Forrest Harold Nielsen

Based on a significant amount of evidence from in vitro, animal, and human experiments, the basic aspect of the mechanism of action of nutritional, pharmacological, and toxicologic inorganic boron is the formation of boron esters with biomolecules that have vicinal cis-diols. The formation of boron esters results in the modulation of the bioactivity of biomolecules, especially those with the ribose moiety, that regulate gene expression, inflammation, oxidation/reduction, membrane function, hormone activity, and signaling. The nutritional and pharmacological modulation has been found to have benefits under conditions with impaired bone formation and maintenance, cognitive function, psychomotor skills, cancer risk, cardiovascular disease, diabetes, immune function, inflammatory symptoms in osteoarthritis and dental disease, embryo development, and aging. Because there is evidence that impairments in these functions occur in animals and humans fed boron-deprived diets, the identification of a mechanism of action supports the concept that boron is a nutrient needed for optimal health and well-being.

Research findings are presented on the nutritional importance of aluminum, arsenic, boron, chromium, copper, iron, lead, magnesium, manganese, nickel, selenium, silicon, tin, vanadium, and zinc. This include findings from animal studies revealing beneficial effects of nutritional or ultra trace amounts of dietary arsenic, nickel, and silicon; showing the importance of zinc for bone health; initiating the study of boron as a possible essential nutrient; the likelihood that chromium and vanadium are beneficial in only pharmacological or supra nutritional amounts, and refuting the claims of essentiality for aluminum, lead and tin. Also, findings from human depletion/repletion experiments are presented showing the induction of boron deprivation signs that are alleviated by nutritional amounts of boron; providing evidence that a low boron status is prevalent in individuals consuming a Western diet; indicating a possible mechanism for the beneficial effects of boron; showing that zinc deficiency increases the need for copper; confirming that high dietary zinc exacerbates signs of copper deficiency; showing magnesium is prevalent in older individuals consuming a Western diet; presenting balance data to give an evidence based reason for updating the magnesium dietary reference intakes; evaluating various methods for magnesium status assessment; providing evidence that magnesium deficiency contributes to the risk of cardiovascular disease; and providing impetus for magnesium being declared an element of nutritional concern.

In the past 20 years, a large number of epidemiological studies, randomized controlled trials, and meta-analyses have found an inverse relationship between magnesium intake or serum magnesium and cardiovascular disease, indicating that low magnesium status is associated with hypertension, coronary artery calcification, stroke, ischemic heart disease, atrial fibrillation, heart failure, and cardiac mortality. Controlled metabolic unit human depletion–repletion experiments found that a mild or moderate magnesium deficiency can cause physiological and metabolic changes that respond to magnesium supplementation, which indicates that these types of deficiencies or chronic latent magnesium deficiency are contributing factors to the occurrence and severity of cardiovascular disease. Mechanisms through which a mild or moderate magnesium deficiency can contribute to this risk include inflammatory stress, oxidative stress, dyslipidemia and deranged lipid metabolism, endothelial dysfunction, and dysregulation of cellular ion channels, transporters, and signaling. Based on USA official DRIs or on suggested modified DRIs based on body weight, a large number of individuals routinely consume less magnesium than the EAR. This especially occurs in populations that do not consume recommended amounts of whole grains, pulses, and green vegetables. Thus, inadequate magnesium status contributing to cardiovascular disease is widespread, making magnesium a nutrient of public health concern.

An environmentally compatible and less costly (greener) analytical method for the digestion of bone meal samples using microwave-assisted dilute nitric acid (HNO₃) was developed and optimized. The method, employing a mixture of 1 mL concentrated HNO₃ and 4 mL of deionized water, offered a comparable performance to the conventional method using 5 mL of concentrated HNO₃. The accuracy of the method was validated by using certified reference material NIST 1486 (Bone Meal); percentage recoveries were within ±15% for all eight certified elements. Statistical analysis revealed no significant differences (p > 0.05) in percentage recoveries between the green and conventional methods for all elements except calcium. The greenness of the developed method was evaluated by using the analytical Eco-Scale, achieving a score of 87, categorizing it as an “excellent green analysis” method. This research highlights the potential for adopting greener practices in trace element analysis that reduce the environmental impact and safety risks associated with concentrated acids.

