Life Extension Magazine®

Issue: Nov 2003

Boron Report

This inexpensive mineral has long been known to help preserve bone mass. New research reveals a system-wide benefit that includes shrinking prostate tumor volume, lowering PSA levels and reducing prostate cancer risk.

Maintains Bones, Joints, Neurons and May Reduce Prostate Cancer Risk
by Stephen B. Strum, M.D., FACP
Medical Oncologist Specializing in Prostate Cancer

As our knowledge of biological systems has increased over the past ten years, a greater understanding of the importance of cellular communication and balance has been reached. The integrative nature of medicine, so characteristic of biological orchestration, has now come to embrace the use of substances that a few decades ago were hardly recognized as important to human health.

Coenzyme Q10, acetyl L-carnitine, alpha lipoic acid, lycopene, selenium, and gamma tocopherol are a few examples of new players in the biologic symphony. Boron can now be added to our list of vital nutrients in the orchestration of health.

While boron has long been known to promote healthy bone density, new research shows that it can shrink prostate tumor size, lower PSA, and may help to prevent prostate cancer. Additional findings show that boron alleviates joint discomfort and preserves cognitive function. The good news is that this low-cost mineral has been added to the most popular supplements that Foundation members are already taking.


Boron reduces prostate cancer incidence by up to 64%
In a study by Zhang et al, men who ingested the greatest amount of boron were 64% less likely to develop prostate cancer (PC) compared to men who consumed the least amount of boron (see Figure 1). This information was presented at the annual Experimental Biology conference in Florida in 2001.1 The study, from the Cancer Epidemiology Training Program at the UCLA School of Public Health, compared dietary patterns of 76 men with prostate cancer to that of 7,651 males without cancer. The greater the quantity of boron-rich foods consumed, the greater the reduction in risk of being diagnosed with prostate cancer. Those men consuming the most boron (i.e., in the upper quartile of boron consumption) had a 64% reduction in prostate cancer, while men in the second quartile had a 35% reduction in risk and those in the third quartile reduced their risk by 24%. Men in the lowest quartile of boron consumption ate roughly one slice of fruit per day, while those in the highest quartile consumed 3.5 servings of fruit per day plus one serving of nuts. Boron-rich foods include plums, grapes, prunes, avocados, and nuts such as almonds and peanuts. A serving of 100 grams of prunes (12 dried prunes) has 2-3 mg of boron and 6.1 grams of fiber.2

FIGURE 1. Lower Prostate Cancer Risk Associated with Boron Consumption.
Those men consuming the most boron had the greatest protective effect against the development of prostate cancer. Sources of boron include non-citrus fruits like dried prunes, plums, grapes, raisins, nuts such as almonds and peanuts, red wine, and coffee. No protective effect of boron was noted against breast, colorectal, uterine, cervical, or skin cancers.18

Boric acid acts to inhibit serine proteases—it decreases PSA by 87% and reduces tumor size in a prostate cancer mouse model
The mechanism of boron’s effect on reducing prostate cancer incidence in the study by Zhang et al previously cited is not known. However, a preliminary report on the effect of boric acid (boron) solutions given to mice bearing the human prostate cancer cell-line called LNCaP may shed some light on this mechanism. In a study published in the 2002 Proceedings of the American Association of Cancer Research, Gallardo-Williams et al indicated that mice receiving 1.7 or 9.0 mg/kg/day of boric acid solution orally had decreases in tumor size by 38% and 25%, respectively.3 The same groups had drops in PSA (prostate-specific antigen) of 88.6% and 86.4%, respectively. The control group receiving only water had no drop in PSA or decrease in tumor size.

Additional findings of interest included a decreased amount of mitoses in the mice treated with boric acid compared to the control group. Mitoses reflect chromosomes or genetic material that are in the process of cell division. Mitotic figures can be seen using a conventional microscope; the greater the number of mitoses, the greater the intensity of cell division and tumor growth (see Figure 2). The authors also found that the histochemical expression of IGF-1 (insulin-like growth factor type 1) was markedly reduced by boron treatment. Circulating blood levels of IGF-1 were not reduced in the treated mice, however.

FIGURE 2: Mitoses in Prostate Cancer Biopsy. Mitoses (also called mitotic figures) may be easily found using the light microscope. If mitoses are abundant in number, it can be presumed that the proliferative rate of the tumor is high. High mitotic rates are seen with more aggressive histologic grades of prostate cancer.

