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

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0034 The factors that contribute to age-related bone loss

are incompletely understood. Potential contributory

factors include:

0035 Hormonal factors – estrogen deficiency is an im-

portant determinant of menopausal bone loss. Both

osteoclasts and osteoblasts possess estrogen recep-

tors and thus may be influenced by estrogens.

Declining production of sex hormones may also

contribute to age-related bone loss in men, al-

though this is less well documented than in women.

Changes in the growth hormone–insulin-like

growth factor I axis may contribute to age-related

bone loss. The age-associated increase in parathy-

roid hormone is also thought to be a contributory

factor.

0036 Nutritional factors have also been implicated;

calcium deficiency due to an inadequate intake,

reduced intestinal absorption, or increased renal

deficiency may contribute to age-related bone

loss. Vitamin D deficiency is common in many

elderly populations and results in secondary hyper-

parathyroidism and increased bone turnover. Mal-

nutrition, also common in some older individuals,

may lead to acceleration of bone resorption, pos-

sibly as a result of reduced protein intake. Vitamin

K-deficiency may contribute to an increased risk of

osteoporotic fractures, although the pathogenesis

of this condition has not been precisely delineated.

0037 Heritable factors – age-related bone loss can be

very dramatic in certain individuals, and this de-

cline cannot be attributed solely to hormonal or

nutritional factors. This has led some researchers

to hypothesize that genetic programming, when

triggered, may lead to bone loss. However, the

identity of genes involved in this process remains

elusive.

0038 Environmental factors – decreasing physical

activity with age is another likely contributor to

age-related osteopenia, in both men and women.

Similarly, smoking, alcohol, and some medications

(such as glucocorticoids and anticonvulsants) may

contribute to an excessive rate of bone loss in some

elderly individuals.

Age-Related Fracture and Osteoporosis

0039 Advancing age is a relatively strong risk factor for an

osteoporotic fracture. Osteoporosis is defined as a

systemic skeletal disease characterized by low bone

mass and microarchitectural deterioration of bone

tissue, with a consequent increase in bone fragility

and susceptibility to fracture. Fragility fractures are

the hallmark of osteoporosis and are particularly

common in the spine, hip, and distal forearm (Colles

fracture), although they can occur throughout the

skeleton. These fractures constitute a major public

health problem. Osteoporosis can be classified into

type I (or postmenopausal osteoporosis) and type II

(or senile osteoporosis). A more indepth discussion on

the etiology, treatment, and prevention of osteopor-

osis as well as its consequences for quality of life are

discussed elsewhere in this encyclopedia. (See Osteo-

porosis.)

0040Other bone disease states result from nutritional

deficiency, e.g., rickets/osteomalacia (See Cholecalci-

ferol: Properties and Determination; Physiology), or

from genetic defects, e.g., osteopetrosis (character-

ized by defective osteoclast function and a consequent

failure of bone remodeling) or osteogenesis imper-

fecta (characterized by an osteopenia associated

with recurrent fracture and skeletal deformity stem-

ming from a qualitative or quantitative abnormality

of type I collagen).

See also: Body Composition; Calcium: Physiology;

Cholecalciferol: Properties and Determination;

Physiology; Osteoporosis

Further Reading

Baron R (1999) Anatomy and ultrastructure of bone. In:

Murray FJ (ed.) Primer on the Metabolic Bone Diseases

of Mineral Metabolism, 4th edn, pp. 3–10. Philadelphia,

USA: Lippincott Williams & Wilkins.

Canalis E (1996) Regulation of bone remodeling. In:

Murray FJ (ed.) Primer on the Metabolic Bone Diseases

of Mineral Metabolism, 3rd edn, pp. 29–34. Philadel-

phia, USA: Lippincott-Raven.

European Commission (1998) Report on Osteoporosis in

the European Community – Action for Prevention.

Luxembourg: Office for Official Publications of the

European Communities.

Lian JB, Stein GS, Canalis E, Robey PG and Boskey AL

(1999) Bone formation: osteoblast lineage cells, growth

factors, matrix proteins, and the mineralization process.

In: Murray FJ (ed.) Primer on the Metabolic Bone Dis-

eases of Mineral Metabolism, 4th edn, pp. 14–30. Phila-

delphia, USA: Lippincott Williams & Wilkins.

Mundy GR (1999) Bone remodeling. In: Murray FJ (ed.)

Primer on the Metabolic Bone Diseases of Mineral

Metabolism, 4th edn, pp. 30–38. Philadelphia, USA:

Lippincott Williams & Wilkins.

