Chapter 70 Boron*
Introduction
Boron is a ubiquitous constituent of the environment, typically occurring in nature as inorganic borates. In human tissues, boron is found as the borate anion and boric acid, predominantly the latter form, with a concentration primarily reflecting dietary intake.1,2 In trace amounts boron is essential for the growth of many plants, and although it has yet to be recognized as an essential nutrient for humans, data from animal and human studies continue to suggest that boron is important for many life processes. This includes embryogenesis; bone growth and maintenance; immune function; regulation of inflammation; psychomotor skill; mineral metabolism; brain function and performance; and prevention of osteoporosis, osteoarthritis, and prostate, lung, and cervical cancer.3 It also has been shown to affect the metabolism or action of many biological compounds, including glucose, S-adenosylmethionine, amino acids, triglycerides, macrominerals, and a number of hormones, including vitamin D, insulin, testosterone, and estrogen.4,5
Sources
Because boron in plants depends on the availability of boron in the soil, the same food crop can vary greatly in boron content depending on where and how it is grown. In general, soils exposed to high degrees of precipitation have decreased levels of boron.6 Heavy rainfall leaches the highly soluble boric acid from the soil, whereas in more arid regions, evaporation of groundwater results in higher concentrations of boron solutes. Food processing results in additional loss of boron, and the use of superphosphate and potash fertilizers reduces its uptake by plants.7,8 Foods of plant origin, such as leafy vegetables, noncitrus fruits (apples), nuts, legumes (peanut butter), avocados, and sea vegetables are considered the best sources of boron.1,9 Wine has also been shown to contribute appreciable amounts of boron to the diet, and water intake may also be a significant source of total intake.10 A diet containing an abundance of these items would provide 2 to 6 mg/day of boron.9,11
Daily intake of boron depends on several variables. Concentration of boron in water varies considerably according to geographic source. In some areas boron in drinking water and water-based beverages may account for most of the total dietary boron intake. Individual food preference greatly influences daily intake of boron. Fruits, vegetables, tubers, and legumes have higher concentrations of boron than do cereal grains or animal tissues. For adults and seniors, though, the largest source of boron turns out to be instant regular coffee.12 Given the poor dietary intake of produce in the United States, the top two boron contributors to adult boron intake, coffee and milk, are actually deficient in this nutrient (Table 70-1)13 compared with other more nutritious foods. Nevertheless, these make up 12% of the total boron intake by virtue of the volume consumed.13 Boron has also been determined to be a notable contaminant or major ingredient of many personal care products, and it (boric acid) is occasionally used as a food preservative.14
FOOD | BORON (mg/mL) |
---|---|
Coffee, from ground beans | 0.029 |
Milk, whole | 0.018 |
Apples, raw | 0.36 |
Beans, refried | 0.4 |
Potatoes, from French fries | 0.11 |
Orange juice | 0.072 |
Peanut butter | 1.145 |
Wine | 0.61 |
Apple juice | 0.18 |
Cola | 0.013 |
Data from Rainey CJ, Nyquist LA, Christensen RE, et al. Daily boron intake from the American diet. J Am Diet Assoc. 1999;99:335-340.
In Sydney, Australia, 32 subjects aged 20 to 53 years old were assessed over a 7-day period for their dietary intake of boron. The average boron intake in male and female subjects was found to be 2.28 ± 1.3 and 2.16 ± 1.1 mg/day, respectively.10 The boron content of selected Australian foods has been found to correlate with values in Finnish and U.S. Food and Drug Administration tables and is presented in Table 70-2 (note, however, the large variations between countries and even regions of a country).10 Regional differences are certainly important. An analysis of nearly 300 foods that are commonly consumed in Korea found considerable discrepancies with values reported elsewhere. For example, the boron content in Korean apples was found to be one-twelfth that found in German apples. The foods found to be richest in boron (in micrograms/100 g) included buckwheat flour (828), soybeans (1642), mung beans (818), almonds (917), cocoa (2026), coffee powder (approximately 1530), and oolong and green tea powder (1274 and 1316, respectively).15
FOOD | BORON (mg/100 g) |
---|---|
Almonds | 2.82 |
Apples (red) | 0.32 |
Apricots (dried) | 2.11 |
Avocados | 2.06 |
Bananas | 0.16 |
Beans (red kidney) | 1.4 |
Bran (wheat) | 0.32 |
Brazil nuts | 1.72 |
Broccoli | 0.31 |
Carrots | 0.3 |
Cashews (raw) | 1.15 |
Celery | 0.5 |
Chickpeas | 0.71 |
Dates | 1.08 |
Grapes (red) | 0.5 |
Hazelnuts | 2.77 |
Honey | 0.5 |
Lentils | 0.74 |
Olives | 0.35 |
Onions | 0.2 |
Oranges | 0.25 |
Peaches | 0.52 |
Peanut butter | 1.92 |
Pears | 0.32 |
Potatoes | 0.18 |
Prunes | 1.18 |
Raisins | 4.51 |
Walnuts | 1.63 |
Wine (Shiraz Cabernet) | 0.86 |
Metabolism
Chemical Properties
