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Relation of boron to the composition and mechanical properties of bone.

A review of the experimental studies relating boron to biological effects on appendicular and axial bones in animal models suggests that numerous influences, known and unknown, affect the responsiveness of bone to dietary boron. Degrees of skeletal response to boron are modified by other nutritional variables that include calcium, magnesium, vitamin D, and fluoride. Evidence suggests that appendicular and axial bones may differ in their responses. Tests of the mechanical properties of bones may provide useful criteria for assessing the impacts of boron status on bone. These tests might resolve questions about optimal intakes of boron because mechanical properties sometimes respond to boron when composition of bones does not. Difficulty in interpreting some of the existing research arises because of the incipient state of knowledge regarding boron nutriture, to analytical problems associated with determining accurately the small quantities of boron in feed and tissues, and to technological difficulties in controlling extraneous exposure of experimental animals to boron. Yet there is considerable evidence that both compositional and functional properties of bone are affected by boron status.

Animals↗

Biochemical and physiologic consequences of boron deprivation in humans.

Boron deprivation experiments with humans have yielded some persuasive findings for the hypothesis that boron is an essential nutrient. In the first nutritional study with humans involving boron, 12 postmenopausal women first were fed a diet that provided 0.25 mg boron/2000 kcal for 119 days, and then were fed the same diet with a boron supplement of 3 mg boron/day for 48 days. The boron supplementation reduced the total plasma concentration of calcium and the urinary excretions of calcium and magnesium, and elevated the serum concentrations of 17 beta-estradiol and testosterone. This study was followed by one in which five men over the age of 45, four postmenopausal women, and five postmenopausal women on estrogen therapy were fed a boron-low diet (0.23 mg/2000 kcal) for 63 days, then fed the same diet supplemented with 3 mg boron/day for 49 days. The diet was low in magnesium (115 mg/2000 kcal) and marginally adequate in copper (1.6 mg/2000 kcal) throughout the study. This experiment found higher erythrocyte superoxide dismutase, serum enzymatic ceruloplasmin, and plasma copper during boron repletion than boron depletion. The design of the most recent experiment was the same as the second study, except this time the diet was adequate in magnesium and copper. Estrogen therapy increased plasma copper and serum 17 beta-estradiol concentrations; the increases were depressed by boron deprivation. Estrogen ingestion also increased serum immunoreactive ceruloplasmin and erythrocyte superoxide dismutase; these variables also were higher during boron repletion than depletion for all subjects, not just those ingesting estrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density↗

Essentiality of boron for healthy bones and joints.

Since 1963, evidence has accumulated that suggests boron is a safe and effective treatment for some forms of arthritis. The initial evidence was that boron supplementation alleviated arthritic pain and discomfort of the author. This was followed by findings from numerous other observations epidemiologic and controlled animal and human experiments. These findings included a) analytical evidence of lower boron concentrations in femur heads, bones, and synovial fluid from people with arthritis than from those without this disorder; b) observation evidence that bones of patients using boron supplements are much harder to cut than those of patients not using supplements; c) epidemiologic evidence that in areas of the world where boron intakes usually are 1.0 mg or less/day the estimated incidence of arthritis ranges from 20 to 70%, whereas in areas of the world where boron intakes are usually 3 to 10 mg, the estimated incidence of arthritis ranges from 0 to 10%; d) experimental evidence that rats with induced arthritis benefit from orally or intraperitoneally administered boron; e) experimental evidence from a double-blind placebo-boron supplementation trial with 20 subjects with osteoarthritis. A significant favorable response to a 6 mg boron/day supplement was obtained; 50% of subjects receiving the supplement improved compared to only 10% receiving the placebo. The preceding data indicate that boron is an essential nutrient for healthy bones and joints, and that further research into the use of boron for the treatment or prevention of arthritis is warranted.

Aged↗

Effects of dietary boron supplementation on broilers.

Two experiments were conducted with a total of 432 broiler chicks to investigate the influence of supplementing different amounts of boron to practical corn-soybean meal diets. The birds were housed in batteries and had free access to feed and water. In Experiment 1, 144 1-day-old broiler chicks were fed a basal diet supplemented with 0, 5, 40, 80, or 120 ppm boron for 21 days. Female body weight was not influenced by the dietary treatments. However, males supplemented with 5 ppm boron were heavier and their tibias resisted more load than the control birds. Overall feed conversion was not influenced by boron. In Experiment 2, 288 1-day-old broiler chicks were fed a basal diet supplemented with 0, 60, 120, 240, or 300 ppm boron for 22 days. Male and female body weights of the 300-ppm group were lower than those of the control birds. Percentage tibia ash was highest with 300 ppm boron. No significant differences were found in intestinal tract weight (grams of intestine per 100 g body weight) among treatments. Boron concentration in the breast muscle and liver increased as dietary concentration of boron increased. Data collected in these two experiments indicated that consumption of diets containing up to 240 ppm boron from hatch to 21 days of age was not detrimental to broiler performance. Data were not conclusive on the need for supplemental boron in broiler diets based on corn and soybean meal.

