boron is essential for all higher plants in
phylogenetic kingdom Viridiplantae
(1) and at least some organisms in the phylogenetic kingdoms Eubacteria (2),
Stramenopila (3), and Animalia (4,5). Specific species in
the kingdom Fungi have a demonstrated physiological
response to boron, an important finding because Fungi
species are thought to share a common ancestor with animals
exclusive of plants (6). Physiologic concentrations of
the element are needed to support metabolic processes in
several species in Animalia. For example, embryological
development in fish and frogs does not proceed normally
in the absence of boron. There is evidence that higher vertebrates,
that is, chicks, rats, and pigs require physiological
amounts of boron to assist normal biologic processes including
immune function, bone development, and insulin
regulation. In humans, boron is under apparent homeostatic
control and is beneficial for immune function and
calcium and steroid metabolism.
COMMON CHEMICAL FORMS
Boron is the fifth element in the periodic table with a
molecular weight of 10.81 and is the only nonmetal in
Group III. Organoboron compounds are those organic
compounds that contain B–O bonds, and they also include
B–N compounds, because B–N is isoelectronic with
C–C (7). Organoboron compounds are apparently important
in biological systems and are the result of interaction
with OH or amine groups. Organoboron complexes occur
in plants and are produced in vitro with biomolecules
isolated from animal tissues (8).
Boron does not naturally occur free nor bind directly to
any element other than oxygen except for trivial exceptions,
for example, NaBF4 (ferrucite) and (K,Cs)BF4 (avogadrite)
(7). Its average concentration in the oceans is
4.6mg/Land is the 10th most abundant element in oceanic
salts (9). Weathering of clay-rich sedimentary rock is the
major source of total boron mobilized into the aquatic environment
(10). Undissociated boric acid (orthoboric acid)
is the predominant species of boron in most natural freshwater
systems (10) where most concentrations are below
0.4 mg/L and not lowered by typical treatments for drinking
water. The most common commercial compounds
of boron are anhydrous, pentahydrate, and decahydrate
(common name: tincal) forms of disodium tetraborate
(borax, Na2B4O7), colemanite (2CaO°§3B2O3°§5H2O), ulexite
(Na2O°§2CaO°§5B2O3°§16H2O), boric acid (H3BO3), and
monohydrate and tetrahydrate forms of sodium perborate
Inorganic boron, within the concentration range
expected for human blood (2–61 M B; 22–659 ng
B/g wet blood) (12), is essentially present only as the
monomeric species orthoboric acid (common name: boric
acid) B(OH)3 and borate, that is, B(OH)4
− (13). Boric acid
is an exclusively monobasic acid and is not a proton donor,
but rather accepts a hydroxyl ion (a Lewis acid) and leaves
an excess of protons to form the tetrahedral anion B(OH)4
+ 2H2O ⇔ H3O+ + B (OH)−
4 pKa = 9.25(25◦C)
Within the normal pH range of the gut and kidney,
B(OH)3 would prevail as the dominant species (pH 1:
∼100% B(OH)3; pH 9.3: 50%; pH 11: ∼0%) (15).
Many biomolecules contain one or more hydroxy groups
and those with suitable molecular structures can react with
boron oxo compounds to form boosters, an important
class of biologically relevant boron species. Several types
of boron esters exist. Boric acid reacts with suitable dihydroxy
compounds to form corresponding boric acid monoesters
(“partial” esterification) (Fig. 1) that retain the
trigonal-planar configuration and no charge.
In turn, a boric acid monoester can form a complex
with a ligand containing a suitable hydroxyl to create
a borate monoester (“partial” esterification; monocyclic)
(Fig. 2), but with a tetrahedral configuration and a negative
charge. A compound of similar configuration and
charge is also formed when borate forms a complex
with a suitable dihydroxy compound. The two types
of boro monoesters can react with another suitable dihydroxy
compound to give a corresponding spirocyclic
borodiester (“complete” esterification) that is a chelate
Figure 1 Boric acid may complex with a suitable dihydroxy ligand to form
a boric acid monoester (“partial” esterification) that retains a trigonal-planar
configuration and no charge. Borate may complex with a suitable dihydroxy ligand to form
a borate monoester (“partial” esterification; monocyclic) with a tetrahedral
configuration and a negative charge.
complex with a tetrahedral configuration and negative
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 charged hydroxyl ion in borate
or a borate-like structure (16).
Boron is an integral component of several biomolecules
in which it is thermodynamically stabilized in a covalent
bond (17–20) or by forming a boroester (21). Its presence in
these molecules is essential; in its absence, they no longer
perform their normal physiologic functions. Of great interest
is a boron-containing biomolecule produced by a bacterium
that is not an antibiotic but rather a cell-to-cell communication
signal (20). Communication between bacteria
is accomplished through the exchange of extracellular signaling
molecules called autoinducers (AIs). This process,
termed “quorum sensing,” allows bacterial populations
to coordinate gene expression for community cooperative
processes such as antibiotic production and virulence factor
expression. AI-2 is produced by a large number of bacterial
species and contains one boron atom per molecule.
