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Boro

Dietary boron supplementation enhanced the action of estrogen, but not that of parathyroid hormone, to improve trabecular bone quality in ovariectomized rats. Sheng MH, Taper !, "eit H, et al. Biol Trace #lem $es %&&'()%*'&+,'%-. This study investigated whether boron would enhance the ability of 17beta-estradiol (E2) or parathyroid hormone (PT ) to improve bone !uality in ovariectomi"ed #$% rats& 'dult #$% rats were treated for ( w) with vehicle* boron (( ppm as boric acid)* E2 (+, microg-)g-d* sc)* PT (., microg-)g-d* sc)* or a combination of boron and E2 or PT * respectively& The E2 treatment corrected many adverse effects of #$% on bone !uality* increased bone /a* P* and 0g contents* and decreased trabecular plate separation& 1ietary boron supplementation had no effects on these bone parameters in #$% rats& 2hen #$% rats were treated with boron and E2 together* trabecular bone volume (Tb&34-T$) and plate density were increased significantly more than that caused by E2 alone& The boron and E2 combination also increased trabecular bone surface (Tb&3$-T$) and decreased trabecular plate separation in #$% rats& 5n contrast* whereas daily PT in6ection also increased bone /a* 0g* and P contents* Tb&3$-T$* Tb&34-T$* trabecular plate density and thic)ness* and decreased trabecular plate separation in #$% rats* the combination of boron and PT had no additional improvement in bone !uality over that achieved by PT alone& 5n summary* this study shows for the first time that boron enhanced the action of E2* but not that of PT * to improve trabecular bone !uality in #$% rats&

Boron* . $evie/ of its 0utritional 1nteractions and Therapeutic 2ses


3regory S. 4elly, 0.D.
.bstract 3oron is a trace mineral which is found in highest amounts in fruits* vegetables* nuts* and legumes& 'lthough it has not been demonstrated une!uivocally to be an essential nutrient for humans* increasing evidence indicates that boron deficiency and supplementation e7ert measurable biological effects& 3oron has been shown to impact

mineral metabolism* brain function and performance* and selected hormone levels& 3ecause of its impact on mineral metabolism and hormones associated with bone formation* boron supplementation is considered to be important in the prevention of osteoporosis& Epidemiological evidence suggests that ade!uate boron in the diet may also prevent arthritis& 8imited clinical observations support a possible role for boron in the treatment of this condition& ('lt 0ed 9ev 1::7;2(1)<=>-(.) 1ntroduction 3oron is a ubi!uitous constituent of man?s e7ternal environment* which typically occurs in nature as borates hydrated with varying amounts of water& 3oric acid and bora7 are important boron-containing compounds&1 5n trace amounts* boron is essential for the growth of many plants* and is found in animal and human tissues at low concentrations& 1 'lthough it has yet to be recogni"ed as an essential nutrient for humans* recent data from animal and human studies suggest that boron may be important for mineral metabolism* brain function and performance* and prevention of both osteoporosis and osteoarthritis& Sources 3ecause boron in plants is dependent on the availability of boron in the soil* the same food crop can vary greatly in boron content depending on where it is grown& 5n general* soils e7posed to high degrees of precipitation have decreased levels of boron& 2 @ood processing results in additional loss of boron& + @oods of plant origin* such as leafy vegetables* non-citrus fruits* nuts* legumes* and sea vegetables are considered to be the best source of boron&1*= 2ine has also been shown to contribute appreciable amounts of boron to the diet&( ' diet containing an abundance of these items should provide between 2-. mg of boron per day&=* . 1aily inta)e of boron is dependent upon several variables& /oncentration of boron in water varies considerably according to geographic source& 5n some areas* boron in drin)ing water and water-based beverages may account for most of the total dietary boron inta)e& 5ndividual food preference greatly influences daily inta)e of boron& @ruits* vegetables* tubers* and legumes have relatively much higher concentrations of boron than do cereal grains or animal tissues& 3oron has also been determined to be a notable contaminant or ma6or ingredient of many personal-care products and it is occasionally used (boric acid) as a food preservative& 7 5n a recently published study* +2 sub6ects from 4ydney* 'ustralia* ages 2,-(+* were assessed over a 7 day period for their dietary inta)e of boron& The average boron inta)e in male and female sub6ects was found to be 2&2> A-- 1&+ and 2&1. A-- 1&1 mg-day* respectively&( The boron content of selected 'ustralian foods has been found to correlate with values in @innish and B4 @ood and 1rug 'dministration tables and is presented in table 1&

