Biological Trace Element Research

, Volume 143, Issue 3, pp 1223–1238 | Cite as

Calcium Fructoborate—Potential Anti-inflammatory Agent

  • Romulus Ion ScoreiEmail author
  • Petre Rotaru


Calcium fructoborate is a boron-based nutritional supplement. Its chemical structure is similar to one of the natural forms of boron such as bis-manitol, bis-sorbitol, bis-fructose, and bis-sucrose borate complexes found in edible plants. In vitro studies revealed that calcium fructoborate is a superoxide ion scavenger and anti-inflammatory agent. It may influence macrophage production of inflammatory mediators, can be beneficial for the suppression of cytokine production, and inhibits progression of endotoxin-associated diseases, as well as the boric acid and other boron sources. The mechanisms by which calcium fructoborate exerts its beneficial anti-inflammatory effects are not entirely clear, but some of its molecular biological in vitro activities are understood: inhibition of the superoxide within the cell; inhibition of the interleukin-1β, interleukin-6, and nitric oxide release in the culture media; and increase of the tumor necrosis factor-α production. Also, calcium fructoborate has no effects on lipopolysaccharide-induced cyclooxygenase-2 protein express. The studies on animals and humans with a dose range of 1–7 mg calcium fructoborate (0.025–0.175 mg elemental boron)/kg body weight/day exhibited a good anti-inflammatory activity, and it also seemed to have negligible adverse effect on humans.


Boron Calcium fructoborate Osteoporosis Osteoarthritis Anti-inflammatory Antioxidant 


Conflicts of interest

The authors have no relevant interests to declare.

Authors' information

RS is a Professor in the Biochemistry Department, University of Craiova. RP is a Master of Conferences in the Department of Physics, University of Craiova.