Not surprisingly, it is derived from the ribose moiety of
biomolecule, (S)-adenosylmethionine (SAM). The gliding
bioluminescent marine bacterium, Vibrio harveyi (phylum
Proteobacteria), produces and also binds AI-2. In V. harveyi,
the primary receptor and sensor for AI-2 is the protein
LuxP, which consists of two similar domains connected by
a three-stranded hinge. The AI-2 ligand binds in the deep
cleft between the two domains to form a furanosyl borate
diester complex (Fig. 4) (20).
Boron is a structural component of certain antibiotics
produced by certain myxobacteria, a distinct and unusual
group of bacteria. For example, tartrolon B (Fig. 5)
is characterized by a single boron atom in the center of the
Figure 3 Boric acid monoesters or borate monoesters can combine with a
suitable dihydroxy compound to form a corresponding spirocyclic borodiester
[“complete” (add the close parenthesis) esterification] that is a chelate
complex with a tetrahedral configuration and negative charge.
Figure 4 The autoinducer, AI-2, with its integral boron atom is stabilized
by a hydrogen network in the binding site of the receptor. The O–O or O–N
distances for potential hydrogen bonds are shown in angstroms. Source: From
molecule (18). Another related antibiotic, boromycin, was
discovered to be potent against human immunodeficiency
virus (HIV) (22). It strongly inhibits the replication
of the clinically isolated HIV-1 strain and apparently, by
unknown mechanisms, blocks release of infectious HIV
particles from cells chronically infected with HIV-1.
Animal and Human Tissues
Only meager information is available on the speciation of
boron in animal or human tissues. However, animal and
human biocompounds with vicinal cis-diol moieties bind
Figure 5 Tartrolon B, an example of certain antibiotics produced by certain
myxobacteria that require the presence of a single atom of boron for
Experimental data indicate that biochemical species with vicinal cis-diols bind strongly to boron: (S)-adenosylmethionine (SAM) ≡ diadenosine
hexophosphate (Ap6A) ≡ Ap5A > Ap4A > Ap3A ≡ NAD+ > Ap2A > NADH ≡ 5ATP > 5ADP > 5AMP > adenosine (ADS). Species without these moieties
do not bind boron well: 3AMP ≡ 2AMP ≡ cAMP ≡ adenine (ADN).
boron; those without these moieties typically do not. Of
these animal or human biocompounds examined, SAM
has the highest known affinity for boron (8). It is the predominant
methyl donor in biological methylations and is
therefore a versatile cofactor in various physiologic processes.
NAD+, an essential cofactor for five sub-subclasses
of oxidoreductase enzymes, also has a strong affinity
for boron (23). The di-adenosine-phosphates (ApnA) are
structurally similar to NAD+. Boron binding by Ap4A,
Ap5A, and Ap6A is greatly enhanced compared with
NAD+ but is still less than that of SAM (8). The ApnA
molecules are present in all cells with active protein synthesis
and reportedly regulate cell proliferation, stress response,
and DNA repair (24). At physiologic pH, the adenine
moieties ofApnAare driven together by hydrophobic
forces and stack interfacially (25). Stacking of the terminal
adenine moieties brings their adjacent ribose moieties
into close proximity, a phenomenon that apparently potentiates
cooperative boron binding between the opposing
All higher plants require boron and contain organoboron
complexes. There may have been considerable evolutionary
pressure exerted to select for carbohydrate energy
sources that do not interact with boron. Sugars often form
intramolecular hemiacetals: those with five-membered
rings are called furanoses and those with six-membered
rings are called pyranoses. In cases where either five- or
six-membered rings are possible, the six-membered ring
usually predominates for unknown reasons (26). In general,
compounds in a configuration in which there are
cis-diols on a furanoid ring (e.g., ribose, apiose, and erythritan)
form stronger complexes with boron than do those
configured to have cis-diols predominately on a pyranoid
ring (e.g., the pyranoid form of -D-glucose). D-Glucose
reacts with boric acid (27) but the near absence (<0.5%)
of an -furanose form of D-glucose in aqueous solutions
(26) suggests that glucose was selected as the aldose for
general energy metabolism because of its lower reactivity
with boric acid. On the other hand, ribose may have
been selected as part of the chemistry of nucleic acid and
nucleotide function and apiose for, rather than against, its
extraordinary borate-complexing capability.
Recent evidence suggests that the predominant
place of boron function in plants is in the primary cell
walls where it cross-links rhamnogalacturonan II (RG-II)
(Fig. 7), a small, structurally complex polysaccharide of the
pectic fraction. RG-IIs have an atom of boron that crosslinks
two RG-II dimers at the site of the apiose residues
to form a borodiester (28). However, this function is not
adequate to explain all boron deficiency signs in plants.
