Life Extension Magazine November 2003
Maintains Bones, Joints, Neurons and May Reduce Prostate Cancer Risk
by Stephen B. Strum, M.D., FACP
Medical Oncologist Specializing in Prostate Cancer
CONCLUSIONS ON BORON’S ROLE IN HEALTH AND DISEASE
Boron, the fifth element in the periodic table of elements, has a number of important functions that are worthy of intense clinical attention. Boron is an integrative element supporting the functions of calcium, magnesium, and vitamin D. Boron enhances bone and joint integrity and brain function. The results of a recent study indicate that boron is the most significant element in the prevention of prostate cancer. This finding complements an exciting basic research study showing that boron, an inhibitor of serine proteases such as PSA, lowered PSA and prostate cancer volume significantly. This simple and relatively inexpensive element deserves a major focus of funding in the world of research and clinical medicine.
Stephen B. Strum, M.D. has been a board-certified medical oncologist since 1975. In 2000 he became the first medical director of the Prostate Cancer Research Institute in Los Angeles. Dr. Strum has published widely about prostate cancer as well as other areas to optimize outcomes for those with cancer.
ACRONYM: A word formed from the initial letters of a name, such as BNCT for Boron Neutron Capture Therapy.
ADJUNCT: Something added to another for embellishment or completion.
ADJUVANT: An additional therapy that is added to a primary treatment to increase or aid its effect. Adjuvant therapy is usually given once the primary therapy is completed, e.g., radiation therapy after primary surgery. Neoadjuvant therapy indicates that the additive therapy is given prior to the so-called primary therapy. For example, neoadjuvant androgen deprivation therapy is often used prior to radiation therapy.
COCKEREL: A young rooster.
KILOGRAM (kg): A unit of mass equaling one thousand grams or 2.2 pounds.
MICROGRAM (mcg or mg): A unit of mass equaling one millionth of a gram.
MICRON: A unit of length equal to one millionth of a meter or approximately 1/25,000 of an inch.
MILLIGRAM (mg): A unit of mass equaling one thousandth of a gram.
NOAEL: No-Observed-Adverse-Effect Level. This is an acronym used to categorize toxicity of various drugs, vitamins, and supplements.
PROTEOLYTIC: Having the ability to break down proteins by enzyme actions.
QUARTILE: The value of the boundary at the 25th, 50th, or 75th percentiles of a frequency distribution; this is divided into four parts, each containing a quarter of the population. In a class of 100 students, those 25 students with the highest grades are in the upper quartile of the class, while the 25 with the lowest grades are in the lowest quartile.
1. Zhang Z-F, Winton MI, Rainey C, et al: Boron is associated with decreased risk of human prostate cancer. FASEB J 15:A1089, 2001.
2. Stacewicz-Sapuntzakis M, Bowen PE, Hussain EA, et al: Chemical composi- tion and potential health effects of prunes: a functional food? Crit Rev Food Sci Nutr 41:251-86, 2001.
3. Gallardo-Williams MT, Maronpot RR, King PE, et al: Effects of boron supple- mentation on the morphology, PSA lev- els, and proliferative activity of LNCaP tumors in nude mice. Proc Amer Assoc Cancer Res 43:77, 2002.
4. Murmu N, Ghosh P, Gomes A, et al: Antineoplastic effect of new boron com- pounds against leukemic cell lines and cells from leukemic patients. J Exp Clin Cancer Res 21:351-6, 2002.
5. Sur P, Ghosh P, Bag SP, et al: On the inhibitory activities of a new boron com- pound and ultrasound against the mouse ascites tumour. Chemotherapy 45:360-9, 1999.
6. Ghosh P, Sur B, Bag SP, et al: A new boron compound (guanidine biboric acid adduct) as an antitumour agent against Ehrlich ascites carcinoma in mice. Tumour Biol 20:44-51, 1999.
7. Dibas A, Howard J, Anwar S, et al: Borato-1,2-diaminocyclohexane plat- inum (II), a novel anti-tumor drug. Biochem Biophys Res Commun 270:383- 6, 2000.
