Caballero B. (ed.) Encyclopaedia of Food Science, Food Technology and Nutrition. Ten-Volume Set

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digested than that of cows’ milk because the fat glob-

ules are smaller in goats’ milk. However, there is no

scientific evidence to confirm this claim. Nearly 20%

of the fatty acids of goats’ milk fat are in the category

of short- and medium-chain length (4–12 carbons).

Cows’ milk fat contains only about 12% of fatty

acids in this category. This difference may contribute

to a greater ease in the digestion of goats’ milk fat as

lipase attacks ester linkages of such fatty acids more

readily than those of longer chains.

0024 One of the most important contributions of milk to

human nutrition is the supply of calcium and phos-

phate. Goats’ milk contains about 120 mg 100 ml

1

300 mg per serving of Ca, and 100 mg 100 ml

1

250 mg per serving of P. These concentrations are

similar to those in cows’ milk. Human milk contains

much lower levels of these minerals, with only about

25% as much calcium and * 15% as much phos-

phorus. Therefore, goats’ milk provides an excess of

calcium and phosphorus in relation to energy for

human infants. Most milks, including goats’ milk as

well as human and cows’ milk, are deficient in iron.

Iron is absorbed and poorly retained from most food

sources. This metal is absorbed better from human

milk than from cows’ milk due to a higher level of

lactoferrin in human milk. It should be noted that both

goats’ and cows’ milks contain higher concentrations

of potassium and chloride than human milk. These

milks should be diluted before feeding to human

infants in order to prevent the onset of acidosis.

Goats’ Milk Products

0025 Traditionally, goats’ milk was produced on small

farms for home consumption more economically

than cows’ milk. However, nowadays, fresh goats’

milk is sold pasteurized in a variety of packaging in

supermarkets and health food stores in the USA.

Yogurt, icecream, cheese, and powdered milk are

also considered to be specialty products in many

western countries.

0026 Pasteurized and homogenized goats’ milk products

are available in US markets, including 2% fat and

whole milk, with or without fortification of vitamins

A and D.

0027 Yogurt and other fermented milks have been made

from goats’ milk for centuries. Yogurt products have

been shown to be effective in the prevention and

treatment of gastrointestinal disorders, such as diar-

rhea and infantile gastroenteritis, due to the anti-

microbial activities of probiotic cultures in the gut.

Yogurt and other fermented milks are also reported

to have other health benefits, including blood

cholesterol reduction and possible cancer prevention.

Goats’ milk yogurt can be made in a similar manner

to cows’ milk yogurt. Because of the low casein con-

tent in goats’ milk, the most realistic and economical

approach for the production of goats’ milk yogurt

with good texture and consistency is through fortifi-

cation of goats’ milk with milk powder and/or stabil-

izers. A probiotic goats’ milk yogurt with improved

texture by enzymatic cross-linking has been de-

veloped in the author’s laboratory at the University

of Vermont. Goats’ milk is also suitable for the pro-

duction of other functional fermented products, such

as kefir and dietary supplements, e.g., Lactobacillus

acidophilus capsules or tablets.

0028Goats’ milk icecream is being produced by a

number of small companies, in both the USA and

other countries. Because goats’ milk products are

considerably more expensive than comparable cows’

milk products, premium icecream is warranted in

order to attract consumers. A premium icecream

should contain a high fat-to-milk solids nonfat

(MSNF) ratio. A typical premium goats’ milk ice-

cream mix usually contains 14% fat, 10% MSNF,

18% sweetener, 1.5% egg yolk solids, and 0.25%

stabilizer-emulsifier.

0029Over 400 varieties of goats’ milk cheese are listed

in the Agricultural Handbook of the US Department

of Agriculture (No. 54–4). The large number of var-

ieties of cheese made from goats’ milk have resulted in

a great diversity in the nature of the products. The

most important cheeses made from goats’ milk include

fresh cheeses (che

vre), ripened cheeses (Cheddar,

Gouda, and Roquefort), and others such as whey

cheese (ricotta). France offers the best goats’ milk

cheeses, many of which are surface-ripened. The chem-

ical composition of some commercial goats’ milk

cheeses manufactured in the USA is shown in Table 7.