Twenty-six boron-binding membrane-associated proteins
were identified recently in the higher plant, Arabidopsis
thaliana (29), and boron oxo compounds also form stable
ionic complexes with the polyol ligands mannitol, sorbitol,
and fructose in liquid samples of celery phloem sap
and vascular exudate and phloem-fed nectaries of peach
Boron speciation in dietary supplements varies widely
(31) as does the relevant information provided by various
dietary supplement manufacturers. It is sometimes listed
only in a general manner (e.g., “borates” or “boron”),
and occasionally in a more specific manner (e.g., “sodium
Schematic representation of two monomers of the pectic polysaccharide
rhamnogalacturonan-II cross-linked by an atom of boron at the site
of the apiose residues to form a borodiester. Multiple cross-links form a
supramolecular network. Source: From Ref. 75.
borate” or “sodium tetraborate decahydrate”). Several
commercially available forms (e.g., “boron amino acid
chelate,” “boron ascorbate,” “boron aspartate,” “boron
chelate,” “boron citrate,” “boron gluconate,” “boron glycerborate,”
“boron glycinate,” “boron picolinate,” “boron
proteinate,” “boron bonded with niacin,” and “calcium
fructoborate”) are not well characterized in the scientific
literature. Most often, dietary boron supplements are provided
in conjunction with other nutrient supplements.
BIOAVAILABILITY, EXCRETION, AND HOMEOSTASIS
If plant and animal boron absorption mechanisms are
analogous, the organic forms of the element per se are
probably unavailable (32). However, the strong association
between boron and polyhydroxyl ligands (described
later) is easily and rapidly reversed by dialysis, change in
pH, heat, or the excess addition of another low-molecular
polyhydroxyl ligand (27). Thus, within the intestinal tract,
most ingested boron is probably converted to orthoboric
acid (common name: boric acid), B(OH)3, the normal end
product of hydrolysis of most boron compounds (7). Gastrointestinal
absorption of inorganic boron and subsequent
urinary excretion (33) is near 100%.
Several lines of evidence suggest regulation of boron
in humans. For example, 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 (33). Boron contents in human milks
Weeks After Birth
Mean Concentration and Model
of Boron (ug/kg milk)
B FT Means
B FT Model
B PRT Means
B PRT Model
1 2 3 4 5 6 7 8 9 10 11 12
Figure 8 Model and mean (°æSE) concentrations of boron in breast milk
from mothers of full-term (FT) and premature (PRT) infants; n = 9 per group
over 12 weeks after birth. During the first 12 weeks of lactation, prematurity
affected the rate of change in concentrations (P = 0.01).
were similar and stable throughout lactation of full-term
infants in two cohorts of women living in either Houston,
TX (34), or St. John’s, Newfoundland (Fig. 8) (35), have
been interpreted as suggestive of regulatory mechanisms
for the elements, which remain undefined. Evidence for
the homeostatic control of boron is enhanced further by a
report (36) of a specific borate transporter, NaBC1, in mammalian
cell lines, a finding that has yet to be confirmed by
DIETARY BORON SOURCES AND INTAKES
The tolerable upper intake level (UIL) for boron varies by
life stage (Table 1) (37).No Estimated average requirement,
recommended dietary allowance, or adequate intake has
been established for boron for any age–sex group.
For adults, the amount of boron commonly provided in
a single dietary boron supplement is 0.15 mg (31). However,
the reported amount of boron available per serving
varies considerably among commercially available products
as indicated in the relevant information provided by
Table 1 Upper Limits for Boron Set by the 2001 Food and Nutrition
Board of the National Academy of Sciences (37)
Life stage Age (yr) Upper limit (mg/day)
Children 1–3 3
Adolescents 14–18 17
Adults 19–70 20
Pregnancy ≤18 17
Lactation ≤18 17
various dietary supplement manufacturers. Some manufacturers
publish reported values of 6.0mgboron per serving
of dietary supplement (38). The mean of usual intake
of boron (mg/day) from dietary supplements for children
(1–8 years), adolescents (9–15 years), males (19+ years),
females (19+ years), and pregnant/lactating women is
0.269, 0.160, 0.174, 0.178, and 0.148, respectively. The median
boron intake from supplements in the U.S. population
is approximately 0.135 mg/day (37).
Nonfood Personal Care Products
Boron is a notable contaminant or ingredient of many
nonfood personal care products. For example, an antacid
was reported to have a high concentration of boron
(34.7 g/g) (39) such that the maximum recommended
daily dose would provide 2.0 mg B/day, two times the
estimated daily boron consumption for the overall adult
Dietary Sources and Intakes
Ten representative foods with the highest boron concentrations
are distributed among several food categories
(40): raw avocado (14.3 g/g), creamy peanut butter,
(5.87 g/g); salted dry roasted peanuts (5.83 g/g),
dry roasted pecans (2.64 g/g), bottled prune juice
(5.64 g/g), canned grape juice (3.42 g/g), sweetened
chocolate powder (4.29 g/g), table wine (12.2% alcohol)
(3.64 g/g), prunes with tapioca (3.59 g/g), and granola
with raisins (3.55 g/g). Several fruit, bean, pea, and nut
products contained more than 2 g B/g. Foods derived
from meat, poultry, or fish have relatively low concentrations
Infant foods supply 47% of boron (B) intake to infants.