  1. 1.
    Miljkovic D (1998) Boron carbohydrates complexes and uses thereof. October 8, US Patent 5962049Google Scholar
  2. 2.
    Miljkovic D, Scorei IR, Cimpoiasu VM et al (2009) Calcium fructoborate: plant-based dietary boron for human nutrition. J Diet Suppl 6:211–226CrossRefGoogle Scholar
  3. 3.
    Scorei RI (2011) Calcium fructoborate: plant-based dietary boron as potential medicine for cancer therapy. Front Biosci S3(1):205–215CrossRefGoogle Scholar
  4. 4.
    Scorei R, Ciubar R, Iancu C, Mitran V et al (2007) In vitro effects of calcium fructoborate on fMLP-stimulated human neutrophil granulocytes. Biol Trace Elem Res 118:27–37PubMedCrossRefGoogle Scholar
  5. 5.
    Scorei RI, Ciofrangeanu C, Ion R et al (2010) In vitro effects of calcium fructoborate upon production of inflammatory mediators by LPS-stimulated RAW 264.7 macrophages. Biol Trace Elem Res 135:334–344PubMedCrossRefGoogle Scholar
  6. 6.
    Scorei R, Cimpoiasu VM, Iordachescu D (2005) In vitro evaluation of the antioxidant activity of calcium fructoborate. Biol Trace Elem Res 107:127–134PubMedCrossRefGoogle Scholar
  7. 7.
    Scorei R, Ciubar R, Ciofrangeanu CM et al (2008) Comparative effects of boric acid and calcium fructoborate on breast cancer cells. Biol Trace Elem Res 122:197–205PubMedCrossRefGoogle Scholar
  8. 8.
    Hunt CD, Herbel JL, Idso JP (1994) Dietary boron modifies the effects of vitamin D, nutrition on indices of energy substrate utilization and mineral metabolism in the chick. J Bone Miner Res 9:171–182PubMedCrossRefGoogle Scholar
  9. 9.
    Scorei R, Popa R (2010) Boron-containing compounds as preventive and chemotherapeutic agents for cancer. Anticancer Agent Med Chem 10:346–351Google Scholar
  10. 10.
    Criste RD, Grossu DV, Scorei R et al (2005) New investigations on the effect of the dietary boron on broilers and layers: boron and food quality. Arch Zoot 8:65–78. Available at Google Scholar
  11. 11.
    Hu H, Penn SG, Lebrilla CB et al (1997) Isolation and characterization of soluble boron complexes in higher plants. Plant Physiol 113:649–655PubMedCrossRefGoogle Scholar
  12. 12.
    Yamaki S (1995) Physiology and metabolism of fruit development: biochemistry of sugar metabolism and compartmentation in fruits. Acta Hort 398:109–120Google Scholar
  13. 13.
    Matsunaga T, Nagata T (1995) In vivo 11B NMR observation of plant tissue. Anal Sci 11:889–892CrossRefGoogle Scholar
  14. 14.
    Wang Z, Quebedeaux B (1997) Effects of water stress on the partitioning of 14C glucose, 14C sucrose and 14C sorbitol in apple shoots. Biotronics 26:73–83Google Scholar
  15. 15.
    Brown PH, Shelp BJ (1997) Boron mobility in plants. Plant Soil 193:85–101CrossRefGoogle Scholar
  16. 16.
    Woods WG (1996) Review of possible boron speciation relating to its essentiality. J Trace Elem Exp Med 9:153–163CrossRefGoogle Scholar
  17. 17.
    Kobayashi M, Matoh T, Azuma JI (1996) Two chains of rhamnogalacturonan II are cross-linked by borate-diol ester bonds in higher plant cell walls. Plant Physiol 110:1017–1020PubMedGoogle Scholar
  18. 18.
    Rotaru P, Scorei R, Hărăbor A et al (2010) Thermal analysis of a calcium fructoborate sample. Thermochim Acta 506:8–13CrossRefGoogle Scholar
  19. 19.
    Söderholm S, Roos YH, Meinander N et al (1999) Raman spectra of fructose and glucose in the amorphous and crystalline states. J Raman Spectrosc 30:1009–1018CrossRefGoogle Scholar
  20. 20.
    Pelmore H, Symons MCR (1986) N.M.R. studies of complexes formed by d-fructose and borate ions in aqueous solution. Carbohyd Res 155:206–211CrossRefGoogle Scholar
  21. 21.
    Kim NH, Kim H-J, Kang D et al (2008) Conversion shift of d-fructose to d-psicose for enzyme-catalyzed epimerization by addition of borate. Appl Environ Microbiol 74:3008–3013PubMedCrossRefGoogle Scholar
  22. 22.