0030Other commercial goats’ milk products, such as

powdered milk, butter (also called ghee in India), and

evaporated milk arealso being produced commercially

in the USA and other countries. The manufacturing

tbl0007Table 7 Composition of selected commercial goats’ milk

cheeses in the USA

Nutrients Fresh soft Feta Cheddar Shepherd’s

hard

Moisture (%) 59.8 52.3 41.7 31.6

Fat (%) 22.5 25.3 26.6 33.1

Protein (%) 19.8 25.1 30.3 28.9

Ash (%) 1.74 4.30 3.60 3.93

Calcium (mg 100 g

1

) 172 639 599 1035

Phosphorus (mg 100 g

1

) 275 544 526 737

Potassium (mg 100 g

1

) 25.8 62.2 11.0 54.4

Sodium (mg 100 g

1

) 416 916 361 285

Magnesium (mg 100 g

1

) 14.6 17.6 42.0 61.7

Zinc (mg 100 g

1

) 0.91 1.55 0.65 1.87

2948 GOAT/Milk

technologies of these products are similar to those for

corresponding cows’ milk products.

See also: Carbohydrates: Classification and Properties;

Cheeses: Types of Cheese; Fatty Acids: Properties;

Infants: Nutritional Requirements; Lactose; Protein:

Food Sources; Yogurt: Dietary Importance

Further Reading

Barillet F and Zervas NP (1999) Milking and Milk Produc-

tion of Dairy Sheep and Goats – Proceedings of the Sixth

International Symposium on the Milking of Small

Ruminants. Athens, Greece, September 26–October 1,

1998. Wageningen, The Netherlands: Wageningen Pers.

Guo MR (1993) Goat’s Milk and Its Product Technology

(in Chinese). Harbin, PR China: Heilongjiang Science

and Technology Publishing House.

Guo MR, Wang SP, Li Z and Kindstedt PS (1998) Ethanol

stability of goat’s milk. International Dairy Journal 8:

57–60.

Guo MR, Dixon PH, Park YW, Gilmore JA and Kindstedt

PS (2001) Seasonal changes in the chemical composition

of commingled goat’s milk. Journal of Dairy Science 84:

E79–E83.

Haenlein GFW (1996) Status and prospects of the dairy

goat industry in the United States. Journal of Animal

Science 74: 1173–1181.

Haenlein GFW and Ace DL (1984) Extension Goat Hand-

book. Goat Milk Versus Cow Milk. Fact Sheet E 1–3.

Washington, DC: US Department of Agriculture.

Jenness R (1980) Composition and characteristics of goat

milk: review 1968–1979. Journal of Dairy Science 63:

1605–1630.

Juarez M and Ramos M (1986) Physiochemical Character-

istics of Goat Milk as Distinct from those of Cow Milk

of International Dairy Federation Brussels: no. 202,

54–67.

Loewenstein MM (1982) Dairy goat milk and factors

affecting it. In: Proceedings of the Third International

Conference on Goat production and Disease, pp.

226–236. Scottsdale, AZ: Dairy Goat Journal Publishing

Company.

Park YW (1990) Nutrient profiles of commercial goat milk

cheeses manufacture in the United States. Journal of

Dairy Science 73: 3059–3067.

GOITROGENS AND ANTITHYROID

COMPOUNDS

J Vanderpas, Faculte

decine, FUNDP, Namur,

Belgium

Biochemistry of Thyroid Function and

Environmental Factors

0001 Besides iodine deficiency, certain environmental

agents, both naturally occurring and synthetic, inter-

fere with thyroid function. They may cause goiter and

thyroid dysfunction by acting directly on the thyroid

gland or indirectly by altering its regulatory mech-

anisms and thyroid hormone homeostasis. They are

thus called goitrogens or antithyroid compounds,

according to their main effect on thyroid volume or

on thyroid hormone metabolism.

000 2 Figure 1 shows some of the principal steps in

thyroid hormone synthesis, secretion, and metab-

olism which can be influenced by environmental goi-

trogens. The unique known function of iodine in

mammals is its role in the synthesis of thyroid hor-

mones. The uptake of iodide by the thyroid gland is

stimulated by the pituitary hormone thyroid-stimulat-

ing hormone or thyrotropin (TSH), and its serum

concentration can be multiplied > 100 times in some

extreme environmental conditions of iodine defi-

ciency and goitrogen toxicity. Some goitrogens, such

as thiocyanate and isothiocyanate, interfere with

iodide uptake.

0003After being concentrated by the thyroid gland,

iodide is oxidized and bound to some specific tyrosyl

residues of thyroglobulin, forming monoiodotyrosine

(MIT) and diiodotyrosine (DIT); oxidation of iodide

and iodination of selected tyrosyl residues is catalyzed

by a heme-containing membrane-bound enzyme,

thyroperoxidase (TPO). The same enzyme couples

two iodotyrosines to form thyroxine (T

; four iodine

atoms) and triiodothyronine (T

; three iodine atoms).