Rodan GA (1998) Control of bone formation and resorp-

tion: biological and clinical perspective. Journal of

Cellular Biochemistry 30/31: 55–61.

Thomson BM (1998) Bone: composition, metabolism and

bone growth. In: Sadler MJ, Strain JJ, and Caballero B

(eds) Encyclopedia of Human Nutrition, vol. 1, pp.

185–190. San Diego: Academic Press.

Vaughan J (1981) Bone as a tissue. In: Vaughan J (ed.) The

Physiology of Bone, 3rd edn, pp. 1–26. Oxford: Claren-

don Press.

BONE 565

BORON

C D Hunt, Grand Forks Human Nutrition Research

Center, Grand Forks, ND, USA

Background

0001 Boron is a light, nonmetallic element known to be

essential for all vascular plants and some lower plants

and prokaryotes. The discovery of two classes of

naturally occurring organoboron compounds has

provided some insight into the biomolecular role of

boron. Recent research findings indicate that boron

is important for the embryological development of

lower vertebrates. In human and subhuman animals,

boron modifies, and possibly regulates, energy sub-

strate and mineral metabolism, and immune function.

Boron Chemistry

Boron Structure and Bonding

0002 Boron is the fifth element in the periodic table and the

only nonmetal in Group III. Although boron has five

electrons and a ground-state electronic configuration

of 1s

, it is always trivalent; simple electron

loss to form a cation does not occur in boron chemis-

try. Boron has a small atomic size; the first ionization

potential of boron (800.5 kJ mol

1

) is rather high,

and the next two are much higher (2426.5 and

3658.7 kJ mol

1

). It requires less energy to promote

one 2s electron and mix the remaining 2s electron

with the resultant 2p

and 2p

electrons to form a

hybridized valence state of the sp

type. The three

resulting B–X s-bonding electrons can be regarded

as occupying three equivalent sp

hybrid orbitals.

Thus, the characteristics of the boron atom dictate

covalent rather than ionic bonding. BX

compounds

have a trigonal–near planar configuration.

0003 In geological systems, boron neither occurs free nor

binds directly to any element other than oxygen

except for trivial exceptions, e.g., NaBF

(ferrucite)

and (K,Cs)BF

(avogadrite). Only organoboron com-

pounds are apparently important in biological systems

during normal physiological conditions, and they

are defined for this discussion as those organic com-

pounds that contain B–O bonds, i.e., the orthoborates

(B(OR)

, (RO)B(OR

)

and (RO)B(OR

)(OR

), and

orthoborates of polyhydric alcohols. Organoboron

compounds include B–N compounds, because B–N

is isoelectronic with C–C.

Boron Speciation

0004Boric acid is an exclusively monobasic acid and is not

a proton donor, but rather accepts a hydroxyl ion (a

Lewis acid) to form the tetrahedral anion B(OH)



(eqn (1)):

BðOHÞ

þ 2H

O $ H

þ BðOHÞ



¼ 9:25ð25



CÞ: ð1Þ

0005At typical physiological boron concentrations

(6.0 10

7

– *9.0 10

3

mol l

1

) in plants, animals

(Table 1), or humans, inorganic boron is essentially

present only as the mononuclear species boric acid

B(OH)

and as borate B(OH)



. Within the normal pH

range of the gut and kidney, B(OH)

would prevail

as the dominant species (pH 1: *100% B(OH)

;

pH 9.3: 50%; pH 11: *0%). Undissociated (and

uncharged) boric acid is very soluble in water

(B[OH]

-saturate solution at 20



C ¼0.75 mol l

1

)

and has a high lipid solubility of the same order as

urea. Polyborate species can form near neutral

physiological conditions (pH *7.4) when borate

concentrations exceed *0.025 mol l

1

, an unusually

high boron concentration in biological systems, but

still lower than that found in the snap bean leaf

(0.1 mol l

1

0006The speciation of boron in foods has not been

determined, but if plant and animal boron absorption

mechanisms are analogous, the organic forms of

boron per se are probably unavailable. However, the

strong association between boron and polyhydroxyl

ligands (described below) is easily and rapidly re-

versed by dialysis, change in pH, heat, or the excess

addition of another low-molecular-weight polyhy-

droxyl ligand. Thus, within the intestinal tract, most

ingested boron is probably converted to B(OH)

, the

normal end product of hydrolysis of most boron

compounds.