Animals↗

Toxicity of boron to rainbow trout: a weight-of-the-evidence assessment.

From the large data set available on the toxicity of boron to aquatic organisms, the toxicity of boron to the early life stages of rainbow trout (Oncorhyncus mykiss) is the seminal issue relative to setting water quality criteria and effluent standards. Issues associated with the early life stage studies are the flat concentration-response curve, the low threshold of toxicity, and teratogenic effects observed. Recent laboratory and field studies offer new experimental data that make a weight-of-the-evidence assessment timely. In a re-examination of the effect of boron on the embryo-larval stage in rainbow trout and zebrafish, adverse effects due to boron deficiency are observed which decrease with increasing dose. It was found that low concentrations of boron stimulate embryonic growth in rainbow trout and increase the viability and survival of embryonic zebrafish. As boron concentration is further increased, the dose-response curve becomes flat as homeostatic processes are active; this is followed at higher doses by a new adverse response that increases with increasing dose. As a result, the dose-response relationship is U shaped, consistent with the characteristic shape of an essential micronutrient. Thus, effects originally reported to be toxicity at low exposures rather may be due to boron deficiency. Water analyses in trout hatcheries and field studies in wild trout streams add additional information on the toxicity of boron to trout. Of particular note is a controlled field study carried out in the Firehole River in Yellowstone Park (WY, USA), where trout populations survive and reproduction successfully occurs in natural water containing boron concentrations up to and in some cases greater than 1.0 mg B/L. Teratogenic effects due to boron exposure were not observed in any of these more recent studies.

Animals↗

The role of boron in nutrition and metabolism.

A large number of responses to dietary boron occur when the boron content of the diet is manipulated. Numerous studies suggest that boron interacts with other nutrients and plays a regulatory role in the metabolism of minerals, such as calcium, and subsequently bone metabolism. Although the mechanism of action has not been defined, it may be mediated by increasing the concentration of steroid hormones such as testosterone and beta-oestradiol. Boron is obtained from a diet rich in fruits, vegetables, nuts and legumes. The daily intake has been estimated to range from 0.3-41 mg per day. The wide range is due to the variation of the analytical methods used and differences in the soil content of boron. Based on a limited number of studies, increasing dietary boron results in increases in the boron concentration of all tissues. Large amounts of boron are well tolerated while consistent signs of deficiency include depressed growth and a reduction in some blood indices, particularly steroid hormone concentrations. Via its effect on steroid hormones and interaction with mineral metabolism, boron may be involved in a number of clinical conditions such as arthritis. Further research is required before boron is accepted as an essential nutrient for humans.

Animals↗

Toxicity, biodistribution, and convection-enhanced delivery of the boronated porphyrin BOPP in the 9L intracerebral rat glioma model.

PURPOSE: To investigate the toxicity, biodistribution, and convection-enhanced delivery (CED) of a boronated porphyrin (BOPP) that was designed for boron neutron capture therapy and photodynamic therapy. METHODS AND MATERIALS: For the toxicity study, Fischer 344 rats were injected with graded concentrations of BOPP (35-100 mg/kg) into the tail vein. For boron biodistribution studies, 9L tumor-bearing rats received BOPP either systematically (intravenously) or locally. RESULTS: All rats that received 70 mg/kg BOPP and 70% of rats that received < or = 60 mg/kg BOPP i.v. either had to be euthanized or died within 4 days of injection. In the biodistribution study, boron levels were relatively high in liver, kidney, spleen, and adrenal gland tissue, and moderate levels were found in all other organs. The maximum tumor boron concentration was 21.4 mug/g at 48 h after i.v. injection; this concentration of boron in brain tumors is at the low end of the range considered optimal for therapy. In addition, the tumor/blood ratio (approximately 1.2) was not optimal. When BOPP was delivered directly into intracerebral 9L tumors with CED, we obtained tumor boron concentrations much greater than those obtained by i.v. injection. Convection-enhanced delivery of 1.5 mg BOPP produced an average tumor boron level of 519 mug/g and a tumor/blood ratio of approximately 1850:1. CONCLUSIONS: Our study demonstrates that changing the method of BOPP delivery from i.v. to CED significantly enhances the boron concentration in tumors and produces very favorable tumor/brain and tumor/blood ratios.