5hemical 6roperties Elemental boron was isolated in 1>,>& 5t is the first member (atomic number () of the metalloid or semiconductor family of elements* which include silicon and germanium* and is the only non-metal of the group 555' elements& 8i)e carbon* boron has a tendency to form double bonds and macromolecules& > 3oron* as boric acid* acts as a 8ewis acid* accepting hydro7yl (# -) ions and leaving an e7cess of protons& : 3ecause boron comple7es with organic compounds containing hydro7yl groups* it is capable of interacting with sugars and polysaccharides* adenosine-(-phosphate* pyrido7ine* riboflavin* dehydroascorbic acid* and pyridine nucleotides& 1, Metabolism 3oron in food* sodium borate and boric acid are well absorbed from the digestive tract& 11 These compounds are also absorbed through damaged s)in and mucous membranes* however* they do not readily penetrate intact s)in& 12 Co accumulation of boron has been observed in soft tissues of animals fed chronic low doses of boron* however* in acute poisoning incidents* the amount of boric acid in brain and liver tissue has been reported to be as high as 2,,, ppm& 2ithin a few days of consumption of high amounts of boron* levels in blood and most soft tissues !uic)ly reach a plateau&1+ Tissue homeostasis is maintained by the rapid elimination of e7cess boron primarily in the urine; with bile* sweat* and breath also contributing as routes of elimination&1, 5n humans* urinary boron e7cretion increases over time in all boronsupplemented sub6ects who have been studied& 1= Evidence suggests that supplemental boron does accumulate in bone* however cessation of e7posure to dietary boron results in a rapid drop in bone boron levels& The half- life of boric acid in animals is estimated to be about one day& 1+ Biological 7unctions 5t has been proposed that boron contributes to living systems by acting indirectly as a proton donor and that it e7erts an influence on cell membrane structure and function& 1( 'lthough the absolute essentiality of boron for plants is well documented* studies to date have not shown it to be une!uivocally essential for either animals or humans& 2ith this in mind* however* boron supplementation has been shown to affect certain aspects of animal physiological function& E7perimental animals supplemented with boron demonstrate a high degree of variability in their response& 5n general* supplemental dietary boron has most mar)ed effects when the diet is deficient in )nown nutrients& 1.

3oron in an animal model has been shown to have an effect upon life span* however* the process is undefined& E7tremes in dietary boron* both deficiency and e7cess levels* decreased the median life span of 1rosophilia by .:D; while supplementing the diet with low levels of boron increased life span by :&(D& 17 3rain electrophysiology and cognitive performance were assessed in response to dietary manipulation of boron (appro7imately ,&2( versus appro7imately +&2( mg boron-2,,, )cal-day) in three studies with healthy older men and women& ' low boron inta)e was shown to result in a decrease in the proportion of power in the alpha band and an increase in the proportion of power in the delta band& #ther changes in left-right symmetry and brain wave coherence were noted in various sites indicating an influence on brain function& 2hen contrasted with the high boron inta)e* low dietary boron resulted in significantly poorer performance (p E ,&,() on tas)s emphasi"ing manual de7terity; eye-hand coordination; attention; perception; encoding and short-term memory; and long-term memory& /ollectively* the data from these studies indicate that boron may play a role in human brain function* alertness and cognitive performance& 1> 3oron supplementation to human sub6ects* who had previously followed a dietary regimen deficient in boron* increased blood hemoglobin concentrations* mean corpuscular hemoglobin* and mean corpuscular hemoglobin concentration; and lowered hematocrit* red cell count* and platelet count& 1: 3oron also impacts mineral metabolism and has been shown to impact levels of certain hormones in human sub6ects& 5n the first nutritional study with humans involving boron* 1+ postmenopausal women first were fed a diet that provided ,&2( mg boron-2,,, )cal for 11: days* and then were fed the same diet with a boron supplement of + mg boron-day for => days& The boron supplementation reduced the total plasma concentration of calcium and the urinary e7cretions of calcium and magnesium* and elevated the serum concentrations of 17 beta-estradiol and testosterone& = 5n a study designed to determine the effects of boron supplementation on blood and urinary minerals in athletic sub6ects on 2estern diets* findings suggested that boron supplementation modestly affected mineral status& 1= Deficiency Signs and Symptoms 5nformation on boron deficiency is very limited* especially in humans& 5t is thought that insufficient inta)e of boron becomes obvious only when the body is stressed in a manner that enhances the need for it& 2hen the diets of animals and humans are manipulated to cause functional deficiencies in nutrients such as* calcium* magnesium* vitamin 1* and methionine* a large number of responses to dietary boron occur& 2, There is evidence that suggests that more than 21 days on a boron deficient diet are re!uired to demonstrate detectable effects in humans&21 The variables that are changed* due to a boron deficient diet* abruptly improve about > days after boron supplementation is introduced& = 2hile by no means being pathognomonic for a boron deficiency* blood urea nitrogen and

