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Boron

Common Name(s): Borate, Borax sodium, Boric acid, Boric anhydride, Boric tartrate, Boron

Clinical Overview

Use

Boron has been included in nutritional supplements or natural remedies designed to improve bone and joint health. Boron deficiency has been shown to impair brain function, inflammatory regulation, and immune response, and to increase the risk of some cancers. However, there is no evidence that boron supplementation above the levels derived in a normal diet is beneficial. Therefore, supplementation is likely to only be useful when dietary intake is inadequate. Boron compounds are also used to enhance the cell selectivity of radiation therapy and may lead to a new generation of drugs. Boric acid, a common form of boron not to be confused with boron, has been used traditionally as a topical astringent, a mild topical anti-infective, ophthalmological irrigant, rodent repellent, and insecticide. Boric acid has also been administered intravaginally for recurrent and resistant vulvovaginal candidiasis.

Dosing

An acceptable safe oral boron intake for adults could be between 1 and 20 mg/day. Tolerable upper intake levels (UL) for boron are: adults 19 years and older, 20 mg/day; adolescents 14 to 18 years of age, 17 mg/day; children 9 to 13 years of age, 11 mg/day; children 4 to 8 years of age, 6 mg/day; children 1 to 3 years of age, 3 mg/day. For the treatment of vulvovaginal candidiasis, boric acid intravaginally 600 mg once or twice daily for 2 weeks has been used; for the prevention of recurring vulvovaginal candidiasis boric acid intravaginally 600 mg twice weekly has been used.

Contraindications

Intravaginal boric acid has been associated with birth defects in the first 4 months of pregnancy.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking, but when boron is used orally at doses below UL, it is likely to be safe. Boric acid should not be used in pregnancy. Intravaginal boric acid has been associated with birth defects in the first 4 months of pregnancy.

Interactions

None well documented.

Adverse Reactions

There is little clinical data concerning adverse effects of boron when used at doses less than UL. As noted above, boric acid administration intravaginally during the first 4 months of pregnancy has been associated with increased risk for birth defects.

Toxicology

Although boric acid, borates, and other compounds containing boron are used medicinally, they can be toxic if ingested at high doses or absorbed through nonintact skin.

Source

The element boron (B, atomic number 5) is found in deposits in the earth's crust at a concentration of about 0.001% (10 ppm). Seawater contains an average of 4.6 ppm boron, ranging from 0.5 to 9.6 ppm. Boron content in fresh water ranges from less than 0.01 to 1.5 ppm, with higher concentrations in regions of high soil boron levels.Woods 1994 It is obtained in the form of various compounds and never in its elemental state.O'Neil 2006

Since 1857, it has been known that environmental boron is taken up by plants in trace amounts, and in 1923, boron was recognized as an essential nutrient for plants.Devirian 2003 Accordingly, plants contribute to dietary boron intake, with primary sources being fruits, nuts, and vegetables.Devirian 2003 Good sources of boron include peanuts, peanut butter, almonds, hazelnuts, seaweed, soybeans, parsley, cocoa, wine, raisins, prunes, apples, and peaches.Devirian 2003, Choi 2008, Rainey 1999, Jamison 2003

Boron was originally obtained in 1895 from the reduction of boric anhydride, which remains a commercially important way to produce impure boron today. Pure boron takes the form of clear red or black crystals, depending on its crystalline shape.O'Neil 2006 The crystals can be as hard as diamonds. The chemistry of boron is extremely complex, with entire texts devoted solely to this topic.

History

Reports suggest the Babylonians used borax as flux for working gold 4,000 years ago; this is also recognized in the Saudi Arabian area of Mecca and Medina in the 8th century and by European goldsmiths in the 12th century.Woods 1994 Boron was used as a food preservative between 1870 and 1920 and during World War I and II.Nielsen 2008

Borate-mineral concentrates, borax, boric acid, and other refined products have been used in glass, fiberglass, and washing products, and in combination with other metals to make harder alloys, fertilizers, wood treatments, insecticide, rodent repellant, and antimicrobial.Woods 1994 As an insect and rodent repellent, boric acid was sprinkled in corners and along floor boards; however, this practice should be avoided because of the serious toxicity that can occur if ingested by small children or pets.