The ratio of T

to T

in thyroglobulin is closely

dependent on serum TSH concentration and iodine

supply: in euthyroidism (normal healthy function of

the thyroid gland), 85% of the hormonal content

of the thyroid is represented by T

, while in the hypo-

thyroid state, the ratio of T

within the thyroid

is closer to unity. Most of the goitrogens (phenol

derivatives, dihydrobenzoic acid, flavonoids, goitrin,

disulfides, polycyclic aromatic hydrocarbons, excess

iodine) interfere with TPO activity.

0004Intrathyroid proteolysis of thyroglobulin results in

the release of T

and T

in the systemic circulation; this

step is inhibited by lithium and excess iodine. Secreted

GOITROGENS AND ANTITHYROID COMPOUNDS 2949

in the systemic circulation, serum T

and T

are bound

to albumin, thyroxine-binding globulin and transthyr-

etin (also named thyroxine-binding prealbumin). The

binding of thyroid hormones to serum proteins is

partly inhibited by flavonoids, resulting in alterations

of circulating free hormone concentrations and adap-

tation of feedback regulation. At the cellular level, the

prohormone T

is deiodinated to the active hormone

by the action of deiodinases; all three isoforms of

deiodinases are selenium-containing enzymes. The

type 1 deiodinase is abundant in peripheral tissues

like liver, kidney, heart, muscle, thyroid; the type 2

deiodinase is the predominant form in the central

nervous system. (See Hormones: Thyroid Hormones;

Iodine: Physiology; Iodine-deficiency Disorders.)

Iodine Excess

0005 Since the first descriptions of efficiency of iodine

supplementation on goiter in 1820, adverse effects

of iodine have been observed.

0006Currently, a number of drugs have a large iodine

content with a very slow metabolism. For example,

amiodarone is a very common antiarrhythmic drug,

and the usual 200-mg tablet contains 75 mg iodine

in an organic form, of which 6 mg is released every

day as free iodine; as the molecule is highly liposolu-

ble, excess iodine persists for months after therapy

cessation. Other compounds rich in iodine are some

X-ray contrast agents, expectorants made from po-

tassium iodide (Quadrinal), and skin disinfectants

such as povidone-iodine (Isobetadine). Maternal

contamination with povidone-iodine has been docu-

mented as a cause of neonatal hypothyroidism.

0007Some goiter endemias result from iodine in excess

in the environment, e.g., ingestion of iodine-rich

seaweed in Hokkaido, Japan, or ingestion of water

contaminated with iodine in Shanxi province, China

(Table 1). An excess intake of iodine, defined as 2 mg

or more daily, inhibits the proteolysis and release of

thyroid hormones and eventually produces hypothy-

roidism.

TSH

TG-T

−

TG-T

TG-DIT

TG-MIT

Circulating T

Se-Diase I

Se-Diase I or II

Nuclear T

receptor

Liver

Cellular level

Thyroid

Pituitary

−

fig0001 Figure 1 Some metabolic steps in iodine metabolism. Pituitary thyrotropin (TSH) stimulates thyroid iodide (I



) uptake, and

enzymatic organification of iodine (I



) by thyroperoxidase (TPO) in mono- and diiodotyrosine (MIT and DIT) which are further coupled

by the same enzyme TPO in tri- and tetraiodothyronine (T

and T

). Part of T

is further deiodinated to T

in the liver by a selenium-

containing enzyme selenium-dependent deiodinase I (Se-Diase I). At the cellular level, the active hormone is T

, which binds to a

specific nuclear T

receptor. T

comes directly from circulating serum T

or from intracellular conversion of T

to T

TG, thyroglobulin.

2950 GOITROGENS AND ANTITHYROID COMPOUNDS

0008 Iodine excess in nonendemic areas involves in the

short term a blockade of iodine organification in

the thyroid gland (Wolff–Chaikoff effect); in most

instances, there is an escape phenomenon after a few

weeks, the thyroid hormonal parameters returning to

normal. In a few subjects, a persistent dysthyroid

function (hypothyroidism or hyperthryroidism) de-

velops by a yet incompletely explained mechanism.

The prevalence of chronic autoimmune thyroiditis

in industrialized countries is correlated with iodine

intake, with the highest prevalence in countries with

the highest intake of iodine, such as the USA and

Japan. Iodine supplementation in areas where iodine

is deficient increases the prevalence of lymphocytic

infiltration of the thyroid threefold, and the preva-

lence of positive serum tests for thyroid antibodies

in such areas rises to over 40% within 0.5–5 years.

Amiodarone-induced hypothyroidism usually occurs

within 18 months, and is seven times more likely to

develop in patients with thyroid antibodies than in

those without thyroid antibodies.

Iodine-Induced Hyperthyroidism

0009 Universal salt iodization was the World Health

Organization plan for iodine-deficient-countries in

Africa, Asia and South America which were previ-

ously known as endemic in 1990–91. The marked

decrease in the prevalence of goiter during the

following years was a striking confirmation of the

effectiveness of universal salt iodization in Africa.

