The Physiological Role of Boron on Health – Nov 2018

Biological Trace Element Research, November 2018, Volume 186, Issue 1, pp 31–51
Haseeb Khaliq Zhong JumingPeng Ke-Mei

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Boron is an essential mineral that plays an important role in several biological processes. Boron is required for growth of plants, animals, and humans. There are increasing evidences of this nutrient showing a variety of pleiotropic effects, ranging from anti-inflammatory and antioxidant effects to the modulation of different body systems. In the past few years, the trials showed disease-related polymorphisms of boron in different species, which has drawn attention of scientists to the significance of boron to health. Low boron profile has been related with poor immune function, increased risk of mortality, osteoporosis, and cognitive deterioration. High boron status revealed injury to cell and toxicity in different animals and humans. Some studies have shown some benefits of higher boron status, but findings have been generally mixed, which perhaps accentuates the fact that dietary intake will benefit only if supplemental amount is appropriate. The health benefits of boron are numerous in animals and humans; for instance, it affects the growth at safe intake. Central nervous system shows improvement and immune organs exhibit enhanced immunity with boron supplementation. Hepatic metabolism also shows positive changes in response to dietary boron intake. Furthermore, animals and human fed diets supplemented with boron reveal improved bone density and other benefits including embryonic development, wound healing, and cancer therapy. It has also been reported that boron affects the metabolism of several enzymes and minerals. In the background of these health benefits, low or high boron status is giving cause for concern. Additionally, researches are needed to further elucidate the mechanisms of boron effects, and determine the requirements in different species.

Table of Contents

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Mechanism of Action for the Bioactivity of Boron

A plausible mechanism of boron action may be clarified by the boron biochemistry. Boric acid along with hydroxyl groups of organic compounds forms ester complexes. This characteristic mostly results in the complex formation with numerous biologically essential sugars [229]. These sugars comprise ribose, which is a part of adenosine. Recent studies suggest that the versatile favorable effects of boron happen through distressing the presence of biomolecules containing adenosine. The most important biomolecules that have more boron affinities include adenosine phosphates (ADP) and S- adenosylmethionine (SAM-e) in animal tissues [229]. ADP are occurred in all animal cells and serve as signal nucleotides in neuronal response. SAM-e is one of the utmost often used enzyme substrate in the body [230]. About 95% of SAM-e is involved in methylation responses, which affect the RNA, DNA, phospholipids, proteins, and hormonal activities. These methylation reactions end in the formation of SAM-e, which further hydrolyzed into homocysteine. The boron- deficient rats showed increased plasma homocysteine and decreased SAM-e which support the hypothesis that boron bioactivity is through an effect on SAM-e formation [231]. Furthermore, depleted SAM-e has been found in disorders like osteoporosis, arthritis, diabetes, and urolithiasis which are affected by nutritional intake of boron [208].
The hypothesis is further supported by bacterium quorum sensing signal molecule, AI-2, a furanosyl borate diester synthesized from SAM-e. AI-2 plays an important role and incorporates boron. AI-2 signaling is produced by the reaction of 1- deoxy-3-dehydro-D-ribulose, which is raised enzymatically, with boric acid [31]. Bacterium quorum sensing is the cell- to-cell communication accomplished through the exchange of extracellular signaling molecules. Furthermore, boron binds strongly to the oxidized form ofNAD+ [229], thus influencing those reactions in which it is participating. One of the roles of NAD+ is binding on plasma membrane with CD38 receptor which is ADP ribosyl cyclase and converting NAD+ into cyclic ADP-ribose sugar. This cyclic ADP binds to ryanodine receptor in the endoplasmic reticulum and encourages calcium ion release [56]. Boron is a reversible inhibitor of cyclic ADP- ribose and its concentration decreased calcium ion release from ryanodine receptor [56]. Therefore, it can be hypothesized that bioactivity of boron is through binding cyclic ADP ribose and NAD+ and inhibiting calcium ion release, which is helpful in many processes including bone formation, brain activity, liver function, and immune response. Studies with plants proposed another possible mechanism of action for boron bioactivity. Boron might also showed bioactivity through forming ester borate complexes with glycoproteins, glyco- lipids, and phosphoinositides, in cellular membranes. These ester complexes may act as redox modifiers and calcium chelators [63] that affect the membrane function and integrity [232]. This modifying action could affect the transduction of regulatory or signaling ions across the membranes. The effects of this mechanism in animals and human are still to be determined.