creatinine have been found to be elevated during boron depletion* 22 so may be a useful mar)er of a dietary deficiency& 0utrient 1nteractions "itamin D* There is considerable evidence that dietary boron alleviates perturbations in mineral metabolism that are characteristic of vitamin 1+ deficiency& 2+ 'fter 2. days* chic)s fed a diet inade!uate in vitamin 1 e7hibited decreased food consumption and plasma calcium concentrations and increased plasma concentrations of glucose* betahydro7ybutyrate* triglycerides* triiodo-thyronine* cholesterol* and al)aline phosphatase activity& 4upplemental boron returned plasma glucose and triglycerides to concentrations e7hibited by chic)s fed a diet ade!uate in vitamin 1& 2= 5n rachitic chic)s* boron elevated the numbers of osteoclasts 2( and alleviated distortion of the marrow sprouts of the pro7imal tibial epiphysial plate; a distortion characteristic of vitamin 1+ deficiency&2+ igher apparent-balance values of calcium* magnesium* and phosphorus have been observed for rats fed a vitamin 1-deprived diet if the diet is supplemented with boron&1. 5n men over =( and postmenopausal women fed a low magnesium and low copper diet* supplementation with +&2( mg of boron per day increased levels of plasma 12& 2. 5alcium* 3oron supplementation has a favorable impact on calcium metabolism& ' boron supplement of + mg-day mar)edly affected several indices of mineral metabolism of seven women consuming a low-magnesium diet and five women consuming a diet ade!uate in magnesium; the women had consumed a conventional diet supplying about ,&2( mg boron-day for 11: days& 3oron supplementation mar)edly reduced the urinary e7cretion of calcium and magnesium; the depression seemed more mar)ed when dietary magnesium was low&= 5n men over =( and postmenopausal women* changes caused by boron supplementation include; increased concentration of plasma ioni"ed and total calcium* as well as reduced serum calcitonin concentration and urinary e7cretion of calcium& 2. ' 1::+ study demonstrated that a low boron diet elevated urinary calcium e7cretion& 27 5opper* 'vailable evidence indicates that supplemental boron acts to increase serum levels of both copper and copper-dependent en"ymes in humans& 3oron supplementation (+ mg-day)* to five men over the age of =(* four postmenopausal women* and five postmenopausal women on estrogen therapy who had been fed a low boron diet (,&2+ mg-2,,, )cal) for .+ days* resulted in higher erythrocyte supero7ide dismutase* serum en"ymatic ceruloplasmin* and plasma copper& 2> 5n a subse!uent study* these same variables were again found to be higher during boron repletion than while sub6ects were fed a diet low in boron&2>