    Tătucu M, Rotaru P, Rău I et al (2010) Thermal behaviour and spectroscopic investigation of some methyl 2-pyridyl ketone complexes. J Therm Anal Calorim 100:1107–1114CrossRefGoogle Scholar
  23. 23.
    Olczak-Kobza M (2004) Synthesis and thermal characterization of zinc(II) di(o-aminobenzoate) complexes of imidazole and its methyl derivatives. Thermochim Acta 419:67–71CrossRefGoogle Scholar
  24. 24.
    Badea M, Olar R, Marinescu D et al (2007) Thermal stability of some new complexes bearing ligands with polymerizable groups. J Therm Anal Calorim 88:317–321CrossRefGoogle Scholar
  25. 25.
    Badea M, Olar R, Marinescu D et al (2008) Thermal stability of new complexes bearing both acrylate and aliphatic amine as ligands. J Therm Anal Calorim 92:205–208CrossRefGoogle Scholar
  26. 26.
    Szunyogová E, Mudronová D, Györyová K et al (2007) The physicochemical and biological properties of zinc(II) complexes. J Therm Anal Calorim 88:355–361CrossRefGoogle Scholar
  27. 27.
    Tian ZR, Voigt JA, Jun Liu J et al (2003) Complex and oriented ZnO nanostructures. Nat Mater 2:821–826PubMedCrossRefGoogle Scholar
  28. 28.
    Bauermann LP, Bill J, Aldinger F (2006) Bio-friendly synthesis of ZnO nanoparticles in aqueous solution at near-neutral pH and low temperature. J Phys Chem B 110:5182–5185PubMedCrossRefGoogle Scholar
  29. 29.
    Kropidłowska A, Rotaru A, Strankowski M et al (2008) Heteroleptic cadmium(II) complex, potential precursor for semiconducting CdS layers. Thermal stability and non-isothermal decomposition kinetics. J Therm Anal Calorim 91:903–909CrossRefGoogle Scholar
  30. 30.
    Rotaru A, Mietlarek-Kropidłowska A, Constantinescu C et al (2009) CdS thin films obtained by thermal treatment of cadmium(II) complex precursor deposited by MAPLE technique. Appl Surf Sci 255:6786–6789CrossRefGoogle Scholar
  31. 31.
    Rotaru A, Constantinescu C, Mândruleanu A et al (2010) Matrix assisted pulsed laser evaporation of zinc benzoate for ZnO thin films and non-isothermal decomposition kinetics. Thermochim Acta 498:81–91CrossRefGoogle Scholar
  32. 32.
    Dumitru MD, Miljkovic D, Scorei RI et al (2010) FT-IR and Raman spectroscopic analysis of a calcium fructoborate sample. Physics AUC 20:113–119Google Scholar
  33. 33.
    Wagner CC, Baran EJ (2008) Easy synthesis of CaB2O4 via pyrolysis of calcium fructoborate. Mater Res 11:493–494Google Scholar
  34. 34.
    Wagner CC, Ferraresi Curotto V, Pis Diez R et al (2008) Experimental and theoretical studies of calcium fructoborate. Biol Trace Elem Res 122:64–72PubMedCrossRefGoogle Scholar
  35. 35.
    Yoshimura K, Mayazaki Y, Sawada S et al (1996) B- NMR studies on complexation of borate with linear and crosslinked polysaccharides. J Chem Soc Faraday Trans 92:651–656CrossRefGoogle Scholar
  36. 36.
    Power PP, Woods WG (1997) The chemistry of boron and its speciation in plants. Plant Soil 193:1–13CrossRefGoogle Scholar
  37. 37.
    Mazurek M, Perlin AS (1963) Borate complexing by 5-membered-ring vic-diols. Can J Chemistry 41:2403–2411CrossRefGoogle Scholar
  38. 38.
    Nielsen FH (1997) Boron in human and animal nutrition. Plant Soil 193:199–208CrossRefGoogle Scholar
  39. 39.
    Nielsen FH (19998) Boron-an overlooked element of potential nutritional importance. Nutr Today 23:4–7CrossRefGoogle Scholar
  40. 40.
    Rainey CJ, Nyquist LA, Christensen RE et al (1999) Daily intake of boron from the American diet. J Amer Dietetic Assoc 99:335–341CrossRefGoogle Scholar
  41. 41.
    Moseman RF (1994) Chemical disposition of boron in animals and humans. Environ Health Perspect 102:113–117PubMedGoogle Scholar
  42. 42.
    Devirian T, Volpe S (2003) The physiological effects of dietary boron. Crit Rev Food Sci Nutr 43:219–223PubMedCrossRefGoogle Scholar
  43. 43.
    Rainey C, Nyquist L (1998) Multicountry estimation of dietary boron intake. Biol Trace Elem Res 66:79–86PubMedCrossRefGoogle Scholar