Boron is used in nuclear medicine and chemistry as a neutron absorber.

Uses and Pharmacology

Although no clear biological function for boron has been established in humans, evidence from numerous laboratories using a variety of experimental models shows that boron is a beneficial bioactive elementNielsen 2008 referred to by some as an ultratrace mineral.Jamison 2003, Nielsen 2008 It is postulated that it may even be essential to humans.Mastromatteo 1994, Nielsen 2009

The evidence includes deprivation studies showing that boron is necessary for some higher animals to complete their life cycle (eg, frogs,Fort 1999, Fort 2002 zebrafish).Rowe 1999 However, critical experiments demonstrating that boron is essential for a complete mammal life cycle or as an essential biochemical role for life are lacking.Nielsen 2008

In higher animals, low boron intake (0.1 to 0.5 mg/kg) when compared with diets of higher boron intake (1 to 15 mg/kg) have been found to induce biochemical and functional changes often considered detrimental, particularly bone health (growth and maintenance), brain function, and inflammatory response.Nielsen 2009, Nielsen 2009

In humans, boron intake of 1 to 3 mg/day compared with intakes between 0.25 and 0.5 mg/day appear to have beneficial effects on bone and brain health,Nielsen 2008, Nielsen 2009 while boron deprivation studies have shown an effect on markers for inflammatory response.Nielsen 2009

Boron deficiency

While no specific boron deficiency state has been described,Jamison 2003, Nielson 2008 signs of boron deficiency in humans include the followingNielsen 2009: altered macromineral, electrolyte, energy substrate, nitrogen, and oxidative metabolism; changes to erythropoiesis and hematopoiesis; electroencephalogram (EEG) changes suggesting depressed behavioral activation and mental alertness; depressed psychomotor skills; and depressed cognitive processes of attention and memory.

Bone and joint health

Boron is known to influence a variety of metabolic actions. It interacts with calcium, vitamin D, and magnesium, which are all important in bone metabolism.Devirian 2003, Beattie 1993, Meacham 1994 Boron accumulates in bone in concentrations dependent on the amount consumedChapin 1998; bone mineral density has been shown to be related to boron intakeBeattie 1993; calcium appears to be more readily stripped from bones in people with low boron intake; and boron may be particularly effective in protecting bone mass in individuals with vitamin D, magnesium, and potassium deficiency.Nielsen 1009, Schaafsma and 2001, Reid 1993 Boron may also influence the metabolism of other minerals, such as copper, potassium, and phosphorus.Devirian 2003, Jamison 2003, Beattie 1993, Meacham 1995 Boron has also been found to increase estrogen concentrations in postmenopausal womenNielsen 1987 and in healthy men.Naghii 1997 Therefore, it is likely that boron may play a role in bone health through formation or enhancement of steroid hormones preventing calcium loss and consequent bone demineralization, which may explain the epidemiological evidence that boron is essential for healthy bones and joints.Newnham 1994, Palacios 2006

Animal data

Various studies show boron alone is beneficial to bone.Gorustovich 2008, Gorustovich 2008 One study in rats showed that boron deprivation (0.1 mg/kg diet) compared with boron supplementation (3 mg/kg diet) resulted in decreased bone volume fraction and trabecular thickness, and increased trabecular separation and structural model index (a lower level is preferable) promoting bone strength.Nielsen 2006, Nielsen 2009 In another study comparing rats fed boron 0.07 mg/kg compared with 3 mg/kg, boron deprivation decreased bone volume fraction in the alveolus 14 days after tooth extraction.Gorustovich 2008, Gorustovich 2006 Boron deprivation studies showed decreased bone strength in femurs of female ratsNielsen 2004 and pigs.Armstrong 2000, Armstrong 2002