Boron Isotopes

0007The study of boron kinetics in biological systems is

hampered because the radioisotopes

B, and

all have half-lives of less than 1 s. However, two stable

boron isotopes,

B and

B, are distributed unequally

in nature (19.8 and 80.2%, respectively). This

phenomenon has been successfully exploited to

determine boron translocation in plant species and

boron kinetics in animal models of human physi-

ology. The

boron has a very large cross-section for

thermal-neutron capture, and this property has been

566 BORON

used in neutron capture therapy (NCT) for inoperable

brain tumors. During NCT, a boronated compound,

preferentially bound to the tumor cells, is irradiated

with thermal neutrons. Following neutron capture,

the energy is released as a g ray, a particle and lithium

nucleus, the latter two traveling 9 and 5 mm, res-

pectively. Thus, heavily ionizing radiation is de-

posited in single targeted cells with minimal

collateral damage.

Boron Biochemistry

Boron Esters

0008Boroester formation Boroesters result from reac-

tions between boron oxo compounds and certain

mono or polyhydroxy compounds to form specific

organoboron complexes. Boroesters probably repre-

sent the most biologically relevant boron species be-

cause of the vast number of biomolecules that contain

one or more hydroxy groups with suitable positions.

Boric acid reacts with suitable dihydroxy compounds

to form the corresponding boric acid monoesters

(‘partial’ esterification) (e.g., Figure 1) that retain

the trigonal–planar configuration and no charge.

0009A borate monoester (‘partial’ esterification; mono-

cyclic) (Figure 2) with a tetrahedral configuration and

a negative charge is created when borate forms a

complex with a suitable dihydroxy compound. A

compound of similar configuration and charge is

also formed when a boric acid monoester forms a

complex with an available hydroxyl group. These

two types of boromonoesters can react with another

dihydroxy compound to give a corresponding spiro-

cyclic borodiester (‘complete’ esterification) that is a

chelate complex with a tetrahedral configuration and

negative charge (Figure 3). Boric acid and boric acid-

like structures, instead of borate, are most likely the

reactive species with biological ligands, because it is

probably easier for a diol to substitute for a relatively

loosely bound water molecule associated with boric

acid or a boric acid-like structure than it is for the diol

to substitute for a hydroxyl ion in borate or a borate-

like structure.

tbl0001 Table 1 Concentration of boron in selected foods (wet-weight)

Food Micrograms

per100 g

Animal products

Milk, low fat, 2% milkfat 27.0 + 3.0

Chicken, fryer, light meat, cooked with meat

and skin, flour, with added fat

12.0 + 2.0

Beef, ground, cooked, pan-fried 9.0 + 2.0

Butter, with salt 4.0 + 0.0

Cereal grain products

Cornbread, homemade-type 56.0 + 4.0

Cereal, ready-to-eat, wheat, shredded 34.0 + 2.0

Bread, white, enriched 17.0 + 1.0

Rice, white, long-grain, instant, enriched 9.0 + 0.0

Macaroni, cooked, enriched, with salt 8.0 + 1.0

Sweeteners/catsup

Jelly, grape 145.0 + 8.0

Catsup 100.0 + 14.0

Sugar, white, granulated 10.0 + 1.0

Infant foods

Fruit, prunes with tapioca 359.0 + 8.0

Carrots and beef, strained 132.0 + 9.0

Vegetable, corn, creamed, strained 19.0 + 2.0

Infant formula, Gerber, with iron 12.0 + 0.0

Fruits and fruit beverages

Avocado, raw 14 300.0 + 42.0

Grape juice, unsweetened 342.0 + 2.0

Cherries, sweet, raw 228.0 + 3.0

Pears, raw 227.0 + 11.0

Apple, juice, bottled, unsweetened 190.0 + 3.0

Peach, raw 171.0 + 7.0

Orange juice, unsweetened, reconstituted

from concentrate

81.0 + 1.0

Pineapple juice, canned 78.0 + 1.0

Vegetables

Snacks, potato chips, plain, salted 228.0 + 6.0

Squash, winter, cooked, baked 161.0 + 10.0

Carrots, raw 130.0 + 7.0

Radishes, raw 66.0 + 11.0

Potato, boiled, cooked without skin 48.0 + 2.0

Beverages

Alcoholic beverage, wine, table, white 364.0 + 3.0

Coffee, instant, regular, prepared with water 24.0 + 0.0

Carbonated beverage, cola, contains caffeine 10.0 + 0.0

Tea, leaf, brewed in a porous bag 6.0 + 0.0

Water, spring, bottled 2.0 + 0.0

Data from Meacham and Hunt (1998).

Mean + standard deviation (n ¼ 3) of values from a single package of a

single lot of a single brand.

BOH

(CH

)

fig0001Figure 1 Structure I.

(CH

)

fig0002Figure 2 Structure II.

(CH

)

(CH

)

fig0003Figure 3 Structure III.