  44. 44.
    National Academy of Sciences, Institute of Medicine, Food and Nutrition Board (2002a) Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium and zinc. National Academy, WashingtonGoogle Scholar
  45. 45.
    Penn SG, Hu H, Brown PH et al (1997) Direct analysis of sugar alcohol borate complexes in plant extracts by matrix-assisted laser desorption/ionization Fourier transform mass spectrometry. Anal Chem 69:2471–2477PubMedCrossRefGoogle Scholar
  46. 46.
    Bielski RI (2003) Sugar alcohols. In: Lewus FA, Tanner W (eds) Encyclopedia of plant physiology, new series. V13A plant carbohydrates. I. Intercellular carbohydrates. Springer, New York, pp 158–192Google Scholar
  47. 47.
    Fuleki T, Pelayo E, Palabay RB (1994) Sugar composition of varietal juices produced from fresh and stored apples. J Agric Food Chem 42:1266–1275CrossRefGoogle Scholar
  48. 48.
    Suni M, Nyman M, Eriksson NA et al (2000) Carbohydrate composition and content of organic acids in fresh and stored apples. J Sci Food Agric 80:1538–1544CrossRefGoogle Scholar
  49. 49.
    Baker SJ, Ding CZ, Akama T (2009) Therapeutic potential of boron-containing compounds. Future Med Chem 1:1275–1288PubMedCrossRefGoogle Scholar
  50. 50.
    Loomis WD, Durst RM (1992) Chemistry and biology of boron. Biofactors 3:229–239PubMedGoogle Scholar
  51. 51.
    Tate SS, Meister A (1978) Serine-borate complex as a transition-state inhibitor of y-glutamyl transpeptidase. Proc Natl Acad Sci USA 75:4806–4809PubMedCrossRefGoogle Scholar
  52. 52.
    Frantzen F, Grimsrud K, Heggli D-E et al (1995) Protein–boronic acid conjugates and their binding to low-molecular-mass cis-diols and glycated hemoglobin. J Chromatogr B Biomed Appl 670:37–45PubMedCrossRefGoogle Scholar
  53. 53.
    Holak W (1971) Atomic absorption determination of boron in foods. J Assoc Off Anal Chem 54:1138–1139PubMedGoogle Scholar
  54. 54.
    Holak W (1971) Collaborative study of the determination of boric acid in foods by atomic absorption spectrophotometry. J Assoc Off Anal Chem 55:890–891Google Scholar
  55. 55.
    Zittle CA (1951) Reaction of borate with substances of biological interest. Adv Enzymol 12:493–527Google Scholar
  56. 56.
    Dupre JN, Keenan MJ, Hegsted M et al (1994) Effects of dietary boron in rats fed a vitamin D-deficient diet. Environ Health Perspect 102:55–58PubMedGoogle Scholar
  57. 57.
    Nielsen FH, Shuler TR, Gallagher SK (1990) Effects of boron depletion and repletion on blood indicators of calcium status in humans fed a magnesium-low diet. J Trace Elem Exp Med 3:45–54Google Scholar
  58. 58.
    Hunt CD (1989) Dietary boron modified the effects of magnesium and molybdenum on mineral metabolism in the cholecalciferol-deficient chick. Biol Trace Elem Res 22:201–220PubMedCrossRefGoogle Scholar
  59. 59.
    Meacham SL, Taper LJ, Volpe SL (1994) Effects of boron supplementation on bone mineral density and dietary, blood, and urinary calcium, phosphorus, magnesium, and boron in female athletes. Environ Health Perspect 102:79–82PubMedGoogle Scholar
  60. 60.
    Nielsen FH (1994) Biochemical and physiologic consequences of boron deprivation in humans. Environ Health Perspect 102:59–63PubMedGoogle Scholar
  61. 61.
    Nielsen FH, Shuler TR, Zimmerman TJ et al (1998) Magnesium and methionine deprivation affect the response of rats to boron deprivation. Biol Trace Elem Res 17:91–107CrossRefGoogle Scholar
  62. 62.
    Nielsen FH, Hunt CD, Mullen LM et al (1987) Effect of dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women. FASEB J 1:394–397PubMedGoogle Scholar
  63. 63.
    Hunt CD (1998) Regulation of enzymatic activity: one possible role of dietary boron in higher animals and humans. Biol Trace Elem Res 66:205–225PubMedCrossRefGoogle Scholar
  64. 64.