For toddlers, consumption from fruits and fruit
juices, combined, is twice that from milk/cheese (38% vs.
19%). For adolescents, milk/cheese foods are the single
largest source of boron (18–20%), and for adults and senior
citizens, it is beverages (mainly represented by instant regular
coffee) (21–26%). For all groups (except infants), 7%
to 21% of boron intake is contributed by each of the vegetable,
fruit, and fruit drink products. Infants, toddlers,
adolescent girls and boys, adult women and men, and
senior women and men are estimated to consume the following
amounts of boron: 0.55, 0.54, 0.59, 0.85, 0.70, 0.91,
0.73, and 0.86 mg/day, respectively.
INDICATIONS AND USAGE
Boron and Calcium Metabolism and Bone Structure
There are several lines of evidence that dietary boron is
important for normal bone growth and function. Boron
deprivation induced abnormal limb development in frogs
(41) and retarded maturation of the growth plate in chicks
(42). Dietary boron deprivation decreases bone strength
in pigs (43) and rats (44). The trabecular microarchitecture
of vertebral bone was impaired in rats deprived of the
element (44). Similarly, in mice, modeling and remodeling
of alveolar bone (45), as well as alveolar bone healing
after experimental tooth extraction (46), was impaired by
dietary boron deprivation.
Findings from human studies suggest that boron
influences calcium metabolism. For example, in postmenopausal
women, boron supplementation (3 mg/day)
of a low-boron diet (0.36 mg B/day) resulted in a 5%
increase in urinary calcium excretion (33). A similar
phenomenon occurred in either free-living sedentary or
athletic premenopausal women consuming self-selected
typical Western diets: boron supplementation increased
urinary calcium loss (47). These findings may reflect an
increase in intestinal calcium absorption because increase
in dietary calcium often result in increased urinary calcium
Dietary boron also alleviates the signs of marginal
vitamin D deficiency relevant to bone structure and function.
Marginal vitamin D deficiency impairs bone structure,
elevates plasma alkaline phosphatase concentrations,
and reduces body weight. In the growing rachitic
chick, dietary boron substantially alleviated the perturbed
histomorphometric indices of bone growth cartilage
(42,48), reduced elevated serum concentrations of
alkaline phosphatase (49,50), and improved body weight
Boron and Insulin and Energy Substrate Metabolism
Circulating insulin concentrations respond to dietary
boron in a manner that suggests the element may function
to reduce the amount of insulin needed to maintain
glucose levels. For example, in the rat model (with
overnight fasting), boron deprivation increased plasma
insulin with no concurrent change in glucose concentrations
(52). In the chick model, boron deprivation increased
in situ peak pancreatic insulin release (52). In
older volunteers (men and women) fed a low-magnesium,
marginal copper diet, dietary boron deprivation induced
a modest but significant increase in fasting serum glucose
Findings from several studies indicate that dietary
boron may attenuate the deleterious effects of marginal
vitamin D deficiency on insulin and energy substrate
metabolism. In vitamin D–deprived rats, hyperinsulinemia
was decreased by dietary boron (54). It has been
demonstrated repeatedly in the chick model that physiological
amounts of dietary boron can attenuate the rise
in plasma glucose concentration induced by vitamin D
deficiency (42,48,55). In addition, boron decreases the abnormally
elevated plasma concentrations of pyruvate, ßhydroxybutyrate,
and triglycerides that are typically associated
with this inadequacy (42). It is not understood how
boron deprivation perturbs energy substrate metabolism
in humans and animal models, particularly when other
nutrients are provided in suboptimal amounts.
Boron and Immune Function
Dietary boron may have a role in control of the normal
inflammatory response, especially as it relates to production
of various cytokines. Cytokines, including interferongamma
(IFN-), tumor necrosis factor- (TNF-), and
interleukin-6 (IL-6), are produced and secreted by immune
cells that regulate immune responses. Production of IFN-
and TNF- was increased in peripheral blood monocytes
cultured in the presence of lipopolysaccharide (an inflammatory
agent) after isolation from pigs fed supplemental
dietary boron. In the same animals, boron caused a reduction
in localized inflammation following a challenge with
the antigen phytohemagglutinin (PHA) (56). In cell culture
studies with human fibroblasts (57) and chick embryo cartilage
(58), the addition of boric acid also increased TNF-
release by the respective cells. Certain boron-containing
RG-II s from Panax ginseng leaves enhanced the expression
of IL-6–producing activity of mouse macrophages (59).