Boron deprivation may not markedly affect calcium and phosphorus concentrations in bone, but rather the concentrations of other minerals (eg, magnesium, potassium, copper, zinc)Nielsen 2004, Nielsen 2007 associated with the formation, differentiation, and activity of osteoblasts and osteoclasts. Mice fed a boron-deficient diet (0.07 mg/kg) for 9 weeks compared with mice supplemented with boron 3 mg/kg exhibited decreased osteoblast surface and increased quiescent bone-forming surface of periodontal alveolar bone.Gorustovich 2008

Various environmental and dietary factors may enhance the effects of boron. Several studies have shown that when animal models are fed marginal amounts of vitamin D, classic signs of vitamin D deficiency related to bone and calcium metabolism are exhibited in boron-deprived animals but not in animals fed nutritional amounts of boron.Hunt 1989, Hegsted 1991, Bai 1996 Similarly, boron has been shown to increase the efficacy of estrogen supplementation in rats, resulting in a beneficial effect on trabecular bone volume fraction, bone growth plate density, and trabecular separation.Sheng 2001 The combination of boron and estrogen versus either alone also markedly improved the apparent absorption of calcium, phosphorus, and magnesium, as well as the retention of calcium and magnesium.Sheng 2001 In this and other studies, boron supplementation alone did not improve any of these variables in the ovarectomized rats.Sheng 2001, Stoecker 2005 A recent study comparing rats and their offspring supplemented with boron 0 to 3 mg/kg and fed either safflower oil or fish oil showed a beneficial effect from boron supplementation on trabecular microarchitecture and cortical bone strength, and that feeding fish oil instead of safflower oil is beneficial to vertebral and cortical bone strength. Boron and fish oil apparently have beneficial effects through different mechanisms that sometimes appear complementary.Sheng 2001

Clinical data

Studies have shown that the concentration of boron in bonesNewnham 1981 and synovial fluidNewnham 1981, Havercroft 1991 of people with rheumatoid arthritis is lower than in people without this disorder.

Surgeons have observed that bones of patients who use boron supplements are much harder to cut than bones of patients who do not.Newnham 1994 It has also been observed that boron supplements apparently accelerate the healing of broken bones.Nielsen 2008

An epidemiologic relationship has also been established between arthritis and low boron intake. In areas of the world where boron intake is 1 mg/day or less, the estimated incidence of arthritis ranges from 20% to 70%, whereas in areas where boron intake is usually 3 to 10 mg/day, the estimated incidence ranges from 0% to 10%.Newnham 1994 Low boron intake may also worsen rheumatoid arthritis and osteoarthritis and decrease the ability to engage in physical exercise that requires a high-energy output.Jamison 2003

A double-blind, placebo-boron supplementation trial in 20 patients with osteoarthritis showed that 50% receiving boron 6 mg/day improved on self-reported measures of joint swelling, restricted movement, and analgesia compared with only 10% in those receiving placebo.Travers 1990

In postmenopausal women, the increases in serum 17beta-estradiol induced by estrogen therapy were higher when consumed with 3.25 mg/day of boron instead of 0.25 mg/day of boron.Nielsen 1992 Dietary boron had no effect in men or women not ingesting estrogen. These findings suggest that boron can enhance and mimic some effects of estrogen ingestion.Nielsen 2004

Boron neutron capture therapy

Boron-based compounds are used in conjunction with radiation therapy to enhance the selective killing of neoplastic cells. Boron neutron capture therapy is based on the ability of the stable isotope 10B to capture neutrons, which leads to a nuclear reaction producing an alpha- and a 7Li-particle, both having high biological effectiveness and a very short range in tissue, thus opening the possibility for a highly selective cancer therapy.Wittig 2008, Hunter 2009 This type of therapy is being examined in clinical trials in resistant and difficult-to-treat cancers.Haselsberger 1994, Kankaanranta 2007, Pisarev 2007, Suzuki 2007, Suzuki 2007, Miyatake 2007