BORON 567

0010 Ligand structure Ligands that contain adjacent and

cis hydroxyl groups are those most likely to react with

boron oxo compounds to give a boroester, and the

reactivity of boric acid with the ligand generally

increases as the number of these cisoid groups in-

creases. The relevant cis-diol conformations for

boron complexation are present in several biologic-

ally important sugars, their derivatives (sugar

alcohols, -onic, and -uronic acids), and some poly-

mers. Common examples include mannitol, ribose,

erythrose, and glycerol. Sugars often form intramo-

lecular hemiacetals in water where those with five-

membered rings are called furanoses, and those with

six-membered rings are called pyranoses. Com-

pounds in a configuration where there are cis-diols

on a furanoid ring (e.g., ribose, apiose, and erythri-

tan) are rare in nature and form stronger complexes

with boron than do compounds configured to have

cis-diols predominately on a pyranoid ring (e.g., the

pyranoid form of a-d-glucose). Glucose is virtually all

in the pyranose form. The pyridine (e.g., NAD

NADP) and flavin (e.g., FAD) nucleotides have re-

ceived special attention, because they contain a ribose

moiety with a cisoid diol conformation.

0011 pK

Because borate complexes often have a much

lower pK

(e.g., boron-mannitol, 5.2) than free boric

acid (9.25), the pK

of many boron complexes is

considerably below the physiological pH. This phe-

nomenon has functional consequences and becomes

the mechanism of action for some enzymatic activ-

ities. For example, boric acid is a competitive inhibi-

tor of Streptomyces griseus Protease 3, and there is

decreased affinity of the protein for boric acid below

pH 7.0. This is directly attributable to the stability of

the enzyme inhibitor complex, which is dependent on

an ionizing group in the protein with an apparent pK

of 6.6. This finding indicates that boric acid is an

inhibitor of the enzyme at physiological pH by

shifting the pK

Boron–Nitrogen Compounds

0012 The known ability of boron to form covalent bonds

with the nitrogen atom of amine groups and the

observation that boron binds near the coordinating

iron site of hemerythrin (the nonheme iron-contain-

ing, oxygen transport protein of the sipunculid worm,

Golfingia gouldii) suggest that a large array of bio-

compounds other than polyols can react with boron

to form complexes. For example, there is experi-

mental evidence to suggest that the mechanism for

inhibition of a sub-subclass of enzymes (the serine

proteases) by boron involves the formation of a cova-

lent bond between boron and a specific nitrogen at

the active site of these enzymes (Figure 4).

Boron Occurrence in the Environment

Anthropogenic Sources

0013Each year, coal combustion is estimated to release

between 28 000 and 330 000 tonnes of boron to the

atmosphere and between 24 000 and 287 000 tonnes

of boron go to landfill/soil. Also, approximately

300 000 tonnes of boron are recovered from ex-

tracted and refined deposits destined for five main

product groups: insulation fiberglass/textile fiber-

glass/borosilicate glass (39%), ceramics (13%), deter-

gents (19%), fertilizers (5%), cellulose insulation

(2%), and other products (23%) including nuclear

shielding, leather tanning, and catalysis. Boron, in

the form of borax, has been used since Egyptian and

Roman times for the preparation of hard (borosili-

cate) glasses. Boron leaches readily from most glass-

ware, especially under conditions of alkalinity.

Soil

0014The largest single natural deposit of boron is located

at Boron, California, an area of former volcanic ac-

tivity and associated with the waters of former hot

springs. Within geological boron deposits, boron is

usually present as a borate mineral such as borax,

(OH)

8H

O. A 1956 survey of US soils

indicated an average total boron content of 30 mg

1

. Less than 5% of the total soil boron is available

for crop uptake and depends on release from soil

minerals, mineralization from decomposed organic

matter, artificial addition to soils by irrigation or

fertilization, and subsequently distribution between

the solid and liquid phases of the soil. Boron is easily

leached out of soils by rainwater. Thus, plant boron

deficiency is of concern in humid regions with light-

textured, acid soils.

Water

0015Weathering of clay-rich sedimentary rock is the major

source of total boron mobilized into the aquatic

environment, although sewage effluent can be an

important source of boron, especially in areas

where boron compounds are major constituents of

detergent products. Undissociated boric acid is the

Asp

102

His

Ser

195

−

fig0004Figure 4 Structure IV.