Elemental boron was first isolated in 1808. It is the first member (atomic number 5) of the metalloid or semiconductor family of elements, including silicon and germanium, and is the only nonmetal of the group IIIA elements. Like carbon, boron has a tendency to form double bonds and macromolecules.16 Boron, as boric acid, acts as a Lewis acid, accepting hydroxyl (OH−) ions and leaving an excess of protons.17 Because boron complexes with organic compounds containing hydroxyl groups, it interacts with sugars and polysaccharides, adenosine-5-phosphate, pyridoxine, riboflavin, dehydroascorbic acid, and pyridine nucleotides.18 Given boron’s affinity for hydroxyl groups, it is possible that it interacts with glycoproteins and glycolipids found in cellular membranes. Animal studies have supported a role for boron in maintaining cellular membrane structure and function, with boron deprivation causing pathologic changes in both zebrafish and frogs.19 Dietary magnesium and essential fatty acids, both of which are involved in cell membrane function, also influence the response to boron deprivation, lending further support for a role for boron. For example, in an animal-based study, boron deprivation was found to alter animal behavior in ways that were modifiable by varying the composition of dietary fatty acids, and vice versa, possibly by altering the fluidity of cellular membranes.20
Biochemistry
Boron in food, sodium borate, and boric acid are well absorbed from the digestive tract.21 However, homeostatic mechanisms for maintaining serum levels of boron exist, with urinary levels mirroring intake.8 A boron transporter has been identified (NaBC1), and dietary supplementation of boron has been shown to alter its genetic expression.4,22 Compounds of boron are also absorbed through damaged skin and mucous membranes; however, they do not readily penetrate intact skin.23
No accumulation of boron has been observed in soft tissues of animals fed long-term low doses of boron; however, in acute poisoning incidents, the amount of boric acid in brain and liver tissue has been reported to be as high as 2000 ppm. Within a few days of consumption of large amounts of boron, levels in blood and most soft tissues quickly reach a plateau.24 Tissue homeostasis is maintained by the rapid elimination of excess boron, primarily in the urine, with bile, sweat, and breath also contributing as routes of elimination.18
Evidence suggests that supplemental boron does accumulate in bone; however, cessation of exposure to dietary boron results in a rapid drop in bone boron levels. The half-life of boric acid in animals is estimated at about 1 day.24
Biological Functions
Boron contributes to living systems by acting indirectly as a proton donor and exerting an influence on cell membrane structure and function.25 Although the absolute essentiality of boron for plants as well as two animal species (zebrafish and frogs) is well documented, studies to date have not shown it to be unequivocally essential for other species or humans. However, boron supplementation has been shown to affect certain aspects of animal physiologic function. In general, supplemental dietary boron has its most marked effects when the diet is deficient in known nutrients.26
Recent animal-based data suggests boron may in some way affect the utilization or production of S-adenosylmethionine, which in turn influences homocysteine metabolism, as well as other molecules involved in cellular signaling and differentiation. Rats deprived of boron had increases in plasma cysteine and homocysteine as well as decreases in hepatic S-adenosylmethionine and the related compounds S-adenosylhomocysteine and spermidine. It is possible that many of boron’s biological effects are mediated through this mechanism, because S-adenosylmethionione is involved in many methylation reactions, including DNA methylation, as well as methylation of other neurotransmitters, phospholipids, and signaling molecules, and is also used frequently as an enzyme substrate.27
Evidence suggests that boron might also have an effect on decreasing fasting serum glucose concentrations in postmenopausal women.28
Embryo Maturation
Research has shown that boron is an important player in the early stages of life.3 Boron deficiency negatively affects reproductive ability, as well as embryo development in both the African clawed frog (Xenopus laevis) and the zebrafish. Experimentation with Xenopus noted that dietary boron deprivation elicited necrotic egg increases combined with a high frequency of abnormal gastrulation, causing adverse effects during gametogenesis, gamete maturation, embryonic development, and larval maturation.19 In the zebrafish model, 45% of boron-deprived embryos died during the early postfertilization period. Conversely, only 2% of boron-supplemented embryos died. Other studies with rats and mice corroborated that low boron status might affect reproduction in mammals, although conclusions from these studies were not as clear.
Life Span
Boron in an animal model has been shown to affect life span, although the process is undefined. Extremes in dietary boron, both a deficiency and an excess, appear to affect the median life span of Drosophila. Adding excess during the adult stage decreased life span by as much as 69%, whereas supplementing the diet with low levels of boron increased life span by 9.5%.29 No research exists for other species.
