Category Archives: Minerals

Potassium Citrate or Bicarbonate, but Not Chloride, Decrease Acid Load

Abstract

Contrasting effects of various potassium salts on renal citrate excretion.

Mechanisms for the citraturic response to potassium citrate treatment were sought by assessing renal citrate clearance and acid-base status after oral administration of potassium citrate, potassium bicarbonate, and potassium chloride. After 2 weeks of treatment of eight patients with stones at a dose of 80 meq/day, urinary citrate rose significantly from 2.5 +/- 1.6 mmol/day (no drug) to 5.1 +/- 1.7 mmol/day with potassium citrate and to 4.5 +/- 1.5 mmol/day with potassium bicarbonate (P less than 0.05), but did not change significantly with potassium chloride. Citrate clearance increased from 8.0 to 27.4 mL/min with potassium citrate and 25.8 mL/min with potassium bicarbonate (P less than 0.05), but did not increase with potassium chloride. Both potassium citrate and potassium bicarbonate significantly raised urinary bicarbonate and decreased urinary ammonium, titratable acid, and net acid excretion. Potassium chloride was without effect. Effects of potassium citrate on urinary citrate, citrate clearance, and acid-base status tended to be more prominent than those of potassium bicarbonate, but these changes were not significant. Thus, the citraturic action of potassium citrate is largely accountable for by provision of an alkali load. Potassium itself had no effect in the absence of potassium deficiency.

Sakhaee K, Alpern R, Jacobson HR, Pak CY
J. Clin. Endocrinol. Metab. Feb 1991
PMID: 1899422

Arginine May Increase Bone Formation by Increasing Silicon Absorption in Rats

Abstract

Dietary silicon and arginine affect mineral element composition of rat femur and vertebra.

Both arginine and silicon affect collagen formation and bone mineralization. Thus, an experiment was designed to determine if dietary arginine would alter the effect of dietary silicon on bone mineralization and vice versa. Male weanling Sprague-Dawley rats were assigned to groups of 12 in a 2 x 2 factorially arranged experiment. Supplemented to a ground corn/casein basal diet containing 2.3 microg Si/g and adequate arginine were silicon as sodium metasilicate at 0 or 35 microg/g diet and arginine at 0 or 5 mg/g diet. The rats were fed ad libitum deionized water and their respective diets for 8 wk. Body weight, liver weight/body weight ratio, and plasma silicon were decreased, and plasma alkaline phosphatase activity was increased by silicon deprivation. Silicon deprivation also decreased femoral calcium, copper, potassium, and zinc concentrations, but increased the femoral manganese concentration. Arginine supplementation decreased femoral molybdenum concentration but increased the femoral manganese concentration. Vertebral concentrations of phosphorus, sodium, potassium, copper, manganese, and zinc were decreased by silicon deprivation. Arginine supplementation increased vertebral concentrations of sodium, potassium, manganese, zinc, and iron. The arginine effects were more marked in the silicon-deprived animals, especially in the vertebra. Germanium concentrations of the femur and vertebra were affected by an interaction between silicon and arginine; the concentrations were decreased by silicon deprivation in those animals not fed supplemental arginine. The change in germanium is consistent with a previous finding by us suggesting that this element may be physiologically important, especially as related to bone DNA concentrations. The femoral and vertebral mineral findings support the contention that silicon has a physiological role in bone formation and that arginine intake can affect that role.

Seaborn CD, Nielsen FH
Biol Trace Elem Res Dec 2002
PMID: 12462747

Arginine is an essential amino acid for the rat. In animals L-arginine apparently induces growth hormone and insulin-like growth factor-1 responses and stimulates nitric oxide synthase. Growth hormone and insulin-like growth factor-1 are important mediators of bone turnover and osteoblastic bone formation, whereas nitric oxide is a potent inhibitor of osteoclastic bone resorption (1). By affecting these physiological regulators of bone remodeling, L-arginine could potentially increase bone formation over bone resorption and, consequently, increase bone mass.

There is experimental evidence suggesting that arginine supplementation promotes bone formation. A mixture of lactose, L-arginine, and L-lysine improved fracture healing of rabbits subjected to an osteotomy of the left fibula (2). These authors suggested that arginine was involved not only in the increase of intestinal calcium absorption but also in collagen synthesis. Although there is evidence that L-arginine affects bone maintenance minimal attention has been given to the possible interaction between arginine and other macro and/or trace minerals, including silicon associated with mineralized bone formation and remodeling.

Silicon can affect bone formation and remodeling (3). The basic amino acids such as arginine can increase silicon absorption (4). Therefore the effects of silicon on bone mineralization may be modified by the amount of arginine in the diet….

Review: Nutrients Involved in Maintaining Healthy Bone

Abstract

Update on nutrients involved in maintaining healthy bone.

Osteoporosis is a leading cause of morbidity and mortality in the elderly and influences quality of life, as well as life expectancy. Currently, there is a growing interest among the medical scientists in search of specific nutrients and/or bioactive compounds of natural origin for the prevention of disease and maintenance of bone health. Although calcium and vitamin D have been the primary focus of nutritional prevention of osteoporosis, a recent research has clarified the importance of several additional nutrients and food constituents. Based on this review of the literature, supplementation with vitamins B, C, K, and silicon could be recommended for proper maintenance of bone health, although further clinical studies are needed. The results of studies on long-chain polyunsaturated fatty acids, potassium, magnesium, copper, selenium, and strontium are not conclusive, although studies in vitro and in animal models are interesting and promising.