Magnesium* 2hen magnesium deprivation is severe enough to cause typical signs of deficiency* a significant interaction between boron and magnesium is found& > ' combined deficiency of boron and magnesium causes detrimental changes in the bones of animals* however* supplemental boron elevated plasma 0g concentrations and enhanced growth&2( 3oron supplementation has resulted in increased serum magnesium concentrations in human female sub6ects studied&1+ 5t has been shown that serum magnesium concentrations are greater in sedentary females whose diets are supplemented with boron than in e7ercising female athletes who are supplemented with boron& 2: This finding* while une7plained to date* may indicate an increased loss of boron through urine and perspiration during e7ercise& 6hosphorous* 4upplemental boron seems to lower serum phosphorus concentrations in female sub6ects ages 2,-27;2: however* e7ercise training diminishes these changes* 1+ again possibly indicating increased losses or an increased need for boron as a result of e7ercise& ' low magnesium status along with supplementation of boron may depress the urinary e7cretion of phosphorus& This does not occur in women with an ade!uate magnesium inta)e&= Methionine 8 .rginine* 5n e7perimental animals* a beneficial impact is consistently observed after boron supplementation when the diet contains marginal methionine and lu7uriant arginine& 'mong the signs e7hibited by rats fed a diet marginal in methionine and magnesium are depressed growth and bone magnesium concentration* and elevated spleen weight-body weight and )idney weight-body weight ratios& @indings indicate that the severity of these symptoms is alleviated with boron supplementation& +, Hormone 1nteractions 5n rats* supplemental dietary boron substantially depressed plasma insulin* plasma pyruvate concentrations* and creatine )inase activity and increased plasma thyro7ine (T=) concentrations& 3oron supplementation also decreased plasma aspartate transaminase activity&+1 5n animal e7periments* boron supplementation offsets the elevation in plasma al)aline phosphatase caused by vitamin 1 deficiency& 22 Cielsen hypothesi"ed that boron might be re!uired for the synthesis of steroid hormones as well as vitamin 1& 3ecause the biosynthesis of steroid hormones such as vitamin 1* testosterone* and 17 beta-estradiol involves one or more hydro7ylations and because of boron?s ability as a lewis acid to comple7 with hydro7yl groups* he suggested that boron may facilitate the addition of hydro7yl groups to the steroid structures& = 5t has also been suggested that boron may act in an unspecified manner to protect hormones from rapid inactivation&= 'n increase in dietary inta)e of boron from ,&2( to +&2( mg-d has been reported to increase plasma 17 beta-estradiol by more than (,D and to more than double plasma

testosterone levels in postmenopausal women& The elevation seemed more mar)ed when dietary magnesium was low&= 5n a subse!uent study of healthy men* boron supplementation resulted in an increase in the concentrations of both plasma estrogen and testosterone; however* other published trials do not support these observations& ( Ten male bodybuilders age 2,-2. were given a 2&(-mg boron supplement* while nine male bodybuilders age 21-27 were given a placebo for 7 wee)s& 3ecause both groups demonstrated significant increases in total testosterone (p E ,&,1)* lean body mass (p E ,&,1)* and one repetition ma7imum s!uat (p E ,&,,1) and bench press (p E ,&,1)* the authors concluded that the gains were a result of 7 wee)s of bodybuilding* not of boron supplementation&+2 Table 2 lists boron?s impact on selected hormones in either animals and humans& 4ome of these interactions have only been demonstrated in animal models (F) while others have not been demonstrated une!uivocally to date in all age and gender segments of a human population (FF)& 5linical .pplications of Boron 9steoporosis* There is considerable evidence that both compositional and functional properties of bone are affected by boron status& ++ 5n e7perimental animals* histologic findings suggest that supplemental boron enhances maturation of the growth plate& 2= 3oron is also found at the highest concentrations in growing and calcifying areas of long bones&= 5n two human studies* =* 22 boron deprivation caused changes in indices associated with calcium metabolism in a manner that could be construed as being detrimental to bone formation and maintenance; these changes were enhanced by a diet low in magnesium& The author concluded that boron and magnesium are apparently needed for optimal calcium metabolism and are thus needed to prevent the e7cessive bone loss which often occurs in postmenopausal women and older men& 22 .rthritis* 5t has been suggested that boron deficiency in food may be a contributing factor in some cases of arthritis&+= 5n areas of the world where boron inta)e routinely is 1&, mg or less per day* the estimated incidence of arthritis ranges from 2, to 7,D* whereas in areas of the world where boron inta)e ranges from + to 1, mg per day* the estimated incidence of arthritis ranges from , to 1,D& += 'nalytical evidence indicates that persons with arthritis have lower boron concentrations in femur heads* bones* and synovial fluid when compared with persons without this disorder& There have also been observations that bones of patients using boron supplements are much harder to cut than those of patients not supplementing with boron&+ 5n 1:.1* the first anecdotal evidence suggesting that boron may be beneficial for osteoarthritis was presented when one patient had reduction of swelling and stiffness and remained symptom free for 1 year following supplementation of + mg of elemental