Brain Function and Performance
Although limited data exist for boron’s influence on brain function, existing research is “among the most supportive in demonstrating that boron is a beneficial bioactive element for humans.”30 Brain electrophysiology and cognitive performance were assessed in response to dietary manipulation of boron (approximately 0.25 versus approximately 3.25 mg boron/2000 kcal/day) in three studies with healthy older men and women. A low boron intake was shown to result in a decrease in the proportion of power in the α-band and an increase in the proportion of power in the δ-band, effects similar to those induced by heavy metals and nonspecific malnutrition, as well as mental drowsiness and reduced alertness. Other changes in left–right symmetry and brain wave coherence were noted in various sites, indicating an influence on brain function. When contrasted with the high boron intake, low dietary boron resulted in significantly poorer performance (P <0.05) on tasks emphasizing manual dexterity, eye–hand coordination, attention, perception, encoding, and short- and long-term memory. Collectively, the data from these studies indicate that boron may play a role in human brain function, alertness, and cognitive performance.31
Interestingly, as mentioned previously, essential fatty acid composition may interact with boron status to influence brain function. A number of biomarkers for low activity were observed in boron-deficient rats when given safflower oil, but fish oil negated these deficits.20
Hematologic
Boron supplementation to human subjects who had previously followed a dietary regimen deficient in boron increased blood hemoglobin concentrations, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. It lowered hematocrit, red cell count, and platelet count.32 As discussed in the “Toxicology” section, boron may inhibit the enzyme δ-aminolevulinic acid dehydratase.
Hepatoprotection
Studies of fulminate hepatic failure in Wistar rat models showed boron pretreatment significantly reduced lipid peroxidation, as well as decreased serum liver enzymes in these animals. Boron pretreatment also increased the peroxide-metabolizing enzymes’ levels of glutathione peroxidase and catalase, as well as glutathione itself.33,34
Mineral Metabolism
Boron also affects mineral metabolism as well as related hormones in human subjects. In the first nutritional study with humans involving boron,23 postmenopausal women first were fed a diet that provided 0.25 mg boron/2000 kcal for 119 days and then were fed the same diet with a boron supplement of 3 mg boron/day for 48 days. The boron supplementation reduced the urinary excretion of calcium and magnesium and elevated the serum concentrations of 17 β-estradiol and testosterone.9
In a study designed to determine the effects of boron supplementation on blood and urinary minerals in athletic subjects on Western diets, findings suggested that boron supplementation modestly affected mineral status.35
Deficiency Signs and Symptoms
Information on boron deficiency is limited, especially in humans. It is thought that insufficient intake of boron becomes obvious only when the body is stressed in a manner that enhances the need for it. When the diets of animals and humans are manipulated to cause functional deficiencies in nutrients such as calcium, magnesium, vitamin D, essential fatty acids, and methionine, a large number of responses to dietary boron occur.36 Evidence suggests that more than 21 days on a boron-deficient diet are required to demonstrate detectable effects in humans.37 The variables that are changed due to a boron-deficient diet abruptly improve about 8 days after boron supplementation is introduced.9 Evidence indicates that hemodialysis results in an excessive decrease in serum boron compared with controls.38 Although blood urea is by no means nitrogen pathognomonic for a boron deficiency, it has been found to be slightly elevated during boron depletion.39
Nutrient Interactions
Vitamin D
Considerable evidence indicates that dietary boron alleviates perturbations in mineral metabolism that are characteristic of vitamin D3 deficiency.40 In one study, chicks fed a diet inadequate in vitamin D exhibited decreased food consumption and plasma calcium concentrations and increased plasma concentrations of glucose, β-hydroxybutyrate, triglycerides, triiodothyronine, cholesterol, and alkaline phosphatase activity after 26 days. Supplemental boron returned plasma glucose and triglycerides to concentrations exhibited by chicks fed a diet adequate in vitamin D.41
In rachitic chicks, boron elevated the numbers of osteoclasts and alleviated distortion of the marrow sprouts of the proximal tibial epiphysial plate, a distortion characteristic of vitamin D3 deficiency.40,42 Higher apparent balance values of calcium, magnesium, and phosphorus have been observed for rats fed a vitamin D-deprived diet if the diet was supplemented with boron.26
After supplementation with 3.25 mg boron daily, plasma levels of vitamin D2 increased in men older than age 45 and postmenopausal women on low magnesium and copper diets.43 In a very small human study (n = 8), healthy male volunteers were given 10 mg boron per day for 1 week, resulting in a nonsignificant 7% rise in vitamin D levels.5 Inhibition of 24-hydroxylase, the enzyme that catabolizes vitamin D, has been speculated to be the possible mechanism of action, although this has not been demonstrated.44