1 and 81 SPBI determinations from all 19 subjects. In addition to this, 27, 31 and 31 paired observations, respectively, of daily dietary iodine intake vs. SII, STI, and SSR were available from 4 of the 3 balance subjects. Data from the fifth balance subject was excluded because she received a multivitamin tablet her dietary coIIections.

containing

a large quantity

of iodine which

was not added to

The diets were refrigerated in the patients’ homes and picked up daily by a staff member. Diets were processed by homogenization and lyophilization methods reported previously.lJ Blood was collected in iodine-free vacutainers 1% to 2 hours after the evening meal. After a clot had formed, blood was centrifuged, the serum separated and frozen until shipment to the laboratory. Mixed saliva was collected during paraffin stimulation (dental utility wax) for exactly 4 minutes. The volume of each specimen was measrrretl and subsamples were sent to the laboratory. Chemical iodine

analyses (total iodine and protein bound iodine) were performed using by adding the method of Zak as modified by Benotti. :i” Salivary proteins were precipitated 10 ml. of 5 per cent trichloracetic acid to 0.5 ml. of saliva. Urinary and serum creatinine

were determined by the alkaline picrate method.:~ The SII was calculated from the urinary and serum crcatininc the following

and urinary

iodine using

equation

as previously described:’ .‘l.’ Urinary I (1*g./lOO ml. ) x Serum Creatirline Y 13.(1 i SII (,g./lOO ml.) = Urinary creatinine ( mg./lOO ml.) (mg./lOO ml.) The salivary iodine secretion rate was calculated as follows from the vohime of the saliva escreted per minute and the concentration of iodine in that volume: 4 min. vohime of saliva SSR Kg./hr. = -.-.---________ 4

P ST1 (I*K./llll.)

Y l-30.

RESULTS

Previously we reported that the distribution of daily dietary intakes of the balance subjects was lognormal, i.e., Iogarithms of daily dietary intake had a normal (Gaussian) distribution, whereas the actual values, when @ted, had a skewed distribution with the maximum frequency at lower end of the scale of intake 1evels.l Figures lA, B, 2 and 3 show the distributions of serum inorganic iodine, salivary iodine concentration, and the salivary iodine secretion rate, and these distributions also appear to be lognormal, as illustrated by figures 1A and B. In figure lA, the actual distribution of SII values is shown using a conventional arithmetic abscissa. The same data (fig. 1B) Inc. Boston, *Chemical analyses were performed by the Boston Medical Laboratory, Massachusetts. fThe factor 4.0 was used in the original studies;” subsequently it was demonstrated’ that the tubular reabsorption of iodide was 1wttt.r acwn~ntrrl for hy means of the factor 3.6.

DIETARY

IODINE

ON

SERUM

IiYORGANIC

AND

SALlVARY

IODIKE

50v) is 540iiT tnw :30

-

k

-

:: *20 E 1

-

Z

IO-

2.0

1.0

0

SERUM INORGANIC

3.0

7,5

40

IODINE,~g/100ml

50 -

40 -

2 030 F

-

d IOZ

.2 LOGlO Fig.

.6 ,SERUM

I.0 INORGANIC

1.8

I4 IODINE,

pg/L

l.-Frequency

distribution of serum inorganic iodine (pg./100 ml.). abscissa. B, bottom, same data plotted on logarithmic ;rhscissa. The units are mg. /L. to avoid scale difficulties.

A, top, plotted on arithmetic

plotted on a logarithmic abscissa approximate a Gaussian distribution. The data shown on figures 2 (STI) and 3 (SSR) also have frequency distribuions similar to figure 1B when plotted on logarithmic abscissae. The frequency distribution of salivary PBI (not characteristics of the 4 frequency

shown) also proved to be lognormal. Some distributions are presented in table 1.

VOUGHT

AND

LONDON

go-

lil

30

SALIVARY

Fig. 2.-Frequency

IODINE

70

90

loo+

CONCENTRATION,,U~/~~~~~

distribution of salivary iodine concentration (pg./100 ml. ) .

IO

30

SALIVARY Fig. 3.-Frequency

50

50 IODINE

70 SECRETION,pg

90

loot /HOUR

distribution of salivary iodine secretion rate (pg./hr.) .

Table 2 presents ‘paired” observations of dietary iodine intake vs. SII, ST1 and SSR from the 4 balance subjects. In the first column of table 2 dietary intakes of the 4 balance subjects have been distributed in 7 geometric ranges. Column 2 is the geometric mean of the dietary intake in each range. Columns 3, 4 and 5 are the geometric means of the SII, ST1 and SSR, respectively, in each corresponding range of iodine intake. Apparently, both the salivary iodine concentration and the salivary iodine secretion rate follow the SII closely at the lower levels of dietary intake, i.e., below 167 pg./day. IIowever, at higher levels of iodine intake (above 167 pg./day), the salivary

Table l.--Characteristics of thu Frequency Distribtrfions of Serun~ Inorganic Zodine (SZl), Salivary Total Zodine (STZ), Saficary PBZ (SPRZ) and Salivary Iodine Secretion Rate (SSR) Obsewed in 19 Persons I hl~mbers in pawnthesi5 indicate the, n~~rnber of ohsc~w;~tions. )