Finally, perimenopausal women who excreted <1.0 mg
B/day during the placebo period exhibited an increased
percentage of polymorphonuclear leukocytes during the
boron (as sodium borate) supplementation period (60). Dietary
boron may serve as a signal suppressor that downregulates
specific enzymatic activities typically elevated
during inflammation at the inflammation site. Suppression,
but not elimination, of these enzyme activities by
boron is hypothesized to reduce the incidence and severity
of inflammatory disease.
Boron and Steroid Metabolism
There is a clear evidence that dietary boron affects steroid
metabolism. In particular, circulating concentrations of
vitamin D metabolites are sensitive to boron nutriture.
Findings from animal models indicate that dietary boron
enhances the efficacy of vitamin D but cannot substitute
for the vitamin. In volunteers (men, and women
on or not on estrogen therapy), boron supplementation
after consumption of a low-boron diet increased serum
25-hydroxycholecalciferol concentrations (62.4 °æ 7.5 vs.
44.9 °æ 2.5 mmol/L; mean °æ SEM) (61,62), an effect that
may be especially important during the winter months
when these concentrations normally range between
35 and 105 mmol/L (63).
The circulating concentrations of 17-estradiol also
respond to boron nutriture. Perimenopausal women who
excreted <1.0 mg B/day during the placebo period exhibited
increased serum concentrations of estradiol after
boron supplementation (2.5 mg B/day) of self-selected diets
(60). 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 supplementation
(3 mg B/day) of a low-boron diet (0.25 mg B/2000
kcal) (62). However, plasma estradiol, but not testosterone,
concentrations increased in young male volunteers when
their self-selected diets were supplemented with ample
amounts of boron (10 mg/day) (64).
Boron and Cancer
Indirect evidence from several epidemiological and cell
culture studies indicate that dietary boron intake may affect
cancer risk. For example, observations from epidemiologic
human studies suggest that increased intakes of
boron are associated with decreased risk of prostate (65)
and lung (66) cancers and abnormal cervical cytopathology
(67). In cultures of human prostatic epithelial cells
(not tested for proliferative activity), physiological levels
of boron reduced Ca2+ release from ryanodine receptor sensitive
stores in a dose-dependent manner, without affecting
cytoplasmic Ca2+ concentrations (68). In immunocompromised
mice fed physiological amounts of dietary
boron, the element reduced the growth of transplanted
human prostate adenocarcinoma tumors (69).
As with all other elements, boron produces toxicity in
all tested biological organisms when excessive amounts
are absorbed. The toxicity signs associated with boric acid
when used as an antiseptic in lieu of antibiotics on abraded
epithelium (i.e., surgical wounds and diaper rash) were
overlooked for many years even though signs of poisoning
were reported soon after its introduction into clinical use.
Boron is more bacteriostatic than does bactericidal and,
thus, may suppress bacterial growth.
Deaths can occur at doses between 5 and 20 g of boric
acid for adults and below 5 g total for infants (70,71). Potential
lethal doses are usually cited as 3 to 6 g total for infants
and 15 to 20 g total for adults. However, an independent
examination of 784 cases of boric acid ingestion found
minimal or no toxicity at these intake levels or higher (72).
Signs of acute boron toxicity, regardless of route of administration,
include nausea, vomiting, headache, diarrhea,
erythema, hypothermia, restlessness, weariness, desquamation,
renal injury, and death from circulatory collapse
and shock. Autopsy may reveal congestion and edema of
brain, myocardium, lungs, and other organs, with fatty
infiltration of the liver. Chronic heavy borax dust occupational
exposure (average air concentration: 4.1 mg/m3;
range: 1.2–8.5 mg/m3) may manifest as eye irritation,
nosebleeds, chest tightness, sore throat, dry mouth, and
productive cough (71). 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 electrolytic balance
and supporting kidney function during the worst part of
the illness. Depending upon boron blood levels, treatment
ranges from observation to gastric lavage to dialysis.
Boron is ubiquitous in the environment and daily dietary
boron intakes of adult American males, for example, are
slightly less than 1.0 mg. The evidence to date suggests
that higher animals (43,73) and humans (33,62,74) probably
require boron to support normal biological functions.
Despite the progress made in studies of boron essentiality
for plants, animals, and man, the biochemical mechanisms
responsible for the beneficial physiologic effects of boron
across the phylogenetic spectrum are poorly understood.
However, the unique nature of boron biochemistry suggests
specific lines of investigation. In particular, further
characterization of the various cell signaling molecules
that form complexes with boron under physiological conditions
should provide insights into the specific biochemical
function(s) of boron in humans.
1. Warington K. The changes induced in the anatomical structure
of Vicia Faba by the absence of boron from the nutrient
solution. Ann Bot 1926; 40:27–42.