    Benderdour M, Van Bui T, Hess K (2000) Effects of boron derivatives on extracellular matrix formation. J Trace Element Med Biol 14:168–173CrossRefGoogle Scholar
  65. 65.
    Turner CP, Toye AM, Jones OTG (1998) Keratinocyte superoxide generation. Free Radical Biol Med 24:401–407CrossRefGoogle Scholar
  66. 66.
    Hunt DC, Idso JP (1999) Dietary boron as a physiological regulator of the normal inflammatory response: a review and current research progress. J Trace Elem Exp Med 12:221–233CrossRefGoogle Scholar
  67. 67.
    Kettritz R, Falk RJ, Jennette JC et al (1977) Neutrophil superoxide release is required for spontaneous and fMLP-mediated but not for TNFα-mediated apoptosis. J Am Soc Nephrol 8:1091–1100Google Scholar
  68. 68.
    Granfeldt D, Samuelsson M, Karlsson A (2002) Capacitative Ca2+ influx and activation of the neutrophil respiratory burst. Different regulation of plasma membrane- and granule-localized NADPH-oxidase. J Leukoc Biol 71:611–617PubMedGoogle Scholar
  69. 69.
    Uchimura K, Nagasaka A, Hayashi R et al (1999) Changes in superoxide dismutase activities and concentrations and myeloperoxidase activities in leukocytes from patients with diabetes mellitus. J Diabet Comp 13:264–270CrossRefGoogle Scholar
  70. 70.
    Zychlinsky A, Fitting C, Cavaillon JM et al (1994) Interleukin 1 is released by murine macrophages during apoptosis induced by Shigella flexneri. J Clin Invest 94:1328–1332PubMedCrossRefGoogle Scholar
  71. 71.
    Cao J, Jiang L, Zhang X et al (2008) Boric acid inhibits LPS-induced TNF-alpha formation through a thiol-dependent mechanism in THP-1 cells. J Trace Elem Med Biol 22:189–195PubMedCrossRefGoogle Scholar
  72. 72.
    Armstrong TA, Spears JW, Lloyd KE (2001) Inflammatory response, growth, and thyroid hormone concentrations are affected by long-term boron supplementation in gilts. J Anim Sci 79:1549–1556PubMedGoogle Scholar
  73. 73.
    Armstrong TA, Spears JW (2003) Effect of boron supplementation of pig diets on the production of tumor necrosis factor-alpha and interferon-gamma. J Anim Sci 81:2552–2561PubMedGoogle Scholar
  74. 74.
    Benderdour M, Hess K, Dzondo-Gadet M et al (1998) Boron modulates extracellular matrix and TNFα synthesis in human fibroblasts. Biochem Biophys Res Commun 246:746–751PubMedCrossRefGoogle Scholar
  75. 75.
    Benderdour M, Hess K, Dzondo-Gadet M et al (1997) Effect of boric acid solution on cartilage metabolism. Biochem Biophys Res Commun 234:263–268PubMedCrossRefGoogle Scholar
  76. 76.
    Pradervand S, Maurya MR, Subramaniam S (2006) Identification of signaling components required for the prediction of cytokine release in RAW 264.7 macrophages. Genome Biol 7:R11PubMedCrossRefGoogle Scholar
  77. 77.
    Calder PC (2003) N–3 polyunsaturated fatty acids and inflammation: from molecular biology to the clinic. Lipids 38:343–352PubMedCrossRefGoogle Scholar
  78. 78.
    Rees D, Miles EA, Banerjee T et al (2006) Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am J Clin Nutr 83:331–342PubMedGoogle Scholar
  79. 79.
    Hardardóttir I, Kinsella JE (1992) Increasing the dietary (n–3) to (n–6) polyunsaturated fatty acid ratio increases tumor necrosis factor production by murine resident peritoneal macrophages without an effect on elicited peritoneal macrophages. J Nutr 122:1942–1951PubMedGoogle Scholar
  80. 80.
    Ferrucci L, Cherubini A, Bandinelli S et al (2006) Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. J Clin Endocrinol Metab 91:439–446PubMedCrossRefGoogle Scholar
  81. 81.
    Nielsen FH (2003) Does boron have an essential function similar to an omega-3 fatty acid function? In: Anke, M, Muller R, Schafer U, Stoeppler M (eds) 21st Workshop on Macro and Trace elements, Friedrich Schiller University, Jena, Germany, October 18–19. Schubert, Leipzig, pp 1238–1250Google Scholar
  82. 82.
    Nathan C, Xie QW (1994) Nitric oxide syntheses. Roles, tolls, and controls. Cell 78:915–918PubMedCrossRefGoogle Scholar