Nevertheless, iodine-induced hyperthyroidism was

clearly documented in two countries. A balance has

to be reached between the desirable daily iodine

supply necessary to prevent goiter (> 100 mg day

1

)

and excessive iodine (> 400 mgday

1

). The risk of

developing iodine-induced hyperthyroidism is small

(< 1% in the general population); it has been impos-

sible to obtain a precise incidence rate up to now; this

incidence rate is increased in the subgroup of women

over 40 years of age with long-standing, nodular, and

potentially autonomous goiter. From experimental

data, it is considered that autonomy of the gland

results from a mutation of TSH-receptor in thyroid

tissue, which renders the hormonal function inde-

pendent of its control by TSH. As long as iodine

deficiency is present, the multinodular goiter is func-

tionally inefficient. With iodine supplement, the

autonomous parts of the gland become active, and

the patient develops hyperthyroidism (sometimes

named Jod-Basedow hyperthyroidism). Even if the

number of cases is low and the clinical signs are

asymptomatic or moderate most of the time (profuse

sweating, weight loss, increased appetite, ocular

changes (upper-eyelid retraction), tachycardia,

change of mood (hyperactivity, fatigability, anxiety) ),

some deaths occurred in relation to the introduction

of universal salt iodization in Africa. It is likely that

the problem is transient in public health terms, as the

primum movens cause – presence in the population of

autonomous thyroid gland due to iodine deficiency –

will decrease with time.

Sulfur-Containing Compounds

0010Antithyroid sulfur-containing organics identified in

vegetable foodstuffs can be divided into two categor-

ies according to the way they act on iodine meta-

bolism: (1) thiocyanate and isothiocyanate-derived

compounds primarily inhibit the active concentration

mechanism of iodide, and their goitrogenic activity

can be overcome by iodine administration; (2) goitrin

(or 1,5-vinyl-2-thiooxazolidone) is analogous to thio-

urea in its action, interfering with the TPO organifi-

cation process, and its action cannot usually be

antagonized by iodine. (See Plant Antinutritional

Factors: Detoxification.)

tbl0001 Table 1 Goiter endemias attributed to goitrogens in foodstuffs or to inadequate supply of trace elements

Cause Country Source Active compound

Goitrogens in foodstuffs Central Africa Cassava Cyanogenic glucoside

Nigeria Cassava Cyanogenic glucoside

Darfur, Sudan Millet Flavonoids

Cyanogenic glucoside

Maranhao, Brazil Babassu ?

Mandioca Cyanogenic glucoside

Tasmania Grass and weeds Isothiocyanate (cheilorine)

Finland Grass and weeds Goitrin

Cauca valley, Colombia Water Coal-derived water pollutants

Eastern Kentucky, USA Water Coal-derived water pollutants

Inadequate supply of trace elements Hokkaido, Japan Seaweeds Iodine overload

Zaire Soil Selenium deficiency

Himalayas Water Fluoride excess

GOITROGENS AND ANTITHYROID COMPOUNDS 2951

Thiocyanate and Isothiocyanate

0011 Thiocyanate and cyanide do not occur in the intact

plant as free anions. They result from the hydrolysis of

a thioglucoside by specific enzymes such as the couple

linamarine–linamarase in cassava when the roots are

crushed. In most populations, crushed roots are de-

toxified by sinking a few days in river water, or by

exposing to sun. In some Central Africa rural ethnic

groups (such as Mbanza and Ngbaka from Northern

Democratic Republic of Congo and Central Africa

Republic), cassava is poorly detoxified, resulting in

an elevated content of cyanide. This last anion is rap-

idly detoxified by sulfur-transferases (also named

rodanese) in the liver and kidney (Figure 2).

0012 The principal vegetables containing thioglucosides

are kale, cabbage, sprouts, broccoli, kohlrabi,

turnips, swedes, rapeseed, and mustard. The main

vegetables containing cyanogenic glucosides are cas-

sava, lima beans, linseed, bamboo shoots, and sweet

potatoes. One of the most widespread mustard oils is

allylisothiocyanate (CH2

—

CH—CH2—N

—

S),

which is the principal mustard oil in cabbage.