Animals↗

Synthesis and in vivo murine evaluation of Na4[1-(1'-B10H9)-6-SHB10H8] as a potential agent for boron neutron capture therapy.

Reaction of the normal isomer of [B20H18]2- and the protected thiol anion, [SC(O)OC(CH3)3]-, produces an unexpected isomer of [B20H17SC(O)OC(CH3)3]4- directly and in good yield. The isomer produced under mild conditions is characterized by an apical-apical boron atom intercage connection as well as the location of the thiol substituent on an equatorial belt adjacent to the terminal boron apex. Although the formation of this isomer from nucleophilic attack of the normal isomer of [B20H18]2- has not been reported previously, the isomeric assignment has been unambiguously confirmed by one-dimensional and two-dimensional 11B NMR spectroscopy. Deprotection of the thiol substituent under acidic conditions produces a protonated intermediate, [B20H18SH]3-, which can be deprotonated with a suitable base to yield the desired product, [B20H17SH]4-. The sodium salt of the resulting [B20H17SH]4- ion has been encapsulated in small, unilamellar liposomes, which are capable of delivering their contents selectively to tumors in vivo, and investigated as a potential agent for boron neutron capture therapy. The biodistribution of boron was determined after intravenous injection of the liposomal suspension into BALB/c mice bearing EMT6 mammary adenocarcinoma. At low injected doses, the tumor boron concentration increased throughout the time-course experiment, resulting in a maximum observed boron concentration of 46.7 micrograms of B per g of tumor at 48 h and a tumor to blood boron ratio of 7.7. The boron concentration obtained in the tumor corresponds to 22.2% injected dose (i.d.) per g of tissue, a value analogous to the most promising polyhedral borane anions investigated for liposomal delivery and subsequent application in boron neutron capture therapy.

Adenocarcinoma↗

Spectromicroscopy of boron in human glioblastomas following administration of Na2B12H11SH.

Boron neutron capture therapy (BNCT) is an experimental, binary treatment for brain cancer which requires as the first step that tumor tissue is targeted with a boron-10 containing compound. Subsequent exposure to a thermal neutron flux results in destructive, short range nuclear reaction within 10 microm of the boron compound. The success of the therapy requires than the BNCT agents be well localized in tumor, rather than healthy tissue. The MEPHISTO spectromicroscope, which performs microchemical analysis by x-ray absorption near edge structure (XANES) spectroscopy from microscopic areas, has been used to study the distribution of trace quantities of boron in human brain cancer tissues surgically removed from patients first administered with the compound Na2B12H11SH (BSH). The interpretation of XANES spectra is complicated by interference from physiologically present sulfur and phosphorus, which contribute structure in the same energy range as boron. We addressed this problem with the present extensive set of spectra from S, B, and P in relevant compounds. We demonstrate that a linear combination of sulfate, phosphate and BSH XANES can be used to reproduce the spectra acquired on boron-treated human brain tumor tissues. We analyzed human glioblastoma tissue from two patients administered and one not administered with BSH. As well as weak signals attributed to BSH, x-ray absorption spectra acquired from tissue samples detected boron in a reduced chemical state with respect to boron in BSH. This chemical state was characterized by a sharp absorption peak at 188.3 eV. Complementary studies on BSH reference samples were not able to reproduce this chemical state of boron, indicating that it is not an artifact produced during sample preparation or x-ray exposure. These data demonstrate that the chemical state of BSH may be altered by in vivo metabolism.

Borohydrides↗

Biodistribution of boronophenylalanine in patients with glioblastoma multiforme: boron concentration correlates with tumor cellularity.