This study by Gallardo-Williams is of potentially great significance and the rationale for such a study merits further discussion. The authors’ evaluation of boric acid was based on a hypothesis that relates to the important finding that PSA is not only a biomarker of prostate cancer activity but also a functional enzyme produced by prostate cancer cells that acts to promote its very own tumor growth.10 My interpretation of their hypothesis is as follows:

  • PSA is an enzyme (a serine protease) that frees IGF-1 from insulin-like growth factor binding protein.
  • IGF-1 has been shown to promote the growth of prostate cancer.
  • A reduction in PSA’s enzymatic activity should decrease the amount of IGF-1. This in turn should decrease prostate cancer growth.
  • Boric acid is a known inhibitor of several serine proteases.
  • Blood boric acid levels as low as 8 mcg/ml can inhibit the proteolytic activity of PSA (authors’ separate work).
  • Boric acid administration should therefore reduce PSA.
  • This reduction of PSA should be accompanied by decreased expression of IGF-1 and decreased tumor growth.

This report apparently has led to further clinical trials now in progress.

The anti-cancer effect of boron compounds has been the subject of prior studies that involved tumor cell lines of human malignancies grown in culture. These studies are summarized in Table 1.

Cancer Cell Type(s) Effect on Tumor Cell
Boron Compound(s) Reference

Acute lymphocytic leukemiaChronic lymphocytic leukemia

Growth inhibition after treatment with boron compounds

dihydroxy (oxybiguanido) boron (iii) hydrochloride monohydrate (HB)

guanidine biboric acid adduct (GB)

hydroxosalicyl hydroxomato boron (iii) (SHB)


Ehrlich ascites tumor

Significant anti-tumor action that was further increased by combining with ultrasound therapy

dihydroxy (oxybiguanido) boron (III) hydrochloride monohydrate


Ehrlich ascites tumor

Significantly increased survival time

guanidine biboric acid adduct (GB)


L1210 murine leukemia cellsDU-145 prostate
cancer cellsA549 lung
carcinoma cellsMCF-7 breast
cancer cells

inhibited DNA synthesis

Borato-1,2-diaminocyclohexane platinum (II) (BDP)


LNCaP prostate
cancer cells

Reduced PSA by 86-89% and reduced tumor volume by 25-38%; mitoses and IGF-1 decreased in tissue studies

Boric acid solution


Mouse and human leukemiasHuman uterine,
colon, and lung
adenocarcinomasHuman gliomas

Inhibited growth

Amino-o-carborane-hydrochloride 7


Murine and human leukemia Uterine carcinoma tumor cell lines

Potent in vivo antineoplastic activity and in vitro cytotoxicity

Adenosine 5’[N,N-di-(gamma-o-carboranyl)propyl] phosphorodiamidate 1


TABLE 1. Anti-Cancer Activity of Boron. Studies of the anti-cancer efficacy of a number of boron compounds against a wide range of tumor cell lines (shown above) warrant clinical trials in humans.


Calcium-Magnesium <=> Boron Interactions
A large number of experiments conducted in humans involving boron supplementation or deprivation show that boron is vitally involved in bone metabolism. It is well accepted that calcium and magnesium are important constituents or building blocks of healthy bone. In situations of adequate calcium supply but deficient magnesium resources, boron appears to substitute or “pinch hit” for magnesium during the process of bone formation. Under such conditions, the concentration of boron within bone tissue increases.

Boron’s effect on bone appears to be mediated by its ability to reduce the urinary excretion of calcium and also magnesium. In situations where adequate boron intake rather than boron depletion prevails, the net effect of boron is to raise ionized calcium levels. This effect of boron—to preserve calcium and decrease urinary losses of calcium—is caused by its actions on the kidney.

As stated above, this calcium-preserving effect of boron becomes pronounced in circumstances in which dietary magnesium is low. With this biologic effect, boron is acting as a backup system to preserve calcium in the blood and reduce urinary calcium loss. In effect, boron acts literally and figuratively as a “bodyguard” to preserve calcium and magnesium in situations of nutritional stress that would otherwise adversely affect metabolic processes involved with these substances.11

Maintains Bones, Joints, Neurons and May Reduce Prostate Cancer Risk
by Stephen B. Strum, M.D., FACP
Medical Oncologist Specializing in Prostate Cancer

The effect of boron intake was analyzed in a human study involving 12 post-menopausal women not on estrogen replacement therapy. Patients were first given a boron-deficient diet consisting of 0.25 mg of boron daily for 119 days. This was followed by a 48-day period in which the same patients received boron supplementation at a dose of 3 mg per day. Patients were also studied during periods of adequate magnesium intake versus magnesium deficiency. Deprivation of boron and/or magnesium caused changes that are similar to those seen in women with post-menopausal osteoporosis, including increased loss of urinary calcium. However, in women receiving 3 mg of boron per day, urinary losses of both calcium and magnesium were significantly diminished, especially if dietary magnesium was low. Also noted were increased levels of plasma ionized calcium, beta estradiol, and testosterone.12

Vitamin D <=> Boron Interactions
Boron manifests additional integrative effects on bone metabolism in its actions relating to vitamin D (cholecalciferol). Vitamin D affects absorption and utilization of calcium and also has major anti-cancer effects relating to slowing tumor cell proliferation.13 Vitamin D enhances calcium absorption through the stomach and small intestine. The effect of boron on raising plasma calcium levels may, in part, be due to its enhancing effect on vitamin D.14 Again, boron is acting as a helper, backup agent, and/or facilitator to maintain bone integrity in its actions on vitamin D and calcium.


