Forrest H. Nielsen

Magnesium, inflammation, and obesity in chronic disease

About 60% of adults in the United States do not consume the estimated average requirement for magnesium, but widespread pathological conditions attributed to magnesium deficiency have not been reported. Nevertheless, low magnesium status has been associated with numerous pathological conditions characterized as having a chronic inflammatory stress component. In humans, deficient magnesium intakes are mostly marginal to moderate (approximately 50% to <100% of the recommended dietary allowance). Animal experiments indicate that signs of marginal-to-moderate magnesium deficiency can be compensated or exacerbated by other factors influencing inflammatory and oxidative stress; recent studies suggest a similar happening in humans. This suggestion may have significance in obesity, which is characterized as having a chronic low-grade inflammation component and an increased incidence of a low magnesium status. Marginal-to-moderate magnesium deficiency through exacerbating chronic inflammatory stress may be contributing significantly to the occurrence of chronic diseases such as atherosclerosis, hypertension, osteoporosis, diabetes mellitus, and cancer.

Nickel Deficiency Diminishes Sperm Quantity and Movement in Rats

Early studies on nickel essentiality with rats and goats indicated that nickel deprivation impaired reproductive performance. Nickel also has been found to influence cyclic nucleotide gated channels (CNG); these types of channels are important in sperm physiology. Thus, two experiments were conducted to test the hypothesis that nickel deficiency affects sperm physiology in a manner consistent with nickel having an essential function related to CNG channel functions. The experiments were factorially arranged with four treatment groups of eight weanling rats in each. In experiment 1, the treatments were supplemental dietary nickel of 0 and 1 mg/kg and Nω-nitro-l-arginine methyl ester (l-NAME, a nitric oxide synthase inhibitor) added to the drinking water (50 mg/100 mL) the last 3 wk of an 8-wk experiment. In experment 2, the treatments were supplemental dietary nickel at 0 and 1 mg/kg and supplemental dietary sodium chloride (NaCl) at 0 and 80 g/kg. The NaCl and l-NAME variables were included to act as stressors affecting CNG channel activity. The basal diet contained per kilogram about 27 µg of nickel and 1 g of sodium. After 8 wk in experiment 1 and 16 wk in experiment 2, urine while fasting and testes and epididymis in both experiments, and seminal vesicles and prostates in experiment 2 were harvested for analysis. Nickel deprivation significantly decreased spermatozoa motility and density in the epididymides, epididymal transit time of spermatozoa, and testes sperm production rate. Nickel deficiency also significantly decreased the weights of the seminal vesicles and prostate glands. Excessive NaCl had no effect on sperm physiology; however, it decreased prostate gland weights. The findings support the hypothesis that nickel has an essential function that possibly could affect reproductive performance in higher animals, perhaps through affecting a CNG channel function.

Boron in human and animal nutrition

This review describes the findings from human and animal studies indicating that B is a dynamic trace element which, in physiological amounts, can affect the metabolism or utilisation of numerous other substances involved in life processes including macrominerals, energy substrates such as triglycerides and glucose, nitrogen containing substances such as amino acids and proteins, reactive oxygen species, and estrogen. Through these effects, B can affect the function or composition of several body systems, including the brain, skeleton and immune system, generally in a beneficial fashion. Moreover, homeostatic mechanisms apparently exist for B because it is rapidly excreted in the urine, does not accumulate in tissues, and is maintained in a relatively narrow range of concentrations in blood of healthy individuals. Thus, even though B has not been conclusively established as essential because a biochemical function for it has not been identified, its beneficial actions suggest that an intake of over 1 mg day-1 (but probably not more than 13 mg day-1) is desirable; diets low in fruits, vegetables, legumes and nuts may not provide this amount of B. Boron may be of more practical nutritional importance than currently acknowledged.

Is boron nutritionally relevant

Evidence from numerous laboratories using a variety of experimental models, including humans, shows that boron is a bioactive beneficial element. Much evidence has come from studies that did not require nutritional or environmental stressors or fastidious methods in diet preparation or environmental control. The evidence includes deprivation studies showing that boron is necessary for some higher animals to complete the life cycle, and that realistic low boron intakes result in impaired bone health, brain function, and immune response. Thus, low boron intake is a relevant nutritional concern, which diets rich in fruits, vegetables, nuts, and pulses can prevent.