boron twice daily for + wee)s& ' human study also offers evidence that boron supplementation may be beneficial in the treatment of this condition& 5n a double-blind placebo-controlled trial of 2, sub6ects with osteoarthritis* (,D of sub6ects receiving a daily supplement containing . mg of boron noted sub6ective improvement in their condition& #nly 1,D of those receiving a placebo improved during the same time interval& There was greater improvement in the condition of all 6oints (pE,&,1) as well as less pain on movement (pE,&,,1) in sub6ects receiving the boron supplementation& +( /linical observations indicate that children with 6uvenile arthritis (4till?s disease) improve with boron supplementation (.-: mg per day) in 2-+ wee)s* while adults with osteoarthritis may re!uire between 2-= months of supplementation before benefits are detected& Persons with rheumatoid arthritis may e7perience an aggravation of symptoms ( er7heimer response) for 1 to + wee)s* but generally notice improvement within = wee)s of beginning boron supplementation&+ To:icology 'lthough boron is potentially to7ic to all organisms* and* as boric acid and bora7* has been used as a pesticide and food preservative* higher animals usually do not accumulate boron because of their ability to rapidly e7crete it& : 'uthenticated cases of poisoning in humans have been few and have primarily been the result of accidental ingestion of insecticides and household products containing borates* or use of large amounts of boric acid in the treatment of burns&+. The improper use of boric acid- containing antiseptics is still one of the most common causes of to7ic accidents in newborns and infants& 4ince boric acid is readily absorbed through damaged s)in* it should not be applied topically to e7tensive wounds& 11 5n animals* chronic low-level boron e7posure has been shown to cause reduced growth* cutaneous disorders and suppression of male reproductive system function& +7 4tudies indicate that male rodents suffer testicular atrophy with dietary e7posure to boric acid above =(,, ppm and have decreased sperm motility at all e7posure levels above 1,,, ppm&+> Goats orally dosed with to7ic but sublethal amounts of boron show significant increases in pac)ed cell volume* hemoglobin* inorganic phosphate* creatine phospho)inase* con6ugated bilirubin* sodium* glucose* cholesterol* and aspartate transaminase& The following serum components were significantly decreased after boron dosing< al)aline phosphatase* magnesium* glutamyltransferase and potassium& There was also an elevation of cerebrospinal fluid monoamine metabolites& +: umans given 1,, mg of boron intravenously =, or 27, mg of boric acid orally reported no discomfort and showed no obvious signs of to7icity& =1 'irborne e7posures to boron o7ide and its hydration product* boric acid* have been reported to cause respiratory and eye irritation&=2

/ommon indications of acute boron to7icity include nausea* and vomiting and diarrhea which are blue-green in color&=+ #ther symptoms seen with acute e7posure are abdominal pain* an erythemetous rash involving both the s)in and mucous membranes* stimulation or depression of the central nervous system* convulsions* hyperpyre7ia* renal tubular damage* abnormal liver function and 6aundice& 11 5ncreased urinary riboflavin e7cretion has also been reported subse!uent to acute boric acid ingestion& == 4ymptoms of chronic into7ication include anore7ia* gastro-intestinal disturbances* debility* confusion* dermatitis* menstrual disorders* anemia* convulsions and alopecia& 11 3ecause of its ability to increase the e7cretion of boron* in cases of to7icity* Cacetylcysteine is the preferred intervention& =( Dosage The optimal dose of boron for prevention of osteoporosis and proper physiological function appears to be between +-. mg-day& 2hile it is best to obtain boron by means of a diet with an abundance of fruits* vegetables* legumes* and nuts; persons whose diet is limited in these items should consider ta)ing a supplement containing + mg of elemental boron& 5n persons with arthritis* a trial period of 2-= months with a dose of + mg of boron three times daily seems to be indicated& Summary 'lthough degrees of s)eletal response to boron are modified by other nutritional variables that include calcium* magnesium* vitamin 1* methionine and arginine* there is considerable evidence that both compositional and functional properties of bone are affected by boron status& @indings suggest that boron is an important nutrient not only for mineral metabolism but for varied aspects of optimal health in humans& 2hile all published trials are not in agreement on the impact of boron supplementation on levels of se7 hormones* it seems evident that boron raises levels in postmenopausal women and may have a potential impact in other segments of the population& 3ased on available information* boron appears to offer benefits in the prevention of osteoporosis and arthritis& 5t is also a safe and potentially-effective addition that should be considered as an option in any treatment regimen for arthritis& $eferences 1& Caghii 09* 4amman 4& The role of boron in nutrition and metabolism& Prog @ood Cutr 4ci 1::+;17<++1-+=:&