0013 The inhibitory action of thiocyanate on iodine

uptake is due to a competitive effect of pseudohalide

with the mechanism of iodide concentration. However,

under experimental conditions, rather high plasma

concentrations of thiocyanate are required for inhibit-

ing iodine uptake by the thyroid gland. In the historical

use of thiocyanate as a vasodilator in hypertension,

administration of 3 g of thiocyanate results in serum

levels in the range of 8.0–15.0 mg dl

1

, far exceeding

the levels attained in populations exposed to environ-

mental thiocyanate overload (around 2.0 mg dl

1

). In

ethnic groups with the highest prevalence of goiter,

cassava is not soaked; the roots are peeled, dried in

the sun for 1 or 2 days, then bruised in a mortar with

corn that has been steeped for 12–24 h in water. The

flour is eaten as a gruel (fuku) prepared in boiling

water. In other ethnic groups of Central Africa where

goiter prevalence is lower, the roots of cassava are

soaked for 2–6 days and then mashed into a pure

which is simmered to form a paste of firm and elastic

consistency. The paste is enveloped in a palm or banana

leaf (chikwangue). The cassava leaves are ground and

extensively boiled before consumption (mpondu).

Table 2 shows the cyanide content of foods before

preparation or ready to eat. Table 3 shows that thio-

cyanate overload in northern Democratic Republic of

Congo is present at birth, resulting from the placental

transfer of maternal serum thiocyanate. Thiocyanate is

not present in excess in maternal milk as compared to a

group of mothers not consuming cassava. Lack of thio-

cyanate overload associated with a stable iodine defi-

ciency (mammary gland does not concentrate iodine in

humans) could explain the relative mitigation of

endemic hypothyroidism in infants of Ubangi during

the breast-feeding period, and the deterioration of thy-

roid function after weaning which is chronologically

associated with the introduction of cassava meals

in food. Figure 3 shows the relationship of iodine

Linamarase

Rhodanese

Liver, kidneyCyanide

−

+ S

2−

Thiocyanate

SCN

−

+ SO

2−

Hydrocyanic acid

+ glucose + HCN

Linamarine

O-glucose

fig0002 Figure 2 Enzymatic degradation of cassava linamarin by

autolysis due to linamarase, and pathway of endogenous con-

version of cyanide into thiocyanate with liver and kidney sulfur

transferase (rhodanese). Reproduced from Goitrogens and

Antithyroid Compounds, Encyclopaedia of Food Science, Food

Technology and Nutrition, Macrae R, Robinson RK and Sadler MJ

(eds), 1993, Academic Press.

tbl0002Table 2 Comparison of cyanide content of foods before

preparation or ready to eat, in Ubangi, Zaire

Food Cyanide

(mgkg

1

)

(mean +

SEM)

Before preparation

Cassava leaves 92.1 + 21.6

Cassava and corn 19.8 + 2.5

Cassava flour 4.5 + 2.7

Wild yams 7.3 + 0.4

Cultivated yams 8.5 + 0.3

Bananas (bananes plantain) 4.4 + 0.7

Ready to eat

Sun-dried cassava root and corn (fuku) 14.2 + 0.7

Soaked and boiled cassava root (chikwangue) 3.5 + 0.4

Boiled assava leaves (mpondu) 8.5 + 0.7

Cane sugar 2.6 + 0.1

Reproduced from Ermans AM, Mbulamoko NM, Delange F and Ahluwalia

R (1980) Role of Cassava in the Etiology of Endemic Goitre and Cretinism.

Ottawa: International Development Research Centre, with permission.

tbl0003Table 3 Thiocyanate concentration in maternal serum and in

cord serum at delivery, and in maternal milk during breast-

feeding in subjects of Ubangi, Zaire

Ubangi, Zaire Belgium t-Test

Maternal serum

at delivery

0.77 + 0.53 0.21 + 0.17 P<0.001

Cord serum 0.78 + 0.56 0.19 + 0.22 P<0.001

Maternal milk 0.33 + 0.15 0.26 + 0.13 NS

NS, not significant.

Reproduced from Vanderpas J et al. (1984) Endemic infantile

hypothyroidism in a severe endemic goitre area of Central Africa. Clinical

Endocrinology 20: 327–340, with permission.

2952 GOITROGENS AND ANTITHYROID COMPOUNDS

deficiency and of thiocyanate overload in neonates and

in children of Ubangi, Democratic Republic of Congo,

with mean serum T

concentration. At birth and during

childhood, thiocyanate overload and iodine deficiency

act in synergy to produce low serum T

concentrations.

Once iodine deficiency has been corrected, the goitro-

genic effect of thiocyanate is no longer present. (See

Cassava: The Nature of the Tuber.)

Smoking

0014 Tobacco smoking is another cause of thiocyanate

overload. In a country with borderline iodine defi-

ciency (Belgium), the risk of neonatal hypothyroidism

seems to be higher in neonates from smoking

mothers. Impaired action of thyroid hormone associ-

ated with smoking in women with hypothyroidism

has also been shown: smoking was associated with

greater serum TSH, total and low-density lipopro-

tein-cholesterol and creatine kinase concentrations,

and prolonged ankle-reflex time. These effects

suggest an interaction of smoking with thyroid

hormone receptors, different from the effects of

thiocyanate. (See Smoking, Diet, and Health.)