Boron-10 (10B) concentrations were measured in 107 surgical samples from 15 patients with glioblastoma multiforme who were infused with 95 atom% 10B-enriched p-boronophenylalanine (BPA) intravenously for 2 h just prior to surgery at doses ranging from 98 to 290 mg BPA/kg body weight. The blood 10B concentration reached a maximum at the end of the infusion (ranging from 9.3 to 26.0 microg 10B/g) and was proportional to the amount of BPA infused. The boron concentrations in excised tumor samples ranged from 2.7 to 41.3 microg 10B/g over the range of administered BPA doses and varied considerably among multiple samples from individual patients and among patients at the same BPA dose. A morphometric index of the density of viable-appearing tumor cells in histological sections obtained from samples adjacent to, and macroscopically similar to, the tumor samples used for boron analysis correlated linearly with the boron concentrations. From that correlation it is estimated that 10B concentrations in glioblastoma tumor cells were over four times greater than concurrent blood 10B concentrations. Thus, in the dose range of 98 to 290 mg BPA/kg, the accumulation of boron in tumor cells is a linear function of BPA dose and the variations observed in boron concentrations of tumor specimens obtained surgically are largely due to differences in the proportion of nontumor tissue (i.e. necrotic tissue, normal brain) present in the samples submitted for boron analysis. The tumor:blood 10B concentration ratio derived from this analysis provides a rationale for estimating the fraction of the radiation dose to viable tumor cells resulting from the boron neutron capture reaction based on measured boron concentrations in the blood at the time of BNCT without the need for analysis of tumor samples from individual patients.

Boron↗

Root Growth Inhibition in Boron-Deficient or Aluminum-Stressed Squash May Be a Result of Impaired Ascorbate Metabolism.

Although cessation of growth is the most apparent symptom of boron deficiency, the biochemical function of boron in growth processes is not well understood. We propose that the action of boron in root meristems is associated with ascorbate metabolism. Total inhibition of root growth in squash (Cucurbita pepo L.) plants transferred to boron-free medium coincided with a major decrease (up to 98%) in the ascorbate concentration of root apices. Under low-boron conditions, in which root growth was partially inhibited, ascorbate concentration declined in proportion to growth rate. The decline in ascorbate concentration in boron-deficient root tips was not related to ascorbate oxidation. Ascorbate added to the medium improved root growth in plants supplied with insufficient boron. Increasing concentrations of aluminum in the nutrient medium caused progressive inhibition of root growth and a parallel reduction in ascorbate concentration of root apices. Elevated boron levels improved root growth under toxic aluminum conditions and produced root apices with higher ascorbate concentrations. To our knowledge, this is the first report of a correlation between boron nutrition, ascorbate concentration in root apices, and growth. These findings show that root growth inhibition resulting from either boron deficiency or aluminum toxicity may be a consequence of disrupted ascorbate metabolism.

Journal Article↗

Autoradiographic Examination of Meristems of Intact Boron-deficient Squash Roots Treated with Tritiated Thymidine.

Intact roots of boron-sufficient squash (Cucurbita pepo L.) plants, plants entering boron deficiency, and plants recovering from boron deficiency were exposed to tritiated thymidine at the end of the treatment period to label the replicating DNA of root tip cells. Using histological sections, autoradiographs of intact root meristems were prepared. The labeling pattern in +B root tips revealed the presence of a well defined quiescent center. The ability of root tip cells to incorporate label is correlated with the total root elongation during the -B treatment period. A greater amount of total root elongation during boron deficiency and recovery reflects the fact that root tip cells have retained their ability to synthesize DNA and enter mitosis for a longer time. In roots recovering from boron deficiency, cells of the quiescent center were seen to play no part in the recovery process in roots treated for as long as 20 hours in a -B nutrient solution. They were inactive before, during, and after the -B treatment. Cessation of mitosis occurs as early as 6.5 hours after boron is withheld from the nutrient solution while DNA synthesis can occur for as long as 20 hours after withholding boron. It was concluded that boron is essential for continued DNA synthesis and mitotic activity. The absence of boron results in the cessation of mitosis and DNA synthesis within 20 hours from the time boron is withheld.

Journal Article↗

A new boronated porphyrin (STA-BX909) for neutron capture therapy: an in vitro survival assay and in vivo tissue uptake study.

A new boronated porphyrin compound (STA-BX909) was developed as a possible agent for boron neutron capture therapy. The boron concentration was measured by an in vivo rat experimental brain tumor model and an in vitro cell culture study. This agent was compared to sodium borocaptate (BSH) which has been used in clinical trials of boron neutron capture therapy. In the 9L rat brain tumor model, STA-BX909 achieved a higher boron tumor/blood ratio 24 h after injection in comparison to BSH. A boron concentration study in cultured glioma cell lines (U-251, U-87, 9L) demonstrated an increased boron concentration as a function of exposure time to STA-BX909, while the boron concentration remained stable with increasing exposure time to BSH. Use of a colony forming assay with thermal neutron irradiation revealed more cytotoxicity with STA-BX909 than BSH when the same concentration of 10B was administered. We concluded that STA-BX909 may be an effective drug for use in boron neutron capture therapy and that it merits further investigation.