2& oung H- & The physiology of boron and molybdenum in plants& 5n< #)a6ima * Britani 5* and oung -H& The significance of minor elements on plant physiology& '4P'/ Taiwan* 1:7(<.1-..& +& Cewnham 9E& The role of boron in human nutrition& I 'ppl Cutr 1::=;=.<>1->(& =& Cielsen @ * unt /1* 0ullen 80* et al& Effect of dietary boron on mineral* estrogen* and testosterone metabolism in postmenopausal women& @'4E3 I 1:>7;1<+:=-+:7& (& Caghii 09* 8yons P0* 4amman 4& The boron content of selected foods and the estimation of its daily inta)e among free-living sub6ects& I 'mer /ol Cutr 1::.;1(<.1=.1:& .& 0c3ride I& 3anishing brittle bones with boronJ 'gric 9es 1:>7;Cov-1ec<12-1+& 7& unt /1* 4huler T9* 0ullen 80& /oncentration of boron and other elements in human foods and personal-care products& I 'm 1iet 'ssoc 1::1;:1< ((>-(.>& >& Cielsen @ & 3oron - an overloo)ed element of potential nutritional importance& Cutr Today 1:>>;2+<=-7& :& 8oomis 21* 1urst 92& /hemistry and biology of boron& 3io@actors 1::2;+<22:-2+:& 1,& Kittle /'& 9eaction of borate with substances of biological interest& 'dv En"ymol 1:(1;12<=:+-(27& 11& Cielsen @ & Bltratrace minerals< 3oron& 5n< 4hils 0E* Loung $9& 0odern Cutrition in ealth and 1isease& 8ea M @ebiger* Philadelphia* 1:>><2>1-2>+& 12& 9eynolds IE@* ed& 0artindale-The E7tra Pharmacopoeia& 8ondon;1::.<1.>,& 1+& 0oseman 9@& /hemical disposition of boron in animals and humans& Environ ealth Perspect 1::=;1,2 4uppl 7<11+-117 1=& 0eacham 48* Taper 8I* $olpe 48& Effect of boron supplementation on blood and urinary calcium* magnesium* and phosphorus* and urinary boron in athletic and sedentary women& 'm I /lin Cutr 1::(;.1<+=1-+=(& 1(& 3arr 91* 3arton 4'* 4chull 2I& 3oron levels in man< preliminary evidence of genetic regulation and some implications for human biology& 0ed ypotheses 1::.;=.<2>.-2>:& 1.& 1upre IC* Heenan 0I* egsted 0* et al& Effects of dietary boron in rats fed a vitamin 1-deficient diet& Environ ealth Perspect 1::=;1,2 4uppl 7<((-(>&

17& 0assie 9* 2hitney 4I* 'iello $9* et al& /hanges in boron concentration during development and ageing of 1rosophila and effect of dietary boron on life span& 0ech 'geing 1ev 1::,;(+<1-7 1>& Penland IG& 1ietary boron* brain function* and cognitive performance& Environ ealth Perspect 1::=;1,2 4uppl 7<.(-72& 1:& Cielsen @ * 0ullen 80* Cielsen EI& 1ietary boron affects blood cell counts and hemoglobin concentrations in humans& I Trace Elem E7p 0ed 1::1;=<211-22+& 2,& Cielsen @ & Cew essential trace elements for the life sciences& 3iol Trace Elem 9es 1::,;2.-27<(::-.11& 21& Cielsen @ & @acts and fallacies about boron& Cutr Today 1::2;0ay-Iune<.-12& 22& Cielsen @ & 4tudies on the relationship between boron and magnesium which possibly affects the formation and maintenance of bones& 0ag Trace Elem 1::,;:<.1-.:& 2+& unt /1& The biochemical effects of physiologic amounts of dietary boron in animal nutrition models& Environ ealth Perspect 1::=;1,2 4uppl 7<+(-=+& 2=& unt /1* erbel I8* 5dso IP& 1ietary boron modifies the effects of vitamin 1+ nutrition on indices of energy substrate utili"ation and mineral metabolism in the chic)& I 3one 0iner 9es 1::=;:<171-1>2& 2(& unt /1& 1ietary boron modified the effects of magnesium and molybdenum on mineral metabolism in the cholecalciferol-deficient chic)& 3iol Trace Elem 9es 1:>:;22<2,1-22,& 2.& Cielsen @ * 4huler T9* Gallagher 4H& Effects of boron depletion and repletion on blood indicators of calcium status in humans fed a magnesium-low diet& I Trace Elem E7p 0ed 1::,;+<=(-(=& 27& 3eattie I * Peace 4& The influence of a low-boron diet and boron supplementation on bone* ma6or mineral and se7 steroid metabolism in postmenopausal women& 3r I Cutr 1::+;.:<>71->>=& 2>& Cielsen @ & 3iochemical and physiologic conse!uences of boron deprivation in humans& Environ ealth Perspect 1::=;1,2 4uppl 7<(:-.+& 2:& 0eacham 48* Taper 8I* $olpe 48& Effects of boron supplementation on bone mineral density and dietary* blood* and urinary calcium* phosphorus* magnesium* and boron in female athletes& Environ ealth Perspect 1::=;1,2 4uppl 7<7:->2& +,& Cielsen @ * 4huler T9* Kimmerman TI* et al& 0agnesium and methionine deprivation affect the response of rats to boron deprivation& 3iol Trace Elem 9es 1:>>;17<:1-1,7&