Fig;re 4 shwvs the regression and 95 lwr wnt confidence belts of the St1 means of tlrc, 111xm dietx1, intake. The 7 sql~ared points are the geometric SII from table 2. These points are linearly distributed despite the fact that both dietary iodine and thck SII are logarithmically distributed. Therefore, ;i cwventional regression has been used to express the cluantitati\,e relationship lwtwccn SII and dietary irxliw throughout the rimge of dietary intakr ohst*rwd in this studv. The wrwtl lines are the 95 per cent confidence limits of single valuc5 of the SII correspondin, 0 to cwh lcwl of iodine intake. Table :3 shows the correlation coefficients ( and their 9.5 per cent conficlc~~~~~~ limits ) lwtwern dietary iodine intake and a numhw of other parameters ot ioclint~ metabolism. Of- particular intrrest is the close correlation between dietary intake and serum inorganic iodide and salivary total iodine ( r = 0.~j5-7 and r = 0.937, respectively i and the relativelv low correlation coefficient lwtwecn tlietary intake and urinary iodine ex&tion ( I‘ = 0.70~1)). a corl-elation tllat is significantly less than any of the others listed.

704

VOUGHT AND LONDON

DIETARY

IODINE

INTAKE,pg/

DAY

Fig. 4.-Regression of serum inorganic iodide upon daily dietary iodine intake. Squared points are geometric means of iodine intake and SII. Curved lines are 9,5 per cent confidence belts of single (predicted) values of SII corresponding to levels

of dietary intake. The regression equation is as follows: (v = (204 P ,176) + (.00205 I .00067)x.

SII;

x =

dietal?

I);

y =

which accounted for 37 per cent of the 81 observations, the remaining 53 per cent falling between 0.5 and 11.1, pg./100 ml. The per cent of the ST1 that was protein bound ranged from O-100 with a median of 9.5 per cent. In only 3 instances did the SPBI/STI exceed 50 per cent. No significant correlation was found between the SPBI and dietary intake, fecal iodine excretion, fecal nitrogen excretion, SIl, serum PBI, urinary iodine concentration or urinary creatinine concentration. DISCUSSION

Oddie et al. noted that the distribution of thyroidal radioiodine uptakes is lognormal.” The lognormal distributions of SII and the linear dependence of SII on dietary iodine intake give rise to solne interesting implications with respect to iodine storage and balance. In 1949, Stanley observed,” and others verified,7px that the accumulation of stable iodide by the thyroid varied directly with the PI1 (or SII). Wagner et al. further hypothesized that within the physiologic ran,ge the rate of accumulation of stable iodide approximates a first order reaction, i.e., the rate of thyroidal accumulation of stable iodide is proportional to the PI1 .n In these subjects the modal SII was 0.25 pg./100 ml. and the distribution of the SII’s was skewed; it follows that most of the time their thyroidal accumulation of iodide was minimal. However, on 14 or 10 per cent of the study days the SII’s exceeded 2.5 pg./100 ml. Therefore, on those days the amount of iodine accumulated should have exceeded the modal or usual accumulation by at least tenfold. What happened to the excess iodine? Hormonal blood levels as measured bv the PBI and BE1 did

DIKTAHY

IODJNE

ON

SERUM

INORGANI(:

Table S.-Correlation Coeficients Dietary Iodine Intake (pg./day)

ASD

No. of Paired Observationr N

SII ( renal ckurancc) Salivary 1 Salivary I. see’. rate Urinary pills fecal rscrction” SII (TI Illillrls PBI)

pg./ 100 ml. pg./ 100 ml.

ITrinary Irrinary

pg./L pg./thg

“Total

I, c’onc. 1 twwtiont daily

collections

t Total 21 lro~w rnkw

/Lg./h.

of urine collections.

70.5

IODINE

(and 95 Per Cent Confidence Limits) between and Other Parameters of lodine Metabolism

Units

pg./‘hy pg./100

SALIVBRY

95’;

Confide,,<.<* Limits

.88X

.X&J-,944 .HFiS-.92X .YO3-,875

“9

.8.50 ,780

.HlH-,759

38 38

.764 ,709

.789-,743 .7:3sJ-.wJ

27 31 31 3”

ml.

Correlation Coefficients I‘

.9.5, ,037

.867-.x:30

ant1 ftzccs.