Silicon Deprivation Decreases Collagen Formation in Wounds and Bone, and Ornithine Transaminase Enzyme Activity in Liver

We have shown that silicon (Si) deprivation decreases the collagen concentration in bone of 9-wk-old rats. Finding that Si deprivation also affects collagen at different stages in bone development, collagen-forming enzymes, or collagen deposition in other tissues would have implications that Si is important for both wound healing and bone formation. Therefore, 42 rats in experiment 1 and 24 rats in experiment 2 were fed a basal diet containing 2 or 2.6 µg Si/g, respectively, based on ground corn and casein, and supplemented with either 0 or 10 µg Si/g as sodium metasilicate. At 3 wk, the femur was removed from 18 of the 42 rats in experiment 1 for hydroxyproline analysis. A polyvinyl sponge was implanted beneath the skin of the upper back of each of the 24 remaining rats. Sixteen hours before termination and 2 wk after the sponge had been implanted, each rat was given an oral dose of14C-proline (1.8 µCi/100 g body wt). The total amount of hydroxyproline was significantly lower in the tibia and sponges taken from Si-deficient animals than Si-supplemented rats. The disintegrations per minute of14C-proline were significantly higher in sponge extracts from Si-deficient rats than Si-supplemented rats. Additional evidence of aberrations in proline metabolism with Si deprivation was that liver ornithine aminotransferase was significantly decreased in Si-deprived animals in experiment 2. Findings of an increased accumulation of14C-proline and decreased total hydroxyproline in implanted sponges and decreased activity of a key enzyme in proline synthesis (liver ornithine aminotransferase) in Si-deprived animals indicates an aberration in the formation of collagen from proline in sites other than bone that is corrected by Si. This suggests that Si is a nutrient of concern in wound healing as well as bone formation.

The emergence of boron as nutritionally important throughout the life cycle

is needed or beneficial for many of life processes including embryogenesis, bone growth and maintenance, immune function, psychomotor skills, and cognitive functions suggest that this prediction will become true. The surprising thing about this development is that only 20 y ago students in the biological and medical sciences were being taught that boron was essential for plants but not for animals. In fact, at the time the first report about the possible nutritional importance of boron appeared,2 boron was generally regarded as an element of only toxicologic concern, especially in the hospital setting. Now that the opinion about the nutritional importance of boron is changing, a question that has come to the fore is: Why wasn’t this recognized sooner? A reasonable answer to that question is that boron apparently has a biochemical function that is very subtle. Moreover, this role apparently is one that allows optimal functioning of other nutrients or hormones and thus is overlooked as attention is directed toward altering the intake of the substance whose suboptimal metabolism is directly involved in a pathologic consequence (e.g., calcium supplementation to prevent bone loss). In 1987, based on assorted bits of evidence, mainly from plants, it was suggested that boron, through an effect on the cell membrane, affected calcium metabolism and hormone action in higher forms of life.3 In 1991, additional findings from plants and animals were used to change this suggestion to the hypothesis that boron has a role in cell-membrane function or stability such that it influences the response to hormone action, transmembrane signaling, or transmembrane movement of regulatory cations or anions.4 Testing of this hypothesis has been difficult. Nonetheless, many of the recent findings showing that boron is needed or beneficial throughout the life cycle support this hypothesis.

Ultratrace elements in nutrition: Current knowledge and speculation

The term ultratrace element has been defined as an element with an established, estimated, or suspected requirement generally indicated by μg/day for humans. Between 1970 and 1984, it was suggested that 11 elements should be added to the list of ultratrace elements that included chromium, molybdenum, and selenium; these elements were arsenic, boron, bromine, cadmium, fluorine, lead, lithium, nickel, silicon, tin, and vanadium. Since 1984, it has been suggested that three more elements, aluminum, germanium, and rubidium, should be added to the list, and circumstantial evidence has continued to accumulate which indicates that several of the ultratrace elements in addition to iodine and selenium, particularly arsenic, boron, chromium, nickel, silicon, and vanadium, are more important in nutrition than currently acknowledged. This evidence includes findings from human studies suggesting that boron has an essential function or beneficial effect in calcium metabolism, brain function, energy metabolism, and perhaps immune processes; and that chromium has an essential function in potentiating insulin action in the metabolism of glucose and lipids, and/or a beneficial effect on diabetes resulting from inadequate synthesis of insulin or insulin resistance. The major shortcoming that has prevented the unequivocal acceptance of the nutritional importance of any of the ultratrace elements suggested as being essential since 1970 and chromium is that a specific biochemical function has not been identified for any of these elements. The current status of the evidence suggesting essentiality, the possible biological function, and speculated dietary need for each of the 15 elements without an identified biochemical function is reviewed. J. Trace Elem. Exp. Med. 11:251–274, 1998. Published 1998 Wiley-Liss, Inc.1