Goitrin and Aliphatic Disulfides

0015 On enzyme hydrolysis, a particular thioglucoside

gives rise to progoitrin, which is rapidly converted

to form goitrin. Progoitrin is present in swedes and

turnips. Administration of goitrin to rats for 20 days

induces an enlargement of the thyroid, decreases

iodine uptake by the gland, and decreases T

synthe-

sis. Other sources of goitrin-like compounds have

been detected in various species of herbs and shrubs

of the Barbarea and Residea families.

0016The role of goitrin has been advocated in the devel-

opment of endemic goiter in schoolchildren of Tas-

mania; this goiter could not be prevented by iodine

supplementation. The endemia was attributed to a

goitrogenic factor ingested by cattle from thousand-

headed kale and transmitted by milk. However, only

0.05% of goitrin appears in the milk, and is rapidly

denatured unless the milk is heated immediately.

Goitrin has also been involved as an environmental

goitrogen in Finland.

0017The major components of the volatile compounds

from onion and garlic are small aliphatic disulfides

which depress uptake of radioactive iodide by the

thyroid of rats on a low-iodine diet. Disulfides are

also present in high concentrations (0.3–0.5 g l

1

)in

aqueous effluents from coal-conversion processes; it

is possible that these water contaminants intervene

in the etiology of endemic goiter in the Cauca districts

of Colombia.

Flavonoids

0018Flavonoids are a broadly distributed class of plant

pigments, universally present in vascular plants.

6.1

3.7−15

(39)

1.6−3.6

(41)

0.2−1.5

(40)

1.50 0.93 0.08

7.56.25.6

=120

=132

0−1.3

2.6−15.0

1.4−2.5

5.4

2.8

9.8

5.0 8.7

7.84.82.1

1.50

−4.30 −1.49 −0.61

0.080.61

Maternal urine SCN (mgdl

−1

) Child urine SCN (mgdl

−1

)

(b)(a)

Maternal urine iodine (µg dl

−1

)

Child urine iodine (µg dl

−1

)

6.9

6.5

−4.98 −1.49 −0.92

(40)

11.0

9.1

11.5

10.3

fig0003 Figure 3 Level of serum thyroxine (T

) in (a) newborn babies and (b) children aged 0–7 years according to the urine concentrations

of iodine and thiocyanate (SCN). Reproduced from Goitrogens and Antithyroid Compounds, Encyclopaedia of Food Science, FoodTech-

nology and Nutrition, Macrae R, Robinson RK and Sadler MJ (eds), 1993, Academic Press.

GOITROGENS AND ANTITHYROID COMPOUNDS 2953

They are not synthesized in animal tissues. Their

number exceeds 3000 and new structures are

reported at a rapid rate. All classes of flavonoids

derive their carbon skeleton from cinnamic acid; chal-

cone is the first common intermediate. More than 1 g

of various flavonoids is ingested daily in the western

diet. (See Colorants (Colourants): Properties and

Determination of Natural Pigments.)

0019 Since most flavonoids in foodstuffs are b-

glucosides, they are not hydrolyzed by intestinal

digestive enzymes and pass largely unaltered into the

lower bowel. Microflora in the large intestine hydro-

lyze the flavonoid glucosides to their corresponding

aglycone, and cleave the heterocyclic pyrane ring.

Pharmacokinetic investigations in humans showed

that 3% of an ingested dose of flavonoids (catechin)

is absorbed, with peak plasma levels of 17 mg ml

1

after 1 h and biexponential disappearance from

plasma with mean half-lives of 8.8 min and 2.4 h.

0020 The effect of flavonoids on thyroid hormone

metabolism was discovered in studies of several

substances of plant origin, chemically different from

ascorbic acid, which have been reported to be bene-

ficial in the control of hemorrhage, and have been

referred to as ‘vitamin P.’ The ability of flavonoids to

induce goiter was suggested from many studies in-

volving various plants, e.g., peanuts (arachidoside)

and millet (vitexin, glucosylorientine). Millet flavo-

noids are potent inhibitors of iodine organification,

and flavonoids and thiocyanate interact synergistic-

ally on organifying enzyme TPO. By their structural

homology with thyroid hormones, the flavonoids

interact with thyroid hormone transport, by dis-

placing the hormone from their natural transporters

in human serum (thyroxine-binding prealbumin and

thyroxine-binding globulin).