The inhibition of enzymes such as serine proteases (e.g., PSA) was mentioned in relation to the anti-cancer effects of boron. In a review of the literature on boron’s metabolic activities, Hunt et al also emphasized the down-regulation of other enzyme activities by boron.15 For example, boron has been shown to inhibit cyclooxygenase (COX) and lipoxygenase (LOX). These two enzymes mediate the inflammatory cascade and are pertinent to therapies directed against inflammatory conditions. Such anti-inflammatory capabilities of boron are clearly pertinent to its anti-cancer effect, because the reduction of COX II and LOX enzymes leads to a decrease in prostaglandin E2 (PGE2) and other unfavorable eicosanoids such as leukotrienes. These hormonal breakdown products of arachidonic acid were discussed and illustrated in an article on prostate cancer in the June 2003 Life Extension magazine. We now know that omega-6 fatty acid metabolism that is allowed to continue down this pathway represents a vital stimulus for angiogenesis and cancer growth.

The very same prostaglandins and leukotrienes are mediators of inflammatory conditions such as degenerative joint disease and osteoarthritis. PGE2 and leukotrienes have been implicated in causing problems with joint swelling, restricted joint motion, and other arthritic complaints. Anti-arthritic agents like glucosamine sulfate work through inhibition of COX II and PGE2 by suppressing nuclear factor kappa beta (NfkappaB)—a proinflammatory cytokine.18,19 There is also evidence that boron has similar modes of action in reducing arthritic conditions.20-22 These findings are clinically supported by evidence showing that areas of the world with low levels of boron in the soil have a higher percentage of people suffering from arthritis in comparison to regions with higher soil levels of boron. There is also epidemiologic evidence that in areas of the world where boron intake is 1 mg or less per day, the estimated incidence of arthritis ranges from 20% to 70%, whereas in areas of the world where boron intake is usually 3-10 mg, the estimated incidence of arthritis ranges from 0 to 10%.23 In a study of 20 patients with osteoarthritis, the 50% who received a daily supplement of 6 mg of boron noted subjective improvement (less pain on movement), while only 10% of those who had received placebo improved over the same time interval.24

Sources of Boron
Boron is a trace mineral that is found in non-citrus fruits such as plums, red grapes, apples, pears, and avocados, as well as in legumes and nuts. It is also present in significant amounts in coffee and red wine. Dried fruits contain a much higher amount of boron than fresh fruit. For example, fresh plums contain 0.45 mg of boron per 100 grams (g), but the same weight of dried prunes (about 12 prunes) contains 2.15 mg of boron.1 Although boron currently is not considered an essential element in the diet of humans, many scientists believe it merits the status as an essential “ultratrace” element.35 The usual dietary boron consumption in humans is 1-2 mg/day for adults. But boron requirements may be as high as 9-12 mg per day.

In another study, bone adjacent to joints with osteoarthritis tends to be less mineralized than control bone and bone from fracture patients. Interestingly, bone samples in such instances have significantly lower concentrations of boron.25

Lastly, there have been studies that show the anti-arthritic effects of S-adenosylmethionine (SAMe) are equivalent to those seen with non-steroidal anti-inflammatory agents (NSAIDs) but without the toxicity seen with NSAIDs.27-29 Also interesting is a report indicating a very high affinity of SAMe for boron.30 An interesting consideration would be to evaluate the efficacy of SAMe in reducing arthritic symptoms in relationship to boron consumption and boron blood levels.