2. Ahmed I, Yokota A, Fujiwara T. A novel highly boron tolerant
bacterium, Bacillus boroniphilus sp. nov., isolated from
soil, that requires boron for its growth. Extremophiles 2007;
3. Lovatt CJ. Evolution of xylem resulted in a requirement
for boron in the apical meristems of vascular plants. New
Phytol 1985; 99:509–522.
4. Fort DJ. Boron deficiency disables Xenopus laevis oocyte maturation
events. Biol Trace Elem Res 2002; 85:157–169.
5. Rowe RI, Eckhert CD. Boron is required for zebrafish embryogenesis.
J Exp Biol 1999; 202:1649–1654.
6. Carney GE, Bowen NJ. p24 proteins, intracellular trafficking,
and behavior: Drosophila melanogaster provides insights
and opportunities. Biol Cell 2004; 96:271–278.
7. Greenwood NN, Earnshaw A. Chemistry of the Elements.
Oxford, U.K.: Pergamon Press, 1984;155–242.
8. Ralston NVC, Hunt CD. Diadenosine phosphates and Sadenosylmethionine:
Novel boron binding biomolecules
detected by capillary electrophoresis. Biochim Biophys Acta
9. Argust P. Distribution of boron in the environment. Biol
Trace Elem Res 1998; 66:131–143.
10. Butterwick L, de Oude N, Raymond K. Safety assessment
of boron in aquatic and terrestrial environments. Ecotox
Environ Safety 1989; 17:339–371.
11. Woods WG. An introduction to boron: History, sources,
uses, and chemistry. Environ Health Perspect 1994;
12. Barr RD, Clarke WB, Clarke RM, et al. Regulation of lithium
and boron levels in normal human blood: Environmental
and genetic considerations. J Lab Clin Med 1993; 121:614–
13. Weser U. Chemistry and structure of some borate polyol
compounds of biochemical interest. In: Jorgensen C, et al.
eds. Structure and Bonding.Vol. 2. New York,NY: Springer-
14. Greenwood NN. Boron. In: JJ Bailar, et al. eds. Comprehensive
Inorganic Chemistry. Vol. 1. 1st ed. Oxford, U.K.:
Pergamon Press Ltd., 1973:665–990.
15. Spivack AJ, Edmond JM. Boron isotope exchange between
seawater and the oceanic crust. Geochim Cosmochim Acta
16. Van Duin M, Peters JA, Kieboom APG. et al. (Studies on
borate esters I. The pH dependence of the stability of esters
of boric acid and borate in aqueous medium as studied by
11B NMR. Tetrahedron 1984; 40:2901–2911.
17. Sato K, Okazaki T, Maeda K, et al. New antibiotics, aplasmomycins
B and C. J Antibiot (Tokyo) 1978; 31:632–635.
18. Schummer D, Irschik H, Reichenbach H, et al. Antibiotics
from gliding bacteria, LVII. Tartrolons: New
boron-containing macrodiolides from Sorangium cellulosum.
Liebigs Ann Chem 1994; 1994:283–289.
19. Dunitz JD, Hawley DM, Miklos D, et al. Structure of
boromycin. Helv Chim Acta 1971; 54:1709–1713.
20. Chen X, Schauder S, Potier N, et al. Structural identification
of a bacterial quorum-sensing signal containing boron.
Nature 2002; 415:545–549.
21. O’Neill MA, Warrenfeltz D, Kates K, et al.
Rhamnogalacturonan-II, a pectic polysaccharide in
the walls of growing plant cells, forms a dimer that is covalently
cross-linked by a borate ester. J Biol Chem 1996; 271:
22. Kohno J, Kawahata T, Otake T, et al. Boromycin, an anti-HIV
antibiotic. Biosci Biotechnol Biochem 1996; 60:1036–1037.
23. Kim DH, Faull KF, Norris AJ, et al. Borate-nucleotide complex
formation depends on charge and phosphorylation
state. J Mass Spectrom 2004; 39:743–751.
24. McLennan AG. Dinucleoside phosphates—An introduction.
In: McLennan AG, Zamecnik PC, eds. Ap4A and other
dinucleoside polyphosphates. Boca Raton, FL: CRC Press,
25. Kolodny NH, Collins LJ. Proton and phosphorus-31 NMR
study of the dependence of diadenosine tetraphosphate
conformation on metal ions. J Biol Chem 1986; 261:14571–
26. Zubay G. Biochemistry. New York, NY: Macmillan, 1988.
27. Zittle CA. Reaction of borate with substances of biological
interest. In: Nord FF, ed. Advances in Enzymology.
Vol. 12. New York, NY: Interscience Publishers, 1951:493–
28. Albersheim P, An J, Freshour G, et al. Structure and function
studies of plant cell wall polysaccharides. Biochem Soc
Trans 1994; 22:374–378.
29. Wimmer MA, Lochnit G, Bassil E, et al. Membraneassociated,
boron-interacting proteins isolated by boronate
affinity chromatography. Plant Cell Physiol 2009; 50:1292–
30. Hu H, Penn SG, Lebrilla CB, et al. Isolation and characterization
of soluble B-complexes in higher plants. Plant
Physiol 1997; 113:649–655.