8. Hall IH, Elkins A, Powell WJ, et al: Substituted carboranes and polyhedral hydroborate salts as anti-neoplastics. Anticancer Res 18:2617-22, 1998.
9. Hall IH, Elkins AL, Sood A, et al: The cytotoxicity of adenosine 5’-[N,N-di- (gamma-o-carboranyl)propyl] phospho rodiamidate in human Tmolt3 leukemic cells. Anticancer Res 17:151-6, 1997.
10. Webber MM, Waghray A, Bello D: Pro- state-specific antigen, a serine protease, facilitates human prostate cancer cell inva- sion. Clin Cancer Res 1:1089-94, 1995.
11. Nielsen FH: Studies on the relationship between boron and magnesium which possibly affects the formation and main- tenance of bones. Magnes Trace Elem 9:61-9, 1990.
12. Nielsen FH, Hunt CD, Mullen LM, et al: Effect of dietary boron on mineral, estrogen, and testosterone metabolism in post-menopausal women. FASEB J 1:394-7, 1987.
13. Gross C, Stamey T, Hancock S, et al: Treatment of early recurrent prostate cancer with 1,25-dihydroxyvitamin D3 (calcitriol). J Urol 159:2035-9; discussion 2039-40, 1998.
14. Hegsted M, Keenan MJ, Siver F, et al: Effect of boron on vitamin D deficient rats. Biol Trace Elem Res 28:243-55, 1991.
15. 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 12:221-233, 1999.
16. Scharla SH, Minne HW, Waibel-Treber S, et al: Bone mass reduction after estro- gen deprivation by long-acting gonadotropin-releasing hormone ago- nists and its relation to pretreatment serum concentrations of 1,25-dihydrox- yvitamin D3. J Clin Endocrinol Metab 70:1055-61, 1990.
17. US Department of Health and Human Services, Surgeon General’s report on nutrition and health. Rocklin, CA, Prima Publishing and Communications, 1988.
18. Largo R, Alvarez-Soria MA, Diez- Ortego I, et al: Glucosamine inhibits IL-1beta-induced NFkappaB activation in human osteoarthritic chondrocytes. Osteoarthritis Cartilage 11:290-8, 2003.
19. Fenton JI, Chlebek-Brown KA, Caron JP, et al: Effect of glucosamine on interleukin-1-conditioned articular car- tilage. Equine Vet J Suppl:219-23, 2002.
20. Hall IH, Rajendran KG, Chen SY, et al: Anti-inflammatory activity of amine- carboxyboranes in rodents. Arch Pharm (Weinheim) 328:39-44, 1995.
21. Rajendran KG, Chen SY, Sood A, et al: The anti-osteoporotic activity of amine- carboxyboranes in rodents. Biomed Pharmacother 49:131-40, 1995.
22. Hall IH, Starnes CO, McPhail AT, et al: Anti-inflammatory activity of amine cyanoboranes, amine carboxyboranes, and related compounds. J Pharm Sci 69:1025-9, 1980.
23. Newnham RE: Essentiality of boron for healthy bones and joints. Environ Health Perspect 102 Suppl 7:83-5, 1994.
24. Travers RL, Rennie GC, Newnham RE: Boron and arthritis: the result of a dou- ble-blind pilot study. J Nutr Med 1:127- 132, 1990.
25. Helliwell TR, Kelly SA, Walsh HP, et al: Elemental analysis of femoral bone from patients with fractured neck of femur or osteoarthrosis. Bone 18:151-7, 1996.
26. Penland JG: Dietary boron, brain func- tion, and cognitive performance. Environ Health Perspect 102 Suppl 7:65- 72, 1994.
27. Glorioso S, Todesco S, Mazzi A, et al: Double-blind multicentre study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res 5:39-49, 1985.