568 BORON

predominant species of boron in most natural fresh-

water systems. The concentration of boron in surface

water may vary substantially between geographic

locations and water sources (values in mgml

1

;in

parentheses, mmol ml

1

): UK, 0.046–0.822 (0.004–

0.077); Italy, 0.400–1.00 (0.037–0.093); the USA,

0.001–5.0 (0.00009–0.467). The concentration of

boron in seawater is 4.5 mgml

1

(0.42 mmol ml

1

whereas the median boron concentration in USA

drinking water is 0.031 mgml

1

. Thus, the usual

boron intake through drinking water is usually not

high. For example, an adult consuming 2 l of water

with the median concentration and ingesting 1.5 mg

of boron in the diet would be exposed to < 1.6 mg or

< 10% of the acceptable reference dose (18 mg of

boron per day).

Foods

0016 Boron is unequally distributed within Angiospermae,

the class of plants most often utilized in human and

animal diets. Most species within the subclass Dico-

tyledoneae, which includes fruits, vegetables, tubers

and legumes, have much higher concentrations of

boron than do species in the subclass Monocotyledo-

neae, especially gramineaceous species (the grasses),

i.e., rice, corn, rice, and wheat (Table 1). Foods

cooked in boiling water are quickly leached of

boron content. Also, B(OH)

is volatile in steam.

Boron loss could conceivably be further enhanced

during pressure cooking with chlorinated or fluorin-

ated water; boron–halogen compounds are extremely

volatile at high temperatures.

0017 Estimated daily intakes of boron vary with age and

sex. Infants, toddlers, adolescent females and males,

adult females and males, and senior females and

males in the USA consume 0.545, 0.534, 0.590,

0.848, 0.698, 0.907, 0.731, and 0.863 mg of boron

per day, respectively. The concentration of elemental

boron in animal muscle and milk is relatively low.

Because whole milk (0.29 mg of boron per gram) is

consumed in such large quantities, it is the typical

primary source of boron for infants, toddlers, and

adolescents. Coffee is the primary source of boron

for adult females and males, and senior females and

males in the USA. There is a close relation between

boron and vitamin intakes; a diet low in boron is

typically low in vitamins, especially ascorbic acid.

Boron Essentiality and Function

0018 The high affinity of boric acid for adjacent and cis-

hydroxyl groups present on biomolecules may have

exerted evolutionary pressure to select for carbohy-

drate energy sources with low percentages of the

furanose forms described above. Conversely, there

may have been selection for two natural sugars,

apiose and ribose, because their physiological deriva-

tives have a strongly borate-complexing furanose

configuration and they serve as components of im-

portant structural or enzyme-related biomolecules, as

described below.

Prokaryotes

0019Boron essentiality for the heterocystous Cyanobac-

teria, predominant organisms during the Middle

Pre-Cambrian Period, indicates that boron was an

essential element during the early evolution of life.

Boromycin, an antibiotic from Streptomyces antibio-

ticus, was the first well-defined boron-containing bio-

logical organic compound. Antibiotics with a similar

structure are excreted by a marine isolate belonging

to Streptomyces griseus (aplasmomycin) and from the

myxobacterium Sorangium cellulosum (tartrolon B;

Figure 5). These antibiotics are ionophoric macro-

lides and have four inward directed oxygen atoms

(two cis-hydroxyl groups) that provide an ideal geom-

etry for accommodation of the boron atom and thus

formation of a stable borodiester.

Plants

0020Whether certain lower plants lack a boron require-

ment is being revisited. Findings in 1999 that boron

stimulated growth in the fungus Saccharomyces cere-

visiae (a yeast) supplanted findings in 1968 to the

contrary. There is a demonstrated boron requirement

for Penicillium italicum but apparently not for the

fungi Neurospora crassa or Aspergillus niger. Boron

stimulated penicillin production, but not growth,

in Penicillium chrysogenum, and boron enhanced

growth of Chlorella vulgaris, but no apparent boron

requirement has been demonstrated among the many

species of chlorophyta tested. At least 16 species of

−

fig0005Figure 5 Structure V.

BORON 569

marine and eight species of freshwater diatoms and

some species of marine algal flagellates have an

absolute boron requirement.

0021 All vascular plants have acquired a unique require-

ment for boron. However, the primary role and mode

of action of boron remain controversial. Boron seems

to be involved in such diverse cellular processes as

sugar transport, cell-wall synthesis, lignification, cell-

wall structure, carbohydrate metabolism, RNA me-

tabolism, respiration, indole acetic acid metabolism,

phenol metabolism, and membranes. Rhamnogalac-

turonan-II (RG-II) is a small, structurally complex

polysaccharide of the pectic fraction of primary

plant cell walls. It is present in at least 24 plant species

and represents an extreme example of the evolution-

ary conservation of wall polysaccharide structure.