In the past 20 years, a large number of epidemiological studies, randomized controlled trials, and meta-analyses have found an inverse relationship between magnesium intake or serum magnesium and cardiovascular disease indicating that a low magnesium status was associated with hypertension, coronary artery calcification, stroke, ischemic heart disease, atrial fibrillation, heart failure, and cardiac mortality. Controlled metabolic unit human depletion-repletion experiments found that a mild or moderate magnesium deficiency can cause physiological and metabolic changes that respond to magnesium supplementation, which indicates these types of deficiency or chronic latent magnesium deficiency are contributing factor to the occurrence and severity of cardiovascular disease. Mechanisms through which a mild or moderate magnesium deficiency can contribute to this risk include inflammatory stress, oxidative stress, dyslipidemia and deranged lipid metabolism, endothelial dysfunction, and dysregulation of cellular ion channels, transporters, and signaling. Based on USA official DRIs or on suggested modified DRIs based on body weight, a large number of individuals routinely consume less than the EAR for magnesium. This especially occurs in populations that do not consume recommended amounts of whole grains, pulses, green vegetables. Thus, inadequate magnesium status contributing to cardiovascular disease is widespread, making magnesium a nutrient of public health concern.

Obesity increases the risk for pathological conditions such as bone loss. On the other hand, physical exercise reduces body adiposity. To test the hypothesis that physical activity improves bone quality, we evaluated voluntary running of defined distances on trabecular and cortical microstructure in mice fed a high-fat diet (HFD). Sedentary mice were fed the standard AIN93G diet or the HFD. Mice fed the HFD remained sedentary or were assigned to unrestricted running or 75%, 50%, and 25% of unrestricted running with an average running activity at 8.3, 6.3, 4.2, and 2.1 km per day, respectively. The bone structural differences found in sedentary mice were that HFD, compared with the AIN93G diet, resulted in a lower bone volume fraction (BV/TV) and a higher structure model index (SMI) in vertebrae. Running had a greater effect on trabecular microstructure in femurs than in vertebrae; the decrease in SMI and an increase in trabecular thickness (Tb.Th) were in dose-dependent manners. Running was positively correlated with BV/TV and Tb.Th and inversely correlated with SMI in femurs. The HFD increased plasma concentrations of tartrate-resistant acid phosphatase 5b, a marker of bone resorption, in sedentary mice, while running decreased it in a dose-dependent manner. The findings show that voluntary running improves bone quality in young adult mice fed an HFD. Novelty: The high-fat diet alters bone microstructure by increasing bone resorption. Quantitative voluntary running improves bone microstructure through its attenuation of bone resorption in mice fed a high-fat diet.

The effects of boron on the formation and maintenance of mineralized structures at the molecular level are still not clearly defined. Thus, a study was conducted using MC3T3-E1 cells to determine whether boron affected mRNA expressions of genes associated with bone/alveolar bone formation around the teethMC3T3-E1 (clone 4) cells were cultured in media treated with boric acid at concentrations of 0, 0.1, 10, 100, or 1000 ng/ml. Total RNAs of each group were isolated on day 3. Gene expression profiles were determined by using RT² Profiler PCR micro-array that included 84 genes associated with osteogenic differentiation. Tuftelin1 mRNA expression was upregulated by all boron treatments. The upregulation was confirmed by quantitative RT-PCR using the tuftelin probe. While 100 ng/ml had no effect on the integrin-α2 (Itga2) transcript and 1 ng/ml boric acid induced Itga2 mRNA expression (2.1-fold), 0.1, 10, and 1000 ng/ml boric acid downregulated the integrin-α2 gene transcript 2.2-, 1.5-, and 2.1-fold respectively. While 0.1 ng/ml boric acid induced BMP6, increased BMP1r mRNA expression (1.5 fold) was observed in 1000 ng/ml boric acid treatment. The findings suggest that boron affects the regulation of the tuftelin1 gene in osteoblastic cells. Further studies are needed to establish that the beneficial actions of boron on alveolar bone and tooth formation and maintenance include an effect on the expression of the tuftelin1 gene.