Interaction of Boron with Other Nutrients

The numerous biological effects of boron which are described above may be associated with its interaction with different minerals. For instance, it binds with diverse organic compounds to affect various biological functions [78]. Several studies have demonstrated that chicks deficient in vitamin D show increased levels of plasma glucose on exposure to boron [204, 205]. Furthermore, chicks deficient in vitamin D show higher plasma concentrations of pyruvate and triglycerides (TG); however, administration of dietary boron alleviated these effects [206]. Boron deficiency in rats leads to vitamin D deficiency and ultimately raised plasma pyruvate and reduced plasma TG concentrations [207]. Conversely, no such effects had been reported, when the diet had enough levels of boron [206, 65]. Boron deficiency also promotes hyperinsulinemia [207], when dietary levels of either vitamin D or Mg are altered in chicks and rats [134], and influences on growth. A study was conducted to determine the dietary levels of Mg and Ca that are required for effective interaction with boron, and it was reported that boron was necessary for growth, and Mg deficiency might represent a source of stress in boron metabolism [208].
Furthermore, boron supplementation reduced the abnormalities level induced by Mg deficiency in chicks. Boron supplementation also enhanced plasma concentration of Ca and Mg, which ultimately lead to inhibition of calcification and other complications [209]. Because of this ability, it has been reported that boron is used to treat and prevent hypomagnesemia, hypocalcemia (milk fever), and fatty liver in lactating dairy cows [8]. It was also reported that low calcium diet in lambs caused oxidative stress, reduced immune response, less growth rate, and alteration in kidney/liver tissues, but supplementation of boron to this diet restored normal functions along with ameliorated effects on morphology of organs [210]. In another study, when boron was supplemented in the diet of chickens, Ca and P deficiency was reduced and growth was enhanced [65]. Furthermore, while boron was supplemented in the diets of rats with severe K deficiency, a supportive effect was evident through the maintenance of body fat and enhancement of glycogen deposition in the liver [211, 212]. It has previously been reported that boron has an antidotal effect in the control of fluorosis in buffalo due to its interaction with various minerals. The high intake of fluoride in the body caused serious complications in the body as it caused an improvement in the activity of ALP and phosphorus, while causing the decrease in calcium levels. However, boron supplementation caused ameliorated effect on serum mineral profile against fluoride toxicity [213]. Recently, it was demonstrated that supplemental boron can be used for the cure of acute cadmium toxicity. The results showed that boron reversed the toxicity induced by cadmium and protect the liver and kidney from severe damage [214]. Boron may also alter biological systems because of its affinity for cis- hydroxyl groups of the cell membrane and interfere with manganese-dependent enzymatic reactions [6, 215].

Conclusions

Recent findings have reinforced the significance to health of adequate boron status. The effects of boron are multiple and versatile, demanding further studies to elevate the benefits and lessen the hazards of this influential trace mineral. When administered at an effective dose, boron shows remarkable properties, and its nutritional value cannot be underestimated.
Experimental boron administration in animals and humans has resulted in marked improvement in

• immunity,
• anti- oxidative effects,
• growth, and
• embryonic development.

Boron also facilitates improvements in

• brain function,
• hepatic development,
• osteoporosis,
• cancer therapy, and
• wound healing.

Conversely, high dose of boron showed opposite effects; that is why usage of boron is still limited on commercial scale. Although numerous trials on boron have been executed over the previous decade, additional data is required to illuminate its mechanism of actions. The new methods should also be developed to estimate the requirement of boron in each species, which may have encouraged the therapeutic aspects and field applications.