RG-IIs contain the unusual monosaccharide apiose

described above and an atom of boron that cross-

links two RG-II dimers at the site of the apiose resi-

dues to form a borodiester (Figure 6). Knowledge that

borate ester cross-linking of polysaccharides in vitro

is pH-dependent has led to the suggestion that the

boron cross-links in RG-II are the ‘load-bearing,’

acid-labile linkages that are hydrolyzed by a decrease

in wall pH during auxin-induced cell expansion.

However, graminaceous plants, with an absolute but

low requirement for boron, have very low amounts of

boron, pectin, and complexable polysaccharides in

their cell walls, a finding that suggests unknown

additional roles for the element.

Humans and Animal Models

0022Boron homeostatic control Gastrointestinal ab-

sorption of inorganic boron and subsequent urinary

excretion are near 100%. In humans, a lack of boron

accumulation and relatively small changes in blood

boron values during a substantial increase in dietary

boron support the concept of boron homeostasis.

Female rats given water high in boron (9.25 mmol

1

) for 21 days exhibited increased plasma boron

concentrations, although some type of homeostatic

mechanism concurrently eliminated any excess of

boron from two examined organs, liver and brain,

against their own concentration gradients. In cows,

the percentage of filtered boron reabsorbed by the

kidneys decreased significantly with increased boron

intake, a finding that suggests physiologic regulation

of the element.

0023Boron and reproduction Boron may be essential for

embryological development in at least two separate

vertebrate phylogenetic classes. In the South African

clawed frog, Xenopus laevis, dietary boron depriv-

ation (4.16 mmol kg

1

) causes a high proportion of

necrotic eggs, fertilized eggs with a high frequency

of abnormal gastrulation, and abnormal development

of the gut, craniofacial region, and eye; visceral

edema; and kinking of the tail musculature and noto-

chord. In mated zebrafish (Danio rerio) fed boron-

depleted brine shrimp and maintained in low-boron

water (0.1 mmol l

1

), the boron content of the

blastulas was only 5% of that in blastulas from

boron-supplemented (45.0 mmol l

1

) parents. The

early cleavage stage of development was the most

sensitive to boron deficiency, although repletion of

low-boron embryos during the first hour after fertil-

ization rescued them from death.

0024Boron and cartilage and bone structure Interest in

mammalian boron nutrition was renewed after a

36-year hiatus with the discovery that boron supple-

mentation of a boron-low diet reduced gross bone

abnormalities in the vitamin D-deficient chick model

system. Other subsequent findings at the microscopic

level indicated that physiologic amounts of boron

(321 mmol kg

1

) function to modify mineral metabol-

ism in vitamin D deficiency (3.13 mgkg

1

) by sup-

pressing initiation of growth cartilage mineralization

in magnesium deficiency and enhancing cartilage cal-

cification in magnesium adequacy (see Figure 7). The

effects of boron in this model on cartilage calcifica-

tion apparently are beneficial in both magnesium

deficiency and adequacy because the vitamin D defi-

ciency-induced mortality was substantially reduced

by dietary boron. Furthermore, supplemental boron

fig0006 Figure 6 Structure VI.

570 BORON

alleviated distortion of the marrow sprouts, a distor-

tion characteristic of vitamin D deficiency.

0025 Boron also has an apparent undefined role in meta-

bolic events not directly related to extracellular matrix

calcification. In ovo injections of boron (90 mmol)

or 1-25-dihydroxycholecalciferol reduced the abnor-

mal height of the growth plate of 1-day-old chicks

hatched from vitamin D-deficient eggs. In addition,

physiological supplements of boron (130 mmol kg

1

)

to a boron-low diet (16 mmol kg

1

) increased chon-

drocyte density in the proliferative zone of the growth

plate in vitamin D-deficient chicks.

0026Boron and mineral metabolism In postmenopausal

volunteers fed marginal amounts of magnesium

(4.5 mmol per day), boron supplementation (280 mmol

per day) of the low-boron diet (33 mmol per day)

significantly decreased the percentage of dietary

calcium lost in the urine (1.4%) but significantly

increased that percentage (2.5%) in volunteers fed

(a) (b)

ICC

100 µm

fig0007 Figure 7 Microphotographs (all at same magnification) depicting marrow sprout (MS) orientation and initiation of cartilage calcifica-

tion (ICC) in the chick proximal tibial epiphysial plate. ICC beyond a frame is denoted by slashed arrows. Boron supplementation

corrected the cholecalciferol-deficiency-induced disorientation of the MS (compare a and b, and c and d). ICC is inhibited by boron in

magnesium inadequacy (compare a and b), but enhanced in magnesium adequacy (compare c and d). Dietary supplements (milligrams

of supplement per kilogram of diet): (a) B, 0; Mg, 300; (b) B, 3; Mg, 300; (c) B, 0; Mg, 500; (d) B, 3; Mg, 500. Data from Hunt (1989).