not change significantly during the study period, and there was no evidmcca of increased hormone production or degradation as indicated by fecal iodints excretion or changes in the basal metabolic rate. ’ Thus, if the excess iotlint~ did not appear as hormone in serum or feces, it could have either remained in the gland or emerged as nonhormonal iodine. The intake and escrtation data of these subjects suggest that the excess iodine did not remain in thus gland but rapidly emerged as nonhormonal iodine, because onlv on the fry’ davs of very high iodine in the diet did iodine intake exceed excretion. OII most studv -days iodine excretion exceeded iodine intake. Explan&on ‘of the consistent excess of iodine excretion over intake is difficult onlv if one postulates that the amount of excretion from the boci\~ must exactlv equal the amount of intake. However. if the amount of iodine accumulation bv the thyroid is proportional to the dietarv intake and the loss of hormonal plus nonhormonal iodine from the gland and the renal clearanccl of iodine arc relatively constant, then the amount of iodine eliminated during a period of time could esceed intake during that period. This leads to thts hypothesis that the rate of iodine excretion from the whole body is proportional to (but not necessarilv equal to) the rate of intake. Data from this and ;I previous balance study’ are consistent with this hypothesis. Kustagi”’ ha< demonstrated than an analogous situation of “usual” negative balance (‘aI I esist for the trace elements, lead. cadmium, and chromium, Tht~ times of collection of blood, saliva, and urine specimens were such tilat the salivarv iodide clearance could not be Clccurately calculated. The ratios of STI: SII (table 2) ranged from 9.6-25.0, values that are in accordance \\TitIl those of Freinkel and Inghar ” based on their radioisotope studies. The STI: SII ratios were relatively constant (9.6-11.3) at intake levels of 167 +r./da~. and below; but at intake levels 393, 631, and 1117 pg./day they increased to 15.9. 25.0, and lS.6, respectively. Our data are limited at the higher levels and these preliminary results need confirmation, since these observations SII~gest that the STI:SII ratio (and probably the salivarv i iodine clearance 1 ma\ increase out of proportion to the SII above some undefined dietarv intakcx 1~~1s so far as we can determine, the presence of I’B112i in human saliva h:ls not bern reported previollsly, but Schein and Tung reported that I’“‘-labelcti

706

VOUGH’r ASI)

albumin

injected

this study

intravenously

confirm

significance

in man

and extend

of salivary

these

appeared

earlier

PBI remains

in saliva.‘”

o&r\-ations,

The

LONllON

data

from

but the nature

and

obscure.

The SII’s of these subjects cover a wider range (0.09-7.0 pg./IO0 ml.) than has been reported heretofore.‘:‘-‘;’ IVayne, Koutras and Alexander, using I “’ to estimate PII, found a range of 0.04-0.57 pg./100 ml. among healthy people

in Scotland.‘”

from fasting PI1

levels,

reflect SII

whereas

nearly

from

pg./100 The

Since

individuals,

our data

maximal

our

data

these

was

0.204

group

equivalent

dietary

patients

were most

low

in iodine

iodine

intake

of the

iodine

gastrointestinal

absorption. bound

protein the

SII

possibility

ai

that

than iodide

most

intake

sera

determined

limits

in this report,

that

the

intake

a high

meals

content.

Furthermore,

supports

the concept in food

serially

the

and the I’“” isotope correlation

the

technic

iodine

demonstrated

used

high

before

that

process

or during

the serum

40 per cent

in this

study,li

iodine

that these

total higher

thus

compounds subjects

was no significant

escretion

Scottish between

that the digestive to iodide

can absorb probable

between

by the

correlation

is on the average

It appears

and fecal

mean

of O-O.64

studied

ingested

we demonstrated

differem?

in their food, since there

in vie>\+ of the

urines)

close agreement.

3 persons

we found

or intestine

is not excluded.

iodine

Finally,

as described

by

and

by more than 0.03 rg./lOO ml.“’ \Ve have

Previously

the stomach

data

minimal

the calculated

\vith confidence of

of their

represent

postprandial

PII’s

compounds

iodine

all of the iodine

between

the

we suspect

iodine,

nearly

ml.

results .a Since

iodine,

and dietary

converts

that

the day did not fluctuate

give

and

than

from

At zero dietary

pg./100

reported

shown that SII determinations, technic

SII

(collected

PI1 levels.

obtained

that their results

ml.: at this level the 2 sets of data are in remarkably

Scottish

throughout

SII

investigators

it is conceivable

the. other

absorbed correlation

(pg./clay ) .’

degree

of correlation

between

why cannot dietary iodine, SII, STI, SSR, urinary and total iodine excretion, one or the other of these measurements be usctl to estimate dietary iodine intake?

The answer

equivalence

is that any one of them can bc used, if there

between

iodine

intake

and iodine

output.

is a one-to-one

In these

subjects,

as a

group, approximate iodine “balance” of the group as a whole was verified bp direct observation of their intake and excretion; but individually not one was in exact

iodine

balance

fore, that another iodine

balance.

estimates

over the periods

group of subjects In this event,

of iodine

none

could

studied.

It is quite

be in either

of the parameters

possible,

“positive” could

there-

or ‘*negative”

provide

reliable

intake. ACKNOWLEDGMENTS

We

are

statistical assistance

grateful

to Dr.

analysis of the with collection

Charles

Roberts and to Miss Marilyn and data, and to Xlr. F. A. Brown and processing of specimens.

Driver for assistance with Mr. James C. Eckloff for

REFERENCES 1. Vought, Iodine

R. L., and London, \V. T.: intake and excretion in healthy subjects. Am. J. non-hospitalized

7. -,

Clin. Nutrition 15: 124, 1964. -, Lutwak, L., and Dublin, T. D.: Reliability of esHmates of serum in-