New Essential Trace Elements for the Life Sciences

The possible importance of some new essential trace elements in nutrition is discussed. Most likely, insufficient intake of a specific trace element becomes obvious only when the body is stressed in some way that enhances the need for that element; this has been supported by recent findings with selenium. The trace elements boron and copper may be of nutritional significance in a manner similar to selenium. When the diets of animals and humans are manipulated to cause possible changes in cellular integrity or in hormone responsiveness, a large number of responses to dietary boron occur. The findings indicate that boron is important for optimal calcium and, thus, bone metabolism. High dietary cystine and fructose exacerbate the signs of copper deficiency in rats; this indicates that the response to copper deficiency by humans would vary with the amino acid and carbohydrate composition of the diet. There is some evidence that chromium, molybdenum, nickel, arsenic, and vanadium may also be of nutritional significance under stress conditions. In other words, an increasing number of studies have been performed that have examined the importance of trace element nutriture in various forms of nutritional, metabolic, hormonal, or physiologic stress in animals and humans. These studies indicate that situations will be found in which a trace element is of nutritional significance. It is likely that some of the trace elements are more important in human nutrition than is now generally acknowledged.

Dietary Magnesium Deficiency Induces Heart Rhythm Changes, Impairs Glucose Tolerance, and Decreases Serum Cholesterol in Post Menopausal Women

Objective: To determine whether or not dietary magnesium restriction to about 33% of the Recommended Dietary Allowance (RDA) causes changes in glucose, cholesterol and electrolyte metabolism that could lead to pathologic consequences. Design: The length of the experiment was 136 days. Subjects were fed a basal Western-type diet that provided 4.16 mmol (101 mg) magnesium per 8.4 MJ (2000 kcal) for 78 days then replenished with magnesium by supplementing the diet with 200 mg magnesium as the gluconate per day for 58 days. If a subject exhibited adverse heart rhythm changes before 78 days of depletion were completed, she entered the repletion period early. Setting: The metabolic research unit of the Grand Forks Human Nutrition Research Center. Subjects: A total of 14 post menopausal women were recruited by advertisement throughout the United States. Thirteen women (ages 47 to 75 years) completed the study. Results: During magnesium depletion, heart rhythm changes appeared in 5 women and resulted in 4 prematurely entering the magnesium repletion period (42 to 64 days of depletion instead of 78). Three women exhibited atrial fibrillation and flutter that responded quickly to magnesium supplementation. Magnesium deprivation resulted in a non-positive magnesium balance that became highly positive with magnesium repletion. Magnesium deprivation decreased red blood cell membrane magnesium, serum total cholesterol and erythrocyte superoxide dismutase concentrations, increased the urinary excretion of sodium and potassium, and increased serum glucose concentration. Conclusions: Magnesium balance may be a suitable indicator of magnesium depletion under experimental conditions. Magnesium deficiency resulting from feeding a diet that would not be considered having an atypical menu induces heart arrhythmias, impairs glucose homeostasis, and alters cholesterol and oxidative metabolism in post menopausal women. A dietary intake of about 4.12 mmol (100 mg) Mg/8.4 MJ is inadequate for healthy adults and may result in compromised cardiovascular health and glycemic control in post menopausal women.

Update on human health effects of boron.

In vitro, animal, and human experiments have shown that boron is a bioactive element in nutritional amounts that beneficially affects bone growth and central nervous system function, alleviates arthritic symptoms, facilitates hormone action and is associated with a reduced risk for some types of cancer. The diverse effects of boron suggest that it influences the formation and/or activity of substances that are involved in numerous biochemical processes. Several findings suggest that this influence is through the formation of boroesters in biomolecules containing cis-hydroxyl groups. These biomolecules include those that contain ribose (e.g., S-adenosylmethionine, diadenosine phosphates, and nicotinamide adenine dinucleotide). In addition, boron may form boroester complexes with phosphoinositides, glycoproteins, and glycolipids that affect cell membrane integrity and function. Both animal and human data indicate that an intake of less than 1.0mg/day inhibits the health benefits of boron. Dietary surveys indicate such an intake is not rare. Thus, increasing boron intake by consuming a diet rich in fruits, vegetables, nuts and pulses should be recognized as a reasonable dietary recommendation to enhance health and well-being.