31. Physicians’ Desk Reference for Nonprescription Drugs and
Dietary Supplements. 20th ed. Montvale, NJ: Medical Economics
32. Gupta UC, James YW, Campbell CA, et al. Boron toxicity
and deficiency: A review. Can J Soil Sci 1985; 65:381–
33. Hunt CD, Herbel JL, Nielsen FH. Metabolic response of
postmenopausal women to supplemental dietary boron
and aluminum during usual and low magnesium intake:
Boron, calcium, and magnesium absorption and retention
and blood mineral concentrations. Am J Clin Nutr 1997;
34. Hunt CD, Butte NF, Johnson LK. Boron concentrations in
milk from mothers of exclusively breast-fed healthy fullterm
infants are stable during the first four months of lactation.
J Nutr 2005; 135:2383–2386.
35. Hunt CD, Friel JK, Johnson LK. Boron concentrations in
milk from mothers of full-term and premature infants. Am
J Clin Nutr 2004; 80:1327–1333.
36. Park M, Li Q, Shcheynikov N, et al. NaBC1 is a ubiquitous
electrogenic Na(+)-coupled borate transporter essential for
cellular boron homeostasis and cell growth and proliferation.
Mol Cell 2004; 16:331–341.
37. Food and Nutrition Board: Institute of Medicine. Dietary
Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron,
Chromium, Copper, Iodine, Iron, Manganese, Molybdenum,
Nickel, Silicon, Vanadium, and Zinc. Washington,
D.C.: National Academic Press, 2001:773.
38. Swanson Ultra Vitamin D & Boron. Available from: swansonvitamins.
com/SWU212/ItemDetail?n = 0. Accessed
January 20, 2010.
39. Hunt CD, Shuler TR, Mullen LM. Concentration of boron
and other elements in human foods and personal-care products.
J Am Diet Assoc 1991; 91:558–568.
40. Hunt CD, Meacham SL. Aluminum, boron, calcium, copper,
iron, magnesium, manganese, molybdenum, phosphorus,
potassium, sodium, and zinc: Concentrations in common
Western foods and estimated daily intakes by infants, toddlers,
and male and female adolescents, adults, and seniors
in the United States. J Am Diet Assoc 2001; 101:1058–1060.
41. Fort DJ, Stover EL, Rogers RL, et al. Chronic boron or copper
deficiency induces limb teratogenesis in Xenopus. Biol Trace
Elem Res 2000; 77:173–187.
42. Hunt CD, Herbel JL, Idso JP. Dietary boron modifies the
effects of vitamin D3 nutriture on indices of energy substrate
utilization and mineral metabolism in the chick. J
Bone Miner Res 1994; 9:171–181.
43. Armstrong TA, Spears JW, Crenshaw TD, et al. Boron
supplementation of a semipurified diet for weanling pigs
improves feed efficiency and bone strength characteristics
and alters plasma lipid metabolites. J Nutr 2000; 130:2575–
44. Nielsen FH, Stoecker BJ. Boron and fish oil have different
beneficial effects on strength and trabecular microarchitecture
of bone. J Trace Elem Med Biol 2009; 23:195–203.
45. Gorustovich AA, Steimetz T, Nielsen FH, et al. A histomorphometric
study of alveolar bone modelling and remodelling
in mice fed a boron-deficient diet. Arch Oral Biol
46. Gorustovich AA, Steimetz T, Nielsen FH. et al. (Histomorphometric
study of alveolar bone healing in rats fed a borondeficient
diet. Anat Rec (Hoboken) 2008; 291:441–447.
47. Meacham SL, Taper LJ, Volpe SL. Effect of boron supplementation
on blood and urinary calcium, magnesium, and
phosphorus, and urinary boron in athletic and sedentary
women. Am J Clin Nutr 1995; 61:341–345.
48. Hunt CD. Dietary boron modified the effects of magnesium
and molybdenum on mineral metabolism in the
cholecalciferol-deficient chick. Biol Trace Elem Res 1989;
49. Hunt CD, Nielsen FH. Interaction between boron and cholecalciferol
in the chick. In: J Gawthorne, White C, eds. Trace
Element Metabolism in Man and Animals-4. Canberra,
Australia: Australian Academy of Science, 1981:597–600.
50. Kurtoglu V, Kurtoglu F, Coskun B. Effects of boron supplementation
of adequate and inadequate vitamin D3-
containing diet on performance and serum biochemical
characters of broiler chickens. Res Vet Sci 2001; 71:183–187.
51. BaiY, Hunt CD. Dietary boron enhances efficacy of cholecalciferol
in broiler chicks. J Trace Elem Exp Med 1996; 9:117–
52. Bakken NA, Hunt CD. Dietary boron decreases peak pancreatic
in situ insulin release in chicks and plasma insulin
concentrations in rats regardless of vitamin D or magnesium
status. J Nutr 2003; 133:3516–3522.