28. Gaby AR: Natural treatments for osteo- arthritis. Altern Med Rev 4:330-41, 1999.
29. Konig B: A long-term (two years) clini cal trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med 83:89-94, 1987.
30. Ralston NV, Hunt CD: Diadenosine phosphates and S-adenosylmethionine: novel boron binding biomolecules detected by capillary electrophoresis. Biochim Biophys Acta 1527:20-30, 2001.
31. Agdeppa ED, Kepe V, Petri A, et al: In vitro detection of (S)-naproxen and ibuprofen binding to plaques in the Alzheimer’s brain using the positron emission tomography molecular imag ing probe 2-(1-[6-[(2-[(18)F]fluo- roethyl)(methyl)amino]-2- naphthyl]ethylidene)malono nitrile. Neuroscience 117:723-30, 2003.
32. Blasko I, Grubeck-Loebenstein B: Role of the immune system in the pathogen- esis, prevention and treatment of Alzheimer’s disease. Drugs Aging 20:101-13, 2003.
33. Penland JG: The importance of boron nutrition for brain and psychological function. Biol Trace Elem Res 66:299- 317, 1998.
34. Benderdour M, Van Bui T, Hess K, et al: Effects of boron derivatives on extracellular matrix formation. J Trace Elem Med Biol 14:168-73, 2000.
35. Nielsen FH: Ultratrace Minerals. In: Modern Nutrition Health Disease. (9th edition), editor M.E. Shils, Baltimore, MD, Lippincott Williams & Wilkins, 1999, pp. 286-288.
36. Olney JW: Role of excitotoxins in developmental neuropathology. APMIS Suppl 40:103-12, 1993.
37. Fail PA, Chapin RE, Price CJ, et al: General, reproductive, developmental, and endocrine toxicity of boronated compounds. Reprod Toxicol 12:1-18, 1998.
38. Murray FJ: A human health risk assess- ment of boron (boric acid and borax) in drinking water. Regul Toxicol Pharmacol 22:221-30, 1995.
39. Linden CH, Hall AH, Kulig KW, et al: Acute ingestions of boric acid. J Toxicol Clin Toxicol 24:269-79, 1986.
40. Pinto J, Huang YP, McConnell RJ, et al: Increased urinary riboflavin excre tion resulting from boric acid ingestion. J Lab Clin Med 92:126-34, 1978.
41. Gordon AS, Prichard JS, Freedman MH: Seizure disorders and anemia associated with chronic borax intoxica- tion. Can Med Assoc J 108:719-21, 1973.
42. Hubbard SA: Comparative toxicology of borates. Biol Trace Elem Res 66:343- 57, 1998.
43. Pan XQ, Wang H, Shukla S, et al: Boron-containing folate receptor-tar- geted liposomes as potential delivery agents for neutron capture therapy. Bioconjug Chem 13:435-42, 2002.
44. Shukla S, Wu G, Chatterjee M, et al: Synthesis and Biological Evaluation of Folate Receptor-Targeted Boronated PAMAM Dendrimers as Potential Agents for Neutron Capture Therapy. Bioconjug Chem 14:158-67, 2003.
45. Pan XQ, Wang H, Lee RJ: Boron deliv- ery to a murine lung carcinoma using folate receptor-targeted liposomes. Anticancer Res 22:1629-33, 2002.
46. Valliant JF, Schaffer P, Stephenson KA, et al: Synthesis of boroxifen, a nido- carborane analogue of tamoxifen. J Org Chem 67:383-7, 2002.
47. Vicente MG: Porphyrin-based Sensitizers in the Detection and Treatment of Cancer: Recent Progress. Curr Med Chem Anti-Canc Agents 1:175-94, 2001.
48. Hill JS, Kahl SB, Stylli SS, et al: Selective tumor kill of cerebral glioma by photodynamic therapy using a boronated porphyrin photosensitizer. Proc Natl Acad Sci U S A 92:12126-30, 1995.