  83. 83.
    Albina JE, Cui S, Mateo RB et al (1993) Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J Immunol 150:5080–5085PubMedGoogle Scholar
  84. 84.
    van den Berg R, Peters JA, van Bekkum H (1994) The structure and (local) stability constants of borate esters of mono- and di-saccharides as studied by 11B and 13C NMR spectroscopy. Carbohydr Res 253:1–12PubMedCrossRefGoogle Scholar
  85. 85.
    Luan Q, Desta T, Chehab L et al (2008) Inhibition of experimental periodontitis by a topical boron-based antimicrobial. J Dent Res 87:148–152PubMedCrossRefGoogle Scholar
  86. 86.
    Mattingly LH, Ruth A, Gault M et al (2007) Use of systemic proteasome inhibition as an immune modulating agent in disease. Endocr Metab Immune Disord Drug Targets 7:29–34PubMedGoogle Scholar
  87. 87.
    Nielsen FH (2008) Is boron nutritionally relevant? Nutr Rev 66:183–191PubMedCrossRefGoogle Scholar
  88. 88.
    Nielsen FH, Mullen LM, Nielsen EJ (1991) Dietary boron affects blood cell counts and hemoglobin concentrations in humans. J Trace Elem Exp Med 4:211–223Google Scholar
  89. 89.
    Travers RL, Rennie GC, Newnham RE (1990) Boron and arthritis: the result of a double-blind pilot study. J Nutr Med 1:127–132CrossRefGoogle Scholar
  90. 90.
    Newnham RE (1994) The role of boron in human nutrition. J Appl Nutr 46:81–85Google Scholar
  91. 91.
    Nielsen FH (2004) Dietary fat composition modifies the effect of boron on bone characteristics and plasma lipids in rats. Biofactors 20:161–170PubMedCrossRefGoogle Scholar
  92. 92.
    Amstrong TA, Spears JVV, Crenshaw TD et al (2000) Boron supplementation of a semipurified diet for weanling pigs improves feed efficiency and bone strength characteristics and alters plasma lipid metabolites. J Nutr 130:2575–2581Google Scholar
  93. 93.
    Richart T, Li Y, Staessen J (2007) Renal versus extra renal activation of vitamin D in relations to atherosclerosis, arterial stiffening and hypertension. Am J Hypetens 20:1007–1015CrossRefGoogle Scholar
  94. 94.
    Bord S, Horner A, Beeton CA et al (1999) Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) distribution in normal and pathological human bone. Bone 24:229–235PubMedCrossRefGoogle Scholar
  95. 95.
    Spector TD, Hart DJ, Nandra D, Doyle et al (2005) Low-level increases in serum C-reactive protein are present in early osteoarthritis of the knee and predict progressive disease. Arthritis Rheum 40(4):723–727CrossRefGoogle Scholar
  96. 96.
    Dessein PH, Stanwix AE (2001) Inflammatory arthritis and cardiovascular disease may share a common predisposition. Rheumatology 40:703–704PubMedCrossRefGoogle Scholar
  97. 97.
    Khovidhunkit W, Kim M, Memon R et al (2004) Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res 45:1169–1196PubMedCrossRefGoogle Scholar
  98. 98.
    Ridker PM, Rifai N, Rose L et al (2009) Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 347:1557–1565CrossRefGoogle Scholar
  99. 99.
    An WS, Kim SE, Kim KH et al (2009) Associations between oxidized LDL to LDL ratio, HDL and vascular calcification in the feet of hemodialysis patients. J Korean Med Sci 24:115–120CrossRefGoogle Scholar
  100. 100.
    World Health Organization (2010) International clinical trials registry platform search portal. Identifier ISRCTN46679573. A double-blind, placebo-controlled pilot study to evaluate calcium fructoborate effect on systemic inflammation and dyslipidaemia markers in middle-aged people with primary osteoarthritis. World Health Organization, Geneva. Available at

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Authors and Affiliations

  1. 1.Department of BiochemistryUniversity of CraiovaCraiovaRomania
  2. 2.Department of Physics II, Faculty of PhysicsUniversity of CraiovaCraiovaRomania

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