0021 In human populations, pearl millet (Pennisetum

americanum) is the staple food for millions of people

and livestock in Africa and Asia. Because of its peren-

nial growth, it constitutes the main source of food

energy for the very poor in the semiarid tropics. Pen-

nisetum millet is very rich in polyphenols of the fla-

vonoid type which inhibit TPO. Table 4 compares the

dietary composition and goiter prevalence among

schoolchildren in the Darfur province of western

Sudan. The goiter prevalence is closely linked to the

level of consumption of millet.

Selenium Deficiency-Related Thyroid

Dyshormonogenesis

0022Selenium is incorporated as selenocysteine in all three

forms of deiodinases by a specific transfer ribonucleic

acid (tRNA) at the cotranslational level, with a same

anticodon as the tRNA binding to the amber stop

codon, TGA. SECYS-tRNA in place of STOP-tRNA

is incorporated in case of a stem-and-loop mRNA

structure (SECYS-mRNA element) present on the

transcribed mRNA. At least for deiodinase 1, the

activity is reduced to 10% of the initial level when

selenium is not incorporated. The presence, but not

its catalytic function, is also demonstrated by molecu-

lar biology in deiodinases 2 and 3.

0023In iodine- (Figure 4) and selenium-deficient sub-

jects of northern Democratic Republic of Congo, sel-

enium supplementation in the absence of iodine

supplementation involves a decrease of serum T

and of serum reverse T

concentrations; in subjects

with no loss of thyroid functional capacity (iodine-

deficient, otherwise normal schoolchildren), the

decrease of serum T

was not accompanied by an

aggravation of hypothyroidism, as serum T

and

serum TSH remained stable. In contrast, in subjects

with a low thyroid functional capacity (myxedema-

tous cretins), the decrease of serum T

was accompan-

ied by an increase of serum TSH and a decrease of

serum T

, clearly showing that an aggravation of

hypothyroidism occurred after selenium supplemen-

tation in the absence of sufficient iodine supply (Figure

5). According to these results, in areas which are

both iodine- and selenium-deficient, it is mandatory

to correct iodine deficiency before selenium supple-

mentation; selenium deficiency should be corrected

thereafter too.

0024InTibetanvillageswithanelevatedprevalenceof

endemic osteochondrodysplasia, named Kashin–Beck

disease, and related to selenium deficiency, iodine

deficiency and selenium deficiency are still more

severe than in northern Democratic Republic of

Congo. Nevertheless, endemic myxedematous cretin-

ism is much less frequent in Tibet than in iodine-defi-

cient areas of Central Africa. The current hypothesis is

that at least three factors interact to involve endemic

myxedematous cretinism: iodine deficiency þ selen-

ium deficiency þ thiocyanate overload.

0025Recent experimental work has shown that selen-

ium deficiency in rats subjected to antithyroid com-

pounds involves thyroid fibrosis: this could be the

tbl0004 Table 4 Dietary composition and goiter prevalence among

schoolchildren in Darfur province, western Sudan

Locality Goiter prevalence (%) Energyintake (%)

Millet Sorghum Wheat Fat

Kas 61 74 10 6 10

Tawaila 45 67 12 7 14

Nyala 12 37 27 20 16

Reproduced from Osman AK and Fateh (1981). Factors other than iodine

deficiency contributing to the endemicity of goitre in Darfur province

(Sudan). Journal of Human Nutrition 35: 302–310, with permission.

2954 GOITROGENS AND ANTITHYROID COMPOUNDS

Before

+Se

(a)

100

120

140

160

180

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

18.0

20.0

After Before

Normal range

Serum T

(nmol I

−1

)

Serum T

(nmol I

−1

)

After

(b)

fig0005 Figure 5 Effect of 2 months of oral selenium (Se) supplementation (50 mg Se daily as selenomethionine) in Se- and iodine-deficient

subjects of Zaire on serum thyroxine (T

) concentration. (a) Normal schoolchildren; (b) myxedematous cretins. Note the different

scales of serum T

. Reproduced from Goitrogens and Antithyroid Compounds, Encyclopaedia of Food Science, Food Technology and Nu-

trition, Macrae R, Robinson RK and Sadler MJ (eds), 1993, Academic Press.

Thyroid gland

TSH

Euthyroid state

Hormone secretion by

normal follicles

Hormone secretion by autonomous follicles

Hyperthyroidism

II III IV V

fig0004 Figure 4 Proposed scheme of iodine-induced hyperthyroidism (also named Jod-Basedow hyperthyroidism). In an iodine-deficient

environment, chronic thyroid-stimulating hormone (TSH) stimulation involves a multinodular goiter. This also promotes the develop-

ment of some autonomous follicles. As long as the iodine substrate is not available, the hyperfunctioning gland remains silent, i.e.,

without concurrent clinical hyperthyroidism. Once iodine is introduced, for example, with universal iodized salt, some predisposed

people (peculiarly women > 40 years) are at risk of developing hyperthyroidism. Reproduced from Braverman LE and Utiger R (eds)

(1996) Werner’s and Ingbar’s The Thyroid, 7th edn. Philadelphia: JB Lippincott, with permission.