+1& unt /1* erbel I8& 3oron affects energy metabolism in the strepto"otocin-in6ected* vitamin 1+-deprived rat& 0agnes Trace Elem 1::1-:2;1,<+7=-+>.& +2& @errando ''* Green C9& The effect of boron supplementation on lean body mass* plasma testosterone levels* and strength in male bodybuilders& 5nt I 4port Cutr 1::+;+<1=,-1=:& ++& 0c/oy * Henney 0'* 0ontgomery /* et al& 9elation of boron to the composition and mechanical properties of bone& Environ ealth Perspect 1::=;1,2 4uppl 7<=:-(+& +=& Cewnham 9E& 'gricultural practices affect arthritis& Cutr ealth 1::1;7<>:-1,,& +(& Travers 98* 9ennie G/* Cewnham 9E& 3oron and arthritis< the result of a doubleblind pilot study& I Cutr 0ed 1::,;1<127-1+2& +.& 8ocatelli /* 0inoia /* Tonini 0* et al& uman to7icology of boron with special reference to boric acid poisoning& G 5tal 0ed 8av 1:>7;:<1=1-1=.& +7& 0inoia /* Gregotti /* 1i Cucci '* et al& To7icology and health impact of environmental e7posure to boron& ' review& G 5tal 0ed 8av 1:>7;:<11:-12=& +>& /hapin 9E* Hu 22& The reproductive to7icity of boric acid& Environ ealth Perspect 1::=;1,2 4uppl 7<>7-:1& +:& 4is) 13* /olvin 30* 0errill '* et al& E7perimental acute inorganic boron to7icosis in the goat< effects on serum chemistry and /4@ biogenic amines& $et um To7icol 1::,;+2<2,(-211& =,& Iansen I'* 'nderson I* 4chou I4& 3oric acid single dose pharmo)inetics after intravenous administration to man& 'rch To7icol 1:>=;((<.=-.7& =1& 'as Iansen I* 4chou I4* 'ggerbec) 3& Gastro-intestinal absorption and in vitro release of boric acid from water-emulsifying agents& @d /hen To7ic 1:>=;22<=:-(+& =2& Garabrant 1 * 3ernstein 8* Peters I0* et al& 9espiratory and eye irritation from boron o7ide and boric acid dusts& I #ccup 0ed 1:>=;2.<(>=-(>.& =+& $on 3urg 9& 3oron* boric acid* and boron o7ide& 8 'ppl To7icol 1::2;12<1=:-1(2& ==& Pinto I* uang LP* 0c/onell 9I* et al& 5ncreased urinary riboflavin e7cretion resulting from boric acid ingestion& I 8ab /lin 0ed 1:7>;:2<12.-1+=& =(& 3anner 2 Ir* Hoch 0* /apin 10* et al& E7perimental chelation therapy in chromium* lead* and boron into7ication with C-acetylcysteine and other compounds& To7icol 'ppl Pharmacol 1:>.;>+<1=2-1=7&