Sugar–borates (SBs) are mono- or di-sugar–borate esters (SBEs) comprised of one or two monosaccharide molecules linked to a boron (B) atom. SBEs occur naturally in commonly consumed herbs, vegetables, fruits, seeds, and nuts and, other than greatly varying levels of B found in local drinking water, are the primary natural dietary sources of B-containing molecules in humans. To date, the most studied SBE is calcium fructoborate (CaFB). CaFB represents an important example of how organic B-containing molecules are significantly distinct from their inorganic counterparts. During these past two decades, CaFB has been researched for its physical and biochemical characteristics, safety, and clinical outcomes. Results of these researches are presented and discussed herein. CaFB has been characterized using Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), high-performance thin-layer chromatography (HPTLC), nuclear magnetic resonance (NMR), liquid chromatography–multistage accurate mass spectrometry (LC-MSn), X-ray diffraction (XRD), Raman spectroscopy, and inductively coupled plasma (ICP) in non-biological and biological specimens. Potential health benefits of CaFB have been clinically investigated in pilot and efficacy studies demonstrating (i) significant reductions in knee discomfort and improved flexibility within 7, 14, and 90 days and (ii) significant effect on blood levels of inflammatory, cardiovascular, and other biomarkers. These studies support the use of CaFB as a dietary supplement for the management of joint discomfort. CaFB is presented here in order to illustrate how physiological benefits are imparted by distinct organic boron-containing molecules rather than solely by the element B itself. Considering recent National Health and Nutrition Examination Survey (NHANES) data reporting increases in age-related joint pain and an increasing elderly demographic, SBEs offer potential for safe, natural, and effective management of joint discomfort and improved mobility in human and animal health applications. Several of these studies may also open new opportunities for use of SBEs for health benefits beyond joint health.

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Calcium fructoborate (CFB) has been reported as supporting healthy inflammatory response. In this study, we assess the effects of CFB on blood parameters and proinflammatory cytokines in healthy subjects. This was a randomized, double-blinded, placebo-controlled trial. Participants received placebo or CFB at a dose of 112 mg/day (CFB-1) or 56 mg/day (CFB-2) for 30 days. Glucose, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), C-reactive protein (CRP), homocysteine, interleukin 1 beta (IL-1β), IL-6, and monocyte chemoattractant protein-1 (MCP-1) were determined before and after supplementation. CFB-1 showed a reduction in blood levels of CRP by 31.3 % compared to baseline. CFB-1 and CFB-2 reduced LDL levels by 9.8 and 9.4 %, respectively. CFB-1 decreased blood homocysteine by 5.5 % compared with baseline, whereas CFB-2 did not have a significant effect. Blood levels of TG were reduced by 9.1 and 8.8 % for CFB-1 and CFB-2, respectively. Use of both CFB-1 and CFB-2 resulted in significantly reduced IL-6 levels, when compared within and between groups. IL-1β was reduced by 29.2 % in the CFB-1 group. Finally, CFB-1 and CFB-2 reduced MCP-1 by 31 and 26 %, respectively. Our data indicate that 30-day supplementation with 112 mg/day CFB (CFB-1) resulted in a significant reduction of LDL, TG, TC, IL-1β, IL-6, MCP-1, and CRP. HDL levels were increased, when compared to baseline and placebo. These results suggest that CFB might provide beneficial support to healthy cardiovascular systems by positively affecting these blood markers (ClinicalTrials.gov, ISRCTN90543844; May 24, 2012 (http://www.controlled-trials.com/ISRCTN90543844)).

Calcium fructoborate (CF), a natural sugar-borate ester found in fresh fruits and vegetables, is a source of soluble boron. CF contains three forms of borate (diester, monoester, and boric acid) and all are biologically active, both at the intracellular (as free boric acid) and extracellular level (as fructose-borate diester and monoester). At the cellular and molecular level, CF is superior to the boric acid/borate, exhibiting a complex “protective” effect against inflammatory response. CF is commercially available in the USA as a “nature-identical” complex, an active compound for dietary supplements. It provides effective and safe support against the discomfort and lack of flexibility associated with osteoarticular conditions (arthritis and joint degeneration), and improves Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and McGill indexes. In addition, orally administered CF is effective in ameliorating symptoms of physiological response to stress, including inflammation of the mucous membranes, discomfort associated with osteoarthritis disorders, and bone loss, and also for supporting cardiovascular health. Clinical studies have exhibited the ability of CF to significantly modulate molecular markers associated with inflammatory mechanisms, mainly on the elevated serum levels of C-reactive protein (CRP).

Boron (B) is considered a prebiotic chemical element with a role in both the origin and evolution of life, as well as an essential micronutrient for some bacteria, plants, fungi, and algae. B has beneficial effects on the biological functions of humans and animals, such as reproduction, growth, calcium metabolism, bone formation, energy metabolism, immunity, and brain function. Naturally organic B (NOB) species may become promising novel prebiotic candidates. NOB-containing compounds have been shown to be essential for the symbiosis between organisms from different kingdoms. New insights into the key role of NOB species in the symbiosis between human/animal hosts and their microbiota will influence the use of natural B-based colon-targeting nutraceuticals. The mechanism of action (MoA) of NOB species is related to the B signaling molecule (autoinducer-2-borate (AI-2B)) as well as the fortification of the colonic mucus gel layer with NOB species from B-rich prebiotic diets. Both the microbiota and the colonic mucus gel layer can become NOB targets. This paper reviews the evidence supporting the essentiality of the NOB species in the symbiosis between the microbiota and the human/animal hosts, with the stated aim of highlighting the MoA and targets of these species.

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Firmly attached to different living or non-living, solid or fluid surfaces rich in nutrients and moisture, microbial biofilm is a matter of great interest due to its major importance for the healthcare community. Depending on common strategies such as mutual protection and hibernation (quiescent bacteria), the resistance, survival and virulence of microbial communities have large implications for human pathology, clinical environment and biomedical devices. The microbial biofilm is continuously changing, stimulating inflammation, increasing vascular permeability and preventing the action of macrophages. About 80% of human infections affecting the gastrointestinal, genitourinary and respiratory systems, oral mucosa and teeth, eyes, middle ear and skin are caused by biofilm-associated microorganisms. Therefore, the search for modern strategies is even more important as microbial biofilms resistant to conventional antibiotics, antiseptics and disinfectants are involved in the frequent treatment failures of some chronic inflammatory diseases and wounds. Natural products containing secondary metabolites, such as aromatic compounds, sulphurated derivatives, terpenoids (essential oils) and alkaloids as quorum-sensing inhibitors and biofilm disruptors, are promising alternatives for the prophylaxis and treatment of chronic infections. Surface modification of medical devices with non-polar functionalized nanoparticles stabilizes the natural compounds antibiofilm activity and inhibits microbial adhesion and biofilm formation and growth for a longer period of time. In this regard, an interdisciplinary approach is needed due to the large number of natural derivatives alone or in combination with biocompatible and biodegradable micro-/ nano-engineered materials.

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