Animals↗

Evaluation of carborane-containing porphyrins as tumour targeting agents for boron neutron capture therapy.

A number of carborane-containing porphyrins were administered to mice bearing subcutaneously transplanted mammary carcinomas. Administration was via serial intraperitoneal (i.p.) injections to assess their relative toxicities and tumour affinities. Three analogues of the natural porphyrin heme and four tetraphenylporphyrins (TPPs) were given at total doses of 78-245 micrograms g-1 body weight. The water-insoluble TPPs were less toxic to mice, and delivered greater amounts of boron to tumour than did the water-soluble TPPS and the heme analogues. One such compound, NiTCP-H, delivered more than 100 micrograms B g-1 to tumour tissue with a tumour:blood boron concentration ratio greater than 500:1 and a tumour: brain boron concentration ratio greater than 50:1, 4 days after the last of six i.p. injections given over 2 days. Another TPP analogue, NiTCP, delivered approximately 50 micrograms B g-1 to tumour with similar boron concentrations in normal tissues. Neither compound was toxic to mice at total doses of approximately 200 micrograms g-1 body weight. In contrast, the heme analogues were toxic and, with the exception of VCDP, delivered less boron to tumour than NiTCP and NiTCP-H. The two porphyrins with the greatest potential for application to boron neutron capture therapy (BNCT), NiTCP and NiTCP-H, yielded higher tumour:blood and tumour:brain boron concentration ratios in mice than could be achieved with p-boronophenylalanine (BPA) and sodium mercaptoundecahydrododecaborate (BSH), the compounds which are currently being used in clinical trials of BNCT in the treatment of glioblastoma. The boron delivered by each of the porphyrins tested remained in tumour tissue longer than did boron delivered by either BPA or BSH. The copper and nickel chelates of these porphyrins behave identically in vivo. The former offer the potential for imaging by 67Cu-mediated single photon emission computed tomography (SPECT) to aid BNCT treatment planning.

Animals↗

The mapping of natural boron in histological sections of mouse tissues by the use of neutron-capture radiography.

Neutron-capture radiography has been applied to the mapping of natural boron in mouse histological sections. The method is based on the fact that the stable isotope boron-10 has an extremely large cross-section for the thermal-neutron reaction 10B(n, alpha)7Li. The local tissue boron concentrations were evaluated from the corresponding track densities of the nuclear reaction using an equation derived from a theoretical model of the system. The adjustable parameters of this equation were determined in two separate calibration experiments using standardized samples prepared by the addition of known amounts of boron. Interference from other nuclides engaged in nuclear reactions with thermal neutrons was also estimated. In the present experimental conditions the natural boron lower detection limit was 0.03 p.p.m. (fresh weight), and the spatial resolution was of the order of a few micrometers. Boron concentrations in mouse serum and urine were close to 0.22 and 0.57 micrograms ml-1, respectively. In the solid mouse tissues--liver, heart, brain, muscle and spleen--the concentration was usually low, ranging from 0.12 to 0.16 p.p.m. (fresh weight). They were significantly higher in the kidney, especially in the papilla (6.2 p.p.m. fresh weight). Apart from the kidney papilla, where boron was particularly concentrated in wall tubules, the boron distribution in most tissues appeared to be practically homogeneous. Natural boron, and even more so its enriched stable isotope 10B, appear as good candidates for molecular labelling using non-radioactive tracers.

Animals↗

Clinical phase-I study of Na2B12H11SH (BSH) in patients with malignant glioma as precondition for boron neutron capture therapy (BNCT).