Brain function, cognitive performance, and psychomotor function

Boron may be important in brain function,Penland 1994, Penland 1998 with deprivation impairing cognitive and psychomotor function, resulting in decreased mental alertness and poorer performance at tasks requiring speed and dexterity, attention, and/or short-term memory.Penland 1994, Institute of Medicine 2012

Animal data

Measures of brain electrophysiology and behavior have been shown to be sensitive to boron nutritional inadequacy in animals.Penland 1989, Penland 1993 In a study comparing rats fed 0 versus 3 mcg/g of boron for 75 days, more activity was seen in the lower frequencies than in the higher frequencies on electrocorticograms.Penland 1993

One study found that boron deprivation alters rat behavior and brain mineral composition differently when dietary fat (75 g/kg) was supplied as fish oil (65 g/kg plus 10 g/kg of linoleic acid) instead of safflower oil.Nielsen 2006 Boron-deficient (0.1 mg/kg diet) rats were less active than boron-adequate (3.1 mg/kg diet) rats when fed safflower oil, but when fed fish oil, the activity response to boron deprivation was attenuated.Nielsen 2006

Clinical data

Various studies in healthy older men and women assessed brain EEG activity and response to cognitive and psychomotor performance with dietary manipulation of boron (0.25 vs 3.25 mg per 2,000 kcal/day).Penland 1994, Penland 1989, Penland 1900 All studies provided evidence that relatively short periods of restricted boron intake can affect brain function and cognitive performance in otherwise healthy people.Penland 1994

The most consistent EEG finding seen with low boron intake was a shift toward more activity in the lower frequencies and less activity in the higher, dominant frequencies of the EEG spectrum.Penland 1994 This same effect is often observed in response to nonspecific malnutrition and heavy metal toxicity.Nielsen 2008, Penland 1994 In addition, increased low frequency activity is typical in states of drowsiness and reduced mental alertness and has been associated with poorer performance on vigilance and psychomotor tasks, as well as decreased high-frequency activity related to impaired memory in some conditions.Nielsen 2008, Penland 1994

Effects on psychomotor skills and cognitive processes of attention, perception, and memory were variable.Nielsen 2008, Penland 1994 In the same studies,Penland 1994, Penland 1989, Penland 1990 search-count (a measure of attention) and symbol-count (a measure of encoding skills and short-term memory) consistently showed that boron deprivation impaired response times. However, not all tasks were adversely affected by dietary boron deprivation.

While boron deprivation may have an adverse effect on brain function, there is no evidence that supplementation above normal dietary levels can enhance mental acuity or improve alertness.

Drug design

The structural and electronic aspects of boron and its compounds are creating interest in a new generation of drugs that could possibly interfere with target molecules not readily accessible to carbon-based compounds. Bortezomib (Velcade), a proteasome inhibitor, is indicated for the treatment of hematologic malignancies, and other boron-based drugs are in the pipeline, including AN2690 for the treatment of onychomycosis and antibiotics that might be less likely to trigger resistance.Hunter 2009

Dysmenorrhea

A triple-blind, randomized, placebo-controlled clinical trial conducted in 113 single female university students with primary dysmenorrhea explored the effects of boron supplementation on pain severity and duration. Boron supplementation (300 mg daily for 5 days; equivalent to 10 mg/day boron) was taken through the first 3 days of menstrual flow for 2 consecutive cycles. Over time across the 2 cycles, mean severity (P=0.001) and duration (P=0.032) of pain were significantly lower with boron than in the control group. No major side effects were observed.Nikkhah 2015

Inflammatory or immune response

Other diverse responses reported for low boron intake include effects on membrane integrity and function, impairment of hormone receptors (including decreased insulin sensitivity) and signal transduction functions, and regulation of enzymatic activity.Devirian 2003, Jamison 2003, Nielsen 2009, Hunt 1998 Some of these responses may play a role in inflammatory or immunological regulation and may be secondary to a primary action.