There are many parallels between the medical applications of NSAIDs and the biological properties of boron. These shared benefits may be due to the common mechanisms involved in the down-regulation of pro-inflammatory cytokines and the subsequent reduction in COX II and LOX enzymes. These mechanisms provide some explanation for the positive clinical benefits of boron such as those seen in patients with arthritis and boron’s relation to the reduction in the incidence of prostate cancer, and hopefully in the use of boron in prostate cancer treatment. Since it is now commonly accepted that the routine use of NSAIDs significantly reduces the incidence of Alzheimer’s disease,31,32 it is not surprising that papers have been published on boron’s positive effect on cognitive function.33

Penland et al conducted experiments in men and women to investigate the functional role of boron in relation to brain electrophysiology and cognitive performance (see Table 2). Findings were compared in healthy older men and women while on a diet deprived of boron versus a diet with ample boron (approximately 0.25 mg boron/2000 kcal/day versus approximately 3.25 mg boron/2000 kcal/day). The ability of patients to perform skills involving cognition and psychomotor tasks were assessed and showed significant impairment during the boron-deprived diet. Brain-wave patterns were evaluated using an electroencephalogram (EEG) and showed an increased proportion of low-frequency activity in patients on the boron-deprived diet. Similar findings are often observed in response to general malnutrition and heavy metal toxicity. The authors concluded from such data that boron appears to play a significant role in human brain function and cognitive performance, and that boron is an essential nutrient for humans.26


Boric acid solution (3%) dramatically improves wound healing through action on the extracellular matrix, a finding that has been obtained in vitro.34

Function Studied

Boron-deprived Diet

Boron-ample Diet

p value

Manual dexterity
Eye-hand coordination
Encoding and short-term memory
Long-term memory




Electroencephalogram (EEG)
spectral analysis




Low-frequency activity




High-frequency activity



TABLE 2: Effects of Boron Deprivation on Cognitive Performance and Brain Activity. In multiple studies, older men and women showed statistically significant impairment in cognitive function on a low-boron diet in comparison to a diet ample in boron. EEG activity was also abnormal in patients on the low-boron diet.26


In the 1870s, it was determined that sodium borate (borax, a form of boron) had the ability to preserve foods. Over the next 50 years, borates were valued as preservatives and used to extend the palatability of fish, meat, cream, and butter.35 The first evidence of the potential for toxicity associated with borate consumption occurred in 1904. Human volunteers, consuming over 500 mg per day of boric acid, had symptoms of decreased appetite, nausea, abdominal discomfort, and diarrhea. After this was reported, the use of boron as a food preservative and taste enhancer greatly declined, and by the mid-1950s boron was essentially banned worldwide in the food industry. Ironically, boron has been replaced with monosodium glutamate that has been shown to be neurotoxic36 yet remain in widespread use.

Boron compounds are toxic to all species tested at high doses, but they are not carcinogenic or mutagenic.37 A rat developmental toxicity study of boron determined a “no observed adverse effect level (NOAEL) of 9.6 mg of boron per kg per day. Toxicology studies of boron in humans have shown safety up to a maximal daily intake of 0.3 mg/kg of boron, which equates with a daily intake of 18 mg of boron for a 60-kg (132-pound)individual.38

Four patients with elevated serum boric acid levels after single, acute ingestions of 10-297 grams were reported to the Rocky Mountain Poison and Drug Center (RMPDC) between January 1983 and August 1985. In these cases, systemic effects were absent. In 1983-4, 364 cases of boric acid exposure were reported to the RMPDC, with only one fatality from a probable chronic ingestion. In this case, vomiting, nausea, diarrhea, and abdominal cramps were present. These observations suggest that significant poisoning is unlikely to result from a single, acute ingestion of boric acid.39

A report by Pinto et al showed that boric acid ingestion can induce urinary losses of vitamin B2 (riboflavin).40 Patients taking boron supplements may wish to also consider B vitamin supplementation. Gordon et al reported a case of two infants using pacifiers dipped in a honey-borax solution over a period of several weeks in 1973. These infants had findings of hair loss, anemia, and seizures. All signs and symptoms disappeared after discontinuation of the borax and honey preparation.41

The critical effects of boron in several species involve male reproductive toxicity and developmental toxicity. Testicular effects occurred at approximately 26 milligrams of boron equivalents per kilogram of body weight per day. Data on endocrine toxicity include altered follicle stimulating hormone and testosterone levels within 14 days of treatment.37 It is important to emphasize that the doses that cause these effects are far higher than the levels to which the human population could be exposed. Humans would need to consume daily approximately 3.3 grams of boric acid (or 5.0 grams of borax) to ingest the same dose level as the lowest animal NOAEL. No effects on fertility were seen in a population of workers exposed to borates or to a population exposed to high environmental borate levels.42 Therefore, the likelihood of boron toxicity caused by boric acid and inorganic borates is remote.

Maintains Bones, Joints, Neurons and May Reduce Prostate Cancer Risk
by Stephen B. Strum, M.D., FACP
Medical Oncologist Specializing in Prostate Cancer


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.

Subscribe to Life Extension Magazine®

Subscribe Now

Advertise in Life Extension Magazine®

Learn More