53. Nielsen FH. Dietary boron affects variables associated with
copper metabolism in humans. In: M Anke, et al., eds. 6th
International Trace Element Symposium 1989. Vol. 4. Jena,
Germany: Karl-Marx-Universitat, Leipzig and Friedrich-
54. Hunt CD, Herbel JL. Boron affects energy metabolism in the
streptozotocin-injected, vitamin D3-deprived rat. Magnes
Trace Elem 1991–1992; 10:374–386.
55. Hunt CD, Herbel JL. Physiological amounts of dietary
boron improve growth and indicators of physiological status
over a 20-fold range in the vitamin D3-deficient chick.
In: M Anke, Meissner D, Mills C, eds. Trace Element
Metabolism in Man and Animals. Vol. 2. Gersdorf, Germany:
Verlag Media Touristik, 1993:714–718.
56. Armstrong TA, Spears JW. Effect of boron supplementation
of pig diets on the production of tumor necrosis factor-and
interferon-. J Anim Sci 2003; 81:2552–2561.
57. Benderdour M, Hess K, Dzondo-Gadet M, et al. Boron
modulates extracellular matrix and TNF alpha synthesis
in human fibroblasts. Biochem Biophys Res Commun 1998;
58. Benderdour M, Hess I, Gadet MD, et al. Effect of boric
acid solution on cartilage metabolism. Biochem Biophys
Res Commun 1997; 234:263–268.
59. Shin K-W, Kiyohara H, Matsumoto T, et al. Rhamnogalacturonan
II from the leaves of Panax ginseng C.A. Meyer as a
macrophage Fc receptor expression-enhancing polysaccharide.
Carbohydr Res 1997; 300:239–249.
60. Nielsen FH, Penland JG. Boron supplementation of perimenopausal
women affects boron metabolism and indices
associated with macromineral metabolism, hormonal status
and immune function. J Trace Elem Exp Med 1999; 12:251–
61. Nielsen FH, Mullen LM, Gallagher SK. Effect of boron depletion
and repletion on blood indicators of calcium status
in humans fed a magnesium-low diet. J Trace Elem Exp
Med 1990; 3:45–54.
62. Nielsen FH, Gallagher SK, Johnson LK, et al. Boron enhances
and mimics some effects of estrogen therapy in postmenopausal
women. J Trace Elem Exp Med 1992; 5:237–246.
63. Tietz NW. Textbook of clinical chemistry. Philadelphia, PA:
W.B. Saunders, 1850.
64. Naghii MR,SammanS. The effect of boron supplementation
on its urinary excretion and selected cardiovascular risk
factors in healthy male subjects. Biol Trace Elem Res 1997;
65. Barranco WT, Hudak PF, Eckhert CD. Evaluation of ecological
and in vitro effects of boron on prostate cancer risk
(United States). Cancer Causes Control 2007; 18:71–77.
66. Mahabir S, Spitz MR, Barrera SL. et al. (Dietary boron and
hormone replacement therapy as risk factors for lung cancer
in women. Am J Epidemiol 2008; 167:1070–1080.
67. Korkmaz M, Uzgoren E, Bakirdere S, et al. Effects of dietary
boron on cervical cytopathology and on micronucleus
frequency in exfoliated buccal cells. Environ Toxicol 2007;
68. Henderson K, Stella SL, Kobylewski S, et al. Receptor activated
Ca(2+) release is inhibited by boric acid in prostate
cancer cells. PLoS One 2009, 4:e6009.
69. Gallardo-Williams MT, Chapin RE, King PE, et al. Boron
supplementation inhibits the growth and local expression of
IGF-1 in human prostate adenocarcinoma (LNCaP) tumors
in nude mice. Toxicol Pathol 2004; 32:73–78.
70. Stokinger HE. The halogens and the nonmetals boron and
silicon. In: GD Clayton, Clayton FE, eds. Patty’s industrial
hygiene and toxicology. New York, NY: JohnWiley & Sons,
71. WHO Task Group on Environmental Health Criteria for
Boron. Boron. Environmental Health Criteria 204: Boron.
Geneva, Switzerland: World Health Organization, 1998;1–
72. Litovitz TL, Klein-Schwartz W, Oderda GM, et al. Clinical
manifestations of toxicity in a series of 784 boric acid ingestions.
Am J Emerg Med 1988; 6:209–213.
73. Hunt CD, Idso JP. Dietary boron as a physiological regulator
of the normal inflammatory response: A review and
current research progress. J Trace Elem Exp Med 1999; 12:
74. Travers RL, Rennie GC, Newnham RE. Boron and arthritis:
The results of a double-blind pilot study. J Nutr Med 1990;
75. Power PP, Woods WG. The chemistry of boron and its speciation
in plants. Plant Soil 1997; 193:1–13.