Animal data

There are numerous studies in animals that suggest boron may have a regulatory role in inflammatory or immune response. These include boron-supplemented rats demonstrating reduced swelling and lower circulating concentrations of natural killer and immune cells after injection with an antigen to induce arthritisHunt 1999; delayed onset of adjuvant-induced arthritis in ratsHunt 1999; lower skin-fold thickness response to an intradermal injection of phytohemagglutination in pigsArmstrong 2001; and lower antibody response to injected typhoid antigen in ratsBai 1997; when compared with boron-low or -deficient diets.

A recent study in miceBourgeois 2007 showed boron deprivation downregulated 30 of 31 cytokines or chemokines associated with the inflammatory response 6 days after infection with the nematode H. bakerii. Another studyArmstrong 2003 showed lower serum tumor necrosis factor-alpha and interferon-gamma after lipopolysaccharide injection in pigs fed a marginal boron-deficient diet than in those supplemented with a 5 mg/kg of boron diet.

Clinical data

Boron status in humans has been shown to affect various immunological markers. These include increased white blood cells, increased percentage of polymorphonuclear neutrophils, and decreased percentage of leucocytes in perimenopausal women during the period of boron supplementation.Nielsen 1999 Self-reported improvement in symptoms in patients with osteoarthritis consuming 6 mg/day of boron when compared with placebo,Travers 1990 may be a result of an effect on the inflammatory response.

Low boron intake has been associated with increased risk of prostate cancerCui 2004, 61; higher cytopathological indicators of cervical cancerKorkmaz 2007; some types of breast cancerTouillaud 2005; and lung cancer,Mahabir 2008 possibly due to an immune system effect.

Urolithiasis

One investigator has reported the use of boron supplementation in approximately 30 cases to facilitate dissolution and/or passing of urinary stones with minimal pain. Boron was well tolerated without observation of side effects. Boron was supplemented at 10 mg/day with and without additional antioxidants for 2 to 60 days.Naghii 2012, Naghii 2013, Naghii 2014 In the absence of a control group, it’s difficult to attribute the results to boron.

Vulvovaginitis

Studies show that intravaginal boric acid can treat candidiasis and other vaginal fungal infections, including resistant and chronic infection.Thai 1993, Van Slyke 1981, Swate1974, Guaschino 2001, Jovanovic 1991 One study reported that boric acid used intravaginally cured 92% versus 64% with nystatin 100,000 units for Candida albicans.Van Slyke 1981 For Candida glabrata, intravaginal boric acid successfully treated 65% to 70% of azole-resistant infections.Sobel 2003, Sobel 1997 For Candida krusei, which is rare but resistant to azole antifungal treatment, boric acid appeared to be effective in some cases.Singh 2002

Dosing

Oral dosing

The 1994-96 Continuing Survey of Food Intakes by Individuals indicated that the median boron intakes ranged from a low of about 0.75 mg/day to a high of about 1.35 mg/day.Institute of Medicine 2012 No recommended daily allowance has been established for boron because an essential biological role has not been identified, although the World Health Organization has suggested 1 to 13 mg/dayWHO 1996 as an acceptable safe range for adults. Dietary intake varies. Diets considered high in boron provide about 3.25 mg of boron per 2,000 kcal/day. Diets considered low in boron provide 0.25 mg of boron per 2,000 kcal/day.Penland 1994

Boron has been studied at a wide range of doses. Daily dosages of 2.5 to 10 mg of boron have been administered for osteoarthritisNewnham 1994 and strength conditioning.Green 1994, Ferrando 1993 Individuals consuming 0.25 mg/day respond positively to boron supplementation of 1 mg/day.Jamison 2003 A single dose of 102.6 mg of sodium tetraborate was studied for its effects on factor VIIa.Wallace 2002