GOITROGENS AND ANTITHYROID COMPOUNDS 2955

clue for the physiological mechanism of thyroid

involution in endemic myxedematous cretinism.

Lithium- and Fluoride-Induced Thyroid

Dysfunction

0026 Lithium carbonate is used for manic-depressive dis-

orders. Goiter occurs in 5–10% of treated patients,

and biological hypothyroidism is reported in 5% of

treated patients.

0027 The best recognized effect of lithium on the thyroid

is the inhibition of hormone release. The mechanism

of action is still controversial and may involve the

calcium/1,4,5-phosphatidylinositol pathway.

0028 Lithium excess has been advocated as a cofactor of

endemic goiter in Venezuela, where dietary iodine

and protein intakes are low.

0029 The consumption of ground water containing

higher levels of fluoride has been reported to influ-

ence the prevalence of goiter. In 13 villages in the

Himalayas, for almost the same iodine intake, the

prevalence of goiter varied with different levels of

fluoride and hardness of drinking water.

Phenol Derivatives

0030 Humic substances are heterogeneous, high-molecu-

lar-weight, complex polymeric, yellow-black com-

pounds which constitute the major organic fraction

of soil and water. They are involved in the coalifica-

tion process and are considered to be both precursors

and decomposition products of coals. They include

resorcinol, catechol, orcinol, phloroglucinol, pyro-

gallol, 2,6-dihydroxytoluene, 3,5-dihydroxybenzoic

acids, and phtallic acids. These compounds are re-

leased into the water or soil, where decomposition

occurs.

0031 Resorcinol and hexylresorcinol are present in many

topical antiseptic preparations; resorcinol has been

used as an antifungal, antimicrobial, and keratolytic

agent in concentrations of 2–20% in lotions, creams,

and ointments. Hydroquinone and catechol are

widely used in the photography industry as develop-

ers of black and white pictures or X-ray films, and in

the rubber industry as antioxidants or as stabilizers of

radical polymerization. Dihydroxyphenols are major

components of cigarette smoke. They originate from

decomposition of flavonoids.

0032 A variety of phenolic compounds, articularly di-

hydroxyphenols, and related compounds with meta-

substitution in a benzene ring, inhibit TPO-mediated

iodide organification, in vivo as well as in vitro.(See

Phenolic Compounds.)

0033 Investigations into the causative factors in endemic

goiter in iodide-sufficient areas of the Cauca valley,

Colombia, and in the coal-rich Appalachian area of

eastern Kentucky, USA, have demonstrated a signifi-

cant correlation between watersheds rich in organic

matter (coal and shale) and the high incidence of

goiter.

Polycyclic Aromatic Hydrocarbons (PAHs),

Including Dioxins

0034Polychlorinated biphenyls (PCBs) and polybromi-

nated biphenyls (PBBs) are commonly incorporated

into electrical apparatus, flame-proofing materials,

hydraulic fluid, varnishes, and other types of protect-

ive coatings. These compounds are almost insoluble

in water. (See Polycyclic Aromatic Hydrocarbons.)

0035Acute toxicity syndromes of PCB exposire in rela-

tively large quantities have been described after an

accidental industrial contamination in Japan in which

over 1000 people were poisoned (Yusho disease).

Alterations in thyroid function during this epidemic

are not documented. In another study, 36 of 86

men who were employed in a PBB-manufacturing

plant were reviewed for thyroid abnormalities; the

prevalence of antimicrosomal antibodies (4 of 35)

was statistically significantly higher than the 2.8%

expected in a reference population. These data on

the possible effect of goitrogens in thyroid auto-

immunity are similar to those reported in rats submit-

ted to other PAHs; goitrous lymphocytic thyroiditis

has been observed after administration of the carcino-

gens, methylcholanthrene and dimethylbenzanthra-

cene, in Buffalo inbred strains of rats, while other

strains (Fisher rats) were not susceptible.

See also: Cassava: The Nature of the Tuber; Colorants

(Colourants): Properties and Determination of Natural

Pigments; Hormones: Thyroid Hormones; Iodine:

Physiology; Iodine-deficiency Disorders; Phenolic

Compounds; Plant Antinutritional Factors:

Detoxification; Polycyclic Aromatic Hydrocarbons;

Smoking, Diet, and Health