BORON 571

ample amounts of magnesium (14.0 mmol per day), a

relation that may be important in understanding

metabolic mineral disorders that perturb calcium

balance. A similar phenomenon occurred in either

free-living sedentary or athletic premenopausal

women consuming self-selected typical Western diets

not different in analyzed calcium content; boron sup-

plementation (280 mmol per day) increased urinary

calcium loss. In a different study of older volunteers

fed a low-magnesium (4.73 mmmol 8330 kJ

1

), mar-

ginal copper (25.3 mmol 8330 kJ

1

) diet (men, and

women on or not on estrogen therapy), boron reple-

tion (300 mmol 8330 kJ

1

) after boron depletion

(21.3 mmol 8330 kJ

1

) significantly decreased calcito-

nin and significantly increased ionized calcium, but

not total calcium concentrations in serum in a manner

similar to that caused by estrogen therapy. In the

vitamin D-deficient rat model fed a low-boron diet,

supplemental dietary boron enhanced the apparent

absorption and retention of calcium and phosphorus

and increased femur magnesium concentrations.

0027 Boron and steroid metabolism There is clear evi-

dence that dietary boron affects steroid metabolism.

In particular, circulating concentrations of vitamin D

metabolites are sensitive to boron nutriture. The

number of vitamin D-deficient chicks with detectable

serum concentrations of 25-hydroxycholecalciferol

and the overall serum concentrations of 25-hydroxy-

cholecalciferol increased when boron-deprived chicks

(15 mmol B kg

1

) were supplemented with physio-

logical amounts of boron (280 mmol kg

1

). In the

same study, physiological supplements of boron

improved growth, feed efficiency, leg conditions,

and bone calcium, and serum ionized calcium in

broiler chicks fed low amounts of vitamin D, but

not in vitamin D-deprived or adequate chicks. These

findings indicate that dietary boron enhances the effi-

cacy of vitamin D but cannot substitute for the vita-

min. Further research is needed to determine whether

boron enhances vitamin D absorption or increases

cholecalciferol hydroxylase activity. In volunteers

(men, and women on or not on estrogen therapy),

boron supplementation after consumption of a low

boron diet increased serum 25-hydroxycholecalci-

ferol (62.4 + 7.5 vs. 44.9 + 2.5 mmol l

1

, mean +

SEM), an effect that may be especially important

during the winter months when those concentrations

normally range between 35 and 105 mmol l

1

0028 The circulating concentrations of 17b-estradiol also

respond to boron nutriture. Perimenopausal women

who excreted < 93 mmol of boron per day during the

placebo period exhibited increased serum concentra-

tions of estradiol after boron supplementation

(231 mmol of boron per day) of self-selected diets. In

a separate study, postmenopausal women on estrogen

therapy, but neither men nor postmenopausal women

not ingesting estrogen, also exhibited increased serum

concentrations of estradiol after boron supplementa-

tion (280 mmol of boron per day) of a low boron diet

(23 mmol of boron 8330 kJ

1

). However, plasma estra-

diol, but not testosterone, concentrations increased in

young male volunteers when their self-selected diets

were supplemented with ample amounts of boron

(10 mg per day).

0029Boron and enzyme regulation Boron influences the

activities of at least 26 enzymes examined (various

oxidoreductases, transferases, hydrolases, and iso-

merases), most often in an inhibitory manner, by bind-

ing to cofactors (e.g., NAD) or substrates, or by

unknown mechanisms. Reversible enzymatic inhib-

ition as an essential role for an element is unusual.

However, there is irrefutable evidence that boron

serves to inhibit or dampen several metabolic path-

ways in higher plants. A serious outcome of boron

deficiency in plants is starch accumulation, a condi-

tion thought to be caused by increased activity of

an enzyme in that pathway, starch phosphorylase.

Oxidoreductase enzymes that require pyridine (e.g.,

NAD

or NADP) or flavin (e.g., FAD) nucleotides (EC

1.1.1, 1.1.3, 1.2.1, 1.3.5, 1.6.2) are competitively in-

hibited by borate or its derivatives as boron competes

for the NAD or flavin cofactor. The serine proteases

(EC 3.4.21) represent one critical sub-subclass of

hydrolases that have many essential regulatory roles

including the blood coagulation system (e.g., coagula-

tion Factor Xa). Boron reversibly inhibits the activity

of these enzymes by serving as a transition-state

analog. It is possible that boron acts as an unobtrusive

metabolic regulator by quenching the activity of some

enzymes and/or stabilizing reactive compounds to

limit the hyperactivity of several physiological systems

including the normal inflammatory response.