The tolerable upper intake level (UL) for boron, the maximum dose at which no harmful effects would be expected, isNielsen 2009, Institute of Medicine 2012:

For adults 19 years and older, including pregnant or breast-feeding women

20 mg/day

For adolescents 14 to 18 years of age, including pregnant or breast-feeding adolescents

17 mg/day

For children 9 to 13 years of age

11 mg/day

For children 4 to 8 years of age

6 mg/day

For children 1 to 3 years of age

3 mg/day

For infants younger than 1 year

a UL has not been established.

A 2009 review recommended that patients on parenteral nutrition receive 1 mg/day because it is unlikely that this amount is being delivered in current parenteral solutions.Nielsen 2009

Vaginal dosing

For treatment of vulvovaginal candidiasis, boric acid 600 mg once or twice daily for 2 weeks has been used.Van Slyke 1981, Swate 1974, Guaschino 2001, Jovanovic 1991, Sobel 2003, Sobel 1997 For prevention of recurring vulvovaginal candidiasis, boric acid 600 mg twice weekly has been used.Jovanovic 1991, Sobel 1997

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking, but when boron is used orally in doses below UL, it is likely to be safe.Institute of Medicine 2012 Boric acid should not be used in pregnancy. Intravaginal boric acid has been associated with birth defects if used during the first 4 months of pregnancy.Thai 1993, Acs 2006, MedlinePlus 2015

Interactions

Boron supplementation in patients with estrogen-sensitive conditions (eg, breast cancer, uterine cancer, ovarian cancer, endometriosis, uterine fibroids) should be avoided, and it should be used cautiously with concomitant estrogens because it may increase the levels or enhance the activity of estrogen.MedlinePlus 2015

There are no known interactions with other drugs or foodsMedlinePlus 2015; however, supplementation may result in changes in plasma levels of phosphorous and magnesium.Meacham 1994

Adverse Reactions

Clinical information concerning the adverse effects of boron is limited. Recommendations regarding the oral dose below which adverse reactions are unlikely range from 10Naghii 1997 to 20 mg/day.Institute of Medicine 2012

Although compounds containing boron are used medicinally, they are potentially toxic if ingested or absorbed through nonintact skin. Long-term use of boric acid orally 1 g/day or boric tartrate 15 g/day can cause dermatitis, alopecia, anorexia, lethargy, and indigestion.Institute of Medicine 2012 Boric acid has been well tolerated intravaginallyRein 1981 and does not appear to result in systemic absorption.Thai 1993 Vulvovaginal burning has been reported. Dyspareunia may occur in males if intercourse occurs shortly after vaginal treatment.Van Kessel 2003

Toxicology

Boric acid and borates can be toxic when ingested. The minimum lethal dose of boric acid is 640 mg/kg/day, with the potential lethal dose reported to be 15 to 20 g/day for adults and 3 to 6 g/day for infants.Institute of Medicine 2012 Animal studies have shown that high doses of borax and boric acid may adversely affect male fertility; however, this has not been observed in humans.Institute of Medicine 2012, Scialli 2010

Boric acid solutions should not be used on broken skin or on severely irritated or inflamed mucous membranes in order to prevent possible toxicity via absorption.

Boron should be used with caution in patents with impaired kidney function because it is primarily excreted renally.Institute of Medicine 2012, Usuda 1996

Fatalities have been reported because of confusion between boric acid and similar-looking powders (ie, baking soda, dextrose). Stringent controls should be maintained in hospitals, nursing homes, and other public facilities to prevent possible intoxications due to errant use of boron-containing products.

There is no effective antidote to boron poisoning, and treatment is symptomatic and supportive. Symptoms of toxicity include headache, irritation and sloughing of skin, GI upset including diarrhea and vomiting, restlessness and irritability, somnolence, weakness, tremors, kidney and liver damage, convulsions, coma, or death.

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