49. Yamada Y, Toda K, Kahl SB, et al: Enhanced therapeutic effect on murine melanoma and angiosarcoma cells by boron neutron capture therapy using a boronated metalloporphyrin. Kobe J Med Sci 40:25-37, 1994.
50. Shahbazi-Gahrouei D, Williams M, Rizvi S, et al: In vivo studies of Gd- DTPA-mono-clonal antibody and gd- porphyrins: potential magnetic reso nance imaging contrast agents for melanoma. J Magn Reson Imaging 14:169-74, 2001.
51. Kreimann EL, Miura M, Itoiz ME, et al: Biodistribution of a carborane-con- taining porphyrin as a targeting agent for Boron Neutron Capture Therapy of oral cancer in the hamster cheek pouch. Arch Oral Biol 48:223-32, 2003.
52. Miura M, Joel DD, Smilowitz HM, et al: Biodistribution of copper carbo ranyltetraphenylporphyrins in rodents bearing an isogeneic or human neo- plasm. J Neurooncol 52:111-7, 2001.
53. Miura M, Morris GM, Micca PL, et al: Boron Neutron Capture Therapy of a Murine Mammary Carcinoma using a LipophilicCarboranyltetraphenylpor- phyrin. Radiat Res 155:603-610, 2001.
54. Callahan DE, Forte TM, Afzal SM, et al: Boronated protoporphyrin (BOPP): local-ization in lysosomes of the human glioma cell line SF-767 with uptake modulated by lipoprotein levels. Int J Radiat Oncol Biol Phys 45:761-71, 1999.
55. Nichols TL, Kabalka GW, Miller LF, et al: Improved treatment planning for boron neutron capture therapy for glioblastoma multiforme using fluo- rine-18 labeled boronophenylalanine and positron emission tomography. Med Phys 29:2351-8, 2002.
56. Kabalka GW, Nichols TL, Smith GT, et al: The use of positron emission tomog- raphy to develop boron neutron cap- ture therapy treatment plans for metastatic malignant melanoma. J Neurooncol 62:187-95, 2003.
57. Hawthorne MF: Condensed version of the 79th faculty research lecture, Department of Chemistry and Biochemistry at UCLA, 1995
58. Diaz AZ, Coderre JA, Chanana AD, et al: Boron neutron capture therapy for malignant gliomas. Ann Med 32:81-5, 2000.
59. Hawthorne MF, Lee MW: A critical assessment of boron target compounds for boron neutron capture therapy. J Neurooncol 62:33-45, 2003.
60. Hunt CD, Nielsen FH: Dietary boron affects bone calcification in magnesium and chole-calciferol deficient chicks. In: Trace elements in human and animal nutrition. (5th edition), editor W. Mertz, New York, Academic Press, 1986, pp. 275-277.
61. Hunt CD, Nielsen FH: Interaction between boron and cholecalciferol in the chick. In: Trace elements in human and animal nutrition. (4th edition), edi- tor E.J. Underwood, New York, Academic Press, 1977, pp. 597-600.
62. Hunt CD, Herbel JL, Idso JP: Dietary boron modifies the effects of vitamin D3 nutrition on indices of energy sub- strate utilization and mineral metabolism in the chick. J Bone Miner Res 9:171-82,1994.
63. Bai Y, Hunt CD: Dietary boron enhances efficacy of cholecalciferol in broiler chicks. J Trace Elem Exp Med 9:117-132, 1996.
64. Hunt CD: Biochemical effects of physi- ological amounts of dietary boron. J Trace Elem Exp Med 9:185-213, 1996.
65. Nielsen FH, Penland JG: Boron supple- mentation of perimenopausal women affects boron metabolism and indices associated with macromineral metabolism, hormonal status and immune function. J Trace Elem Exp Med 12:251-261, 1999.
66. Hunt CD: The biochemical effects of physiologic amounts of dietary boron in animal nutrition models. Environ Health Perspect 102 Suppl 7:35-43, 1994.
67. Nielsen FH: Boron in human and ani- mal nutrition. Plant and Soil 193:199- 208, 1997.