0030Boron and membrane function There are numerous

indications that boron is important for membrane

function. The esterification reaction that produces

boromonoesters (e.g., Figure 1 or 2) is easily revers-

ible, because these esters are completely hydrolyzed

when transferred into water. Therefore, it is reason-

able that boromonoesters in the hydrophobic envir-

onment of the lipid portion of the plasmalemma

should have a prolonged functionality, because the

absence of water in these environments shifts the

equilibrium to the right (eqn (2)).

BðOHÞ

þ 3ROH $ BðORÞ

þ 3H

O: ð2Þ

0031Heterocystous cyanobacteria may require boron

interactions with polyhydroxy components of the

572 BORON

cellular membrane to maintain efficient conformation

of cell membranes and thus preservation of the anaer-

obic environment of the heterocyst. Very early re-

search on plant boron nutrition indicated that boron

deficiency caused a reduction in ion uptake in Impa-

tiens balsamina, and considerable evidence has accu-

mulated since then that boron is involved in

plasmalemma-bound transport processes for higher

plants and diatomaceous species. Low-boron zebra-

fish zygotes began to die during the one-cell stage

where blebbing of the cell and yolk-sac membranes

marked the early stages of death followed by extrusion

of cytoplasm and yolk-sac contents. In boron-deprived

rats, increases in dietary potassium from marginally

deficient to adequate to luxuriant induced increases in

the transport of calcium into thrombin-activated

platelets. However, physiological amounts of boron

muted the effect of potassium on calcium transport.

Boron may have reacted directly with thrombin to

somehow modify platelet activation because thrombin

is a serine protease inhibited by boron. However, these

findings are similar to those expected for plasma-

lemma ion transport involving regulation of the

voltage-dependent Ca

2þ

channel by boron through

inhibition of NADPH or cAMP concentrations.

0032 Boron and immune function There is evidence that

dietary boron helps control the normal inflammatory

process. The antigen-induced arthritis rat model ex-

hibited reduced paw swelling and circulating neutro-

phil concentrations when fed with physiological

amounts of boron (190 mmol kg

1

). Commercial rat

chow contains considerable higher amounts of

boron (*1100 mmol kg

1

). Perimenopausal women

excreted 110 and 304 mmol of boron per day during

the placebo and boron supplementation periods, re-

spectively, and exhibited an increased percentage of

polymorphonuclear leukocytes during the boron sup-

plementation period. Boron-containing rhamnoga-

lacturonan-II from Panax ginseng leaves enhanced

expression of the Fc receptor (that internalizes anti-

gen–antibody complexes) and interleukin-6 (IL-6)

production activity of mouse macrophages. Dietary

boron may serve as a signal suppressor that down-

regulates specific enzymatic activities typically ele-

vated during inflammation at the inflammation site.

Suppression, but not elimination, of these enzyme

activities by boron is hypothesized to reduce the inci-

dence and severity of inflammatory disease.

Boron Toxicity

0033 As with all other elements, boron produces toxicity

in all tested biological organisms when excessive

amounts are absorbed. The associated toxicity of

boric acid when used as an antiseptic in lieu of anti-

biotics on abraded epithelium (i.e., surgical wounds

and diaper rash) was overlooked for many years, even

though signs of poisoning were reported soon after its

introduction into clinical use. Boron is more of a

bacteriostat than a bactericide and as such is not

sufficient for most modern usage. The minimum

lethal dose of boron for humans has not been estab-

lished, although single doses of 18–20 g in adults have

been fatal. Signs of acute boron toxicity, regardless of

route of administration, include nausea, vomiting,

headache, diarrhea, erythema, hypothermia, restless-

ness, weariness, desquamation, renal injury, and

death from circulatory collapse and shock. Autopsy

may reveal congestion and edema of brain, myocar-

dium, lungs, and other organs, with fatty infiltration

of the liver. Chronic boron toxicity symptoms include

poor appetite, nausea, weight loss, decreased sexual

activity, seminal volume, sperm count and motility

and increased seminal fructose. At present, death

from boron poisoning is exceptionally rare probably

because of the emphasis placed on maintaining the

electrolytic balance and supporting kidney function

during the worst part of the illness. Depending upon

boron blood levels, treatment ranges from observa-

tion to gastric lavage to dialysis.

See also: Bone; Enzymes: Functions and Characteristics;

Hormones: Steroid Hormones; Immunology of Food