PURPOSE: Within the European collaboration on boron neutron capture therapy (BNCT), a clinical Phase I study is being carried out to establish BNCT as an alternative treatment modality for malignant glioma (WHO III/IV). Data about the pharmacokinetics, biodistribution and toxicity of the boron compound Na2B12H11SH (BSH) are of great importance to avoid radiation damage of healthy tissue and to deliver a sufficient radiation dose. METHODS AND MATERIALS: Twenty four patients suffering from a glioblastoma multiforme entered the study to date, infused with a maximum concentration of up to 50 mg BSH/kg. Boron concentration measurements in tissues, urine, and blood were carried out, using inductively coupled plasma-atomic spectroscopy (ICP-AES) and quantitative neutron capture radiography (QNCR). A cross-calibration of these boron determination techniques was carried out. RESULTS: In tumor tissue, confirmed by histopathology of small biopsies, we found a consistently high but heterogeneous boron uptake. Necrotic parts contain much lower amounts of boron; normal brain tissue has shown no significant uptake. In skin, bone, muscle, and dura mater only small amounts of boron were found. In blood samples, we found biphasic kinetics, but with variations of the half-lives from patient to patient. The compound is mainly excreted through the urine, but an additional entero-hepatic pathway can be demonstrated. Systematic investigations revealed no toxic side effect of the intravenously administered BSH. Comparable data were obtained by using ICP-AES and QNCR for boron concentration measurements. CONCLUSION: Taking into account the radiobiological considerations of the neutron beam source, we found promising facts that BNCT could be a useful irradiation method for highly malignant brain tumors. Favorable amounts of the boron compound BSH were found in tumor tissue, whereas healthy brain tissue has shown no significant uptake.

Aged↗

Nucleotide adsorption-desorption behaviour of boronic acid functionalized uniform-porous particles.

In this study, nucleotide adsorption-desorption behaviour of boronic acid-carrying uniform, porous particles was investigated. The particles were produced by a "multi-step microsuspension polymerization" in the form of poly(styrene-vinylphenyl boronic acid-divinylbenzene) terpolymer. In the first step of the production method, uniform polystyrene latex particles (6.2 microm in size) were obtained by dispersion polymerization. These particles were first swollen by a low molecular mass organic agent (i.e. dibutylphthalate, DBP) and then by a monomer mixture including styrene (S), 4-vinylphenyl boronic acid (VPBA) and divinylbenzene (DVB). The particle uniformity was protected in both swelling stages by adjusting DBP/polystyrene latex and monomer mixture/polystyrene latex ratios. Polymerization of the monomer mixture in the swollen seed particles provided boronic acid-carrying uniform, porous particles 11-12 microm in size. To have uniform particles with different porosities and boronic acid contents, the feed concentration of boronic acid-carrying monomer and the monomer/seed latex ratio were changed. The particles were tried as sorbent for the adsorption of a model nucleotide (i.e., beta-nicotinamide adenine dinucleotide, beta-NAD). In the beta-NAD adsorption experiments, the maximum equilibrium adsorption was obtained at pH 8.5 which was very close to pKa of boronic acid. The incorporation of boronic acid functionality provided a significant increase in the beta-NAD adsorption. In contrast to plain poly(styrene-co-divinylbenzene) particles, four-fold higher beta-NAD adsorption was obtained with the boronic acid functionalized particles. Beta-NAD was desorbed from the particles with the yields higher than 90% by weight.

Adsorption↗

Boron supplementation and activated factor VII in healthy men.

OBJECTIVE: The aim of the present study was to determine whether postprandial concentrations of the active component of serine protease coagulation factor VII (VIIa) were lowered by acute boron supplementation in vivo. DESIGN: An acute, randomized, placebo-controlled, double blind, cross-over study. SETTING: Free-living population. SUBJECTS: Fifteen apparently healthy men, aged 45-65 y. INTERVENTIONS: Subjects visited the centre on two occasions, with the study days separated by a minimum of 2 weeks. Following collection of a fasting blood sample, subjects received either placebo or acute bolus of 11.6 mg boron (given as 102.6 mg sodium tetraborate decahydrate) together with a standard fat-rich meal. Blood samples were obtained at 1, 2, 4 and 6 h after the administration of the test meal, during which time subjects were at liberty to consume deionized water only. Blood samples were assayed for concentrations of insulin, glucose, lipids and boron. Measurement of the concentration of activated factor VIIa and of factor VII antigen, and of the activity of coagulation factors VII, IX and X was also carried out. RESULTS: Plasma boron concentrations were significantly higher following consumption of the boron supplement compared with placebo (0.124+/-0.02 vs 0.008+/-0.01 mg/l; P< or =0.001). There was no significant effect of acute boron supplementation on plasma insulin and glucose concentration or on blood lipid or coagulation factor profile. Factor VIIa rose significantly following consumption of the high fat meal (1.05+/-0.07 vs 1.26+/-0.07; P< or =0.001), but this increase was not altered by boron supplementation. CONCLUSIONS: Results from this study suggest that acute boron supplementation (at 11.6 mg boron) does not alter the activity of factor VIIa following consumption of a high-fat meal. SPONSORSHIP: This work was funded by Borax Europe Ltd.

Aged↗