Rondanelli M, Opizzi A, Perna S, Faliva MA
Endocrinol Nutr Apr 2013
PMID: 23273614

IP-6 May Impair Bioavailability of Iron, Calcium, and Zinc in Chinese

Abstract

Phytate intake and molar ratios of phytate to zinc, iron and calcium in the diets of people in China.

To assess the phytate intake and molar ratios of phytate to calcium, iron and zinc in the diets of people in China.
2002 China Nationwide Nutrition and Health Survey is a cross-sectional nationwide representative survey on nutrition and health. The information on dietary intakes was collected using consecutive 3 days 24 h recall by trained interviewers.
The data of 68 962 residents aged 2-101 years old from 132 counties were analyzed.
The median daily dietary intake of phytate, calcium, iron and zinc were 1186, 338.1, 21.2 and 10.6 mg, respectively. Urban residents consumed less phytate (781 vs 1342 mg/day), more calcium (374.5 vs 324.1 mg/day) and comparable amounts of iron (21.1 vs 21.2 mg/day) and zinc (10.6 vs 10.6 mg/day) than their rural counterparts. A wide variation in phytate intake among residents from six areas was found, ranging from 648 to 1433 mg/day. The median molar ratios of phytate to calcium, iron, zinc and phytate x calcium/zinc were 0.22, 4.88, 11.1 and 89.0, respectively, with a large variation between urban and rural areas. The phytate:zinc molar ratios ranged from 6.2 to 14.2, whereas the phytate x calcium/zinc molar ratios were from 63.7 to 107.2. The proportion of subjects with ratios above the critical values of phytate to iron, phytate to calcium, phytate to zinc and phytate x calcium/zinc were 95.4, 43.7, 23.1 and 8.7%, respectively. All the phytate/mineral ratios of rural residents were higher than that of their urban counterparts.
The dietary phytate intake of people in China was higher than those in Western developed countries and lower than those in developing countries. Phytate may impair the bioavailability of iron, calcium and zinc in the diets of people in China.

Ma G, Li Y, Jin Y, Zhai F…
Eur J Clin Nutr Mar 2007
PMID: 16929240

Iron Overload Inhibits Osteoblasts via Oxidative Stress

Abstract

Iron overload inhibits osteoblast biological activity through oxidative stress.

Iron overload has recently been connected with bone mineral density in osteoporosis. However, to date, the effect of iron overload on osteoblasts remains poorly understood. The purpose of this study is to examine osteoblast biological activity under iron overload. The osteoblast cells (hFOB1.19) were cultured in a medium supplemented with different concentrations (50, 100, and 200 μM) of ferric ammonium citrate as a donor of ferric ion. Intracellular iron was measured with a confocal laser scanning microscope. Reactive oxygen species (ROS) were detected by 2,7-dichlorofluorescin diacetate fluorophotometry. Osteoblast biological activities were evaluated by measuring the activity of alkaline phosphatase (ALP) and mineralization function. Results indicated that iron overload could consequently increase intracellular iron concentration and intracellular ROS levels in a concentration-dependent manner. Additionally, ALP activity was suppressed, and a decline in the number of mineralized nodules was observed in in vitro cultured osteoblast cells. According to these results, it seems that iron overload probably inhibits osteoblast function through higher oxidative stress following increased intracellular iron concentrations.

He YF, Ma Y, Gao C, Zhao GY…
Biol Trace Elem Res May 2013
PMID: 23334864

Mild Low Iron Promotes Osteoblasts; Excess or Serious Low Iron Bad In Vitro

Abstract

A comparison of the biological activities of human osteoblast hFOB1.19 between iron excess and iron deficiency.

Bone metabolism has a close relationship with iron homeostasis. To examine the effects of iron excess and iron deficiency on the biological activities of osteoblast in vitro, human osteoblast cells (hFOB1.19) were incubated in a medium supplemented with 0-200 μmol/L ferric ammonium citrate and 0-20 μmol/L deferoxamine. The intracellular iron was measured by a confocal laser scanning microscope. Proliferation of osteoblasts was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apoptotic cells were detected using annexin intervention V/PI staining with a flow cytometry. Alkaline phosphatase (ALP) activity was measured using an ALP assay kit. The number of calcified nodules and mineral area was evaluated by von Kossa staining assay. The expressions of type I collagen and osteocalcin of cultured osteoblasts were detected by reverse transcriptase polymerase chain reaction and Western blot. Intracellular reactive oxygen species (ROS) was measured using the oxidation-sensitive dye 2,7-dichlorofluorescin diacetate by flow cytometry. The results indicated that excessive iron inhibited osteoblast activity in a concentration-dependent manner. Low iron concentrations, in contrast, produced a biphasic manner on osteoblasts: mild low iron promoted osteoblast activity, but serious low iron inhibited osteoblast activity. Osteogenesis was optimal in certain iron concentrations. The mechanism underlying biological activity invoked by excessive iron may be attributed to increased intracellular ROS levels.

Zhao GY, Zhao LP, He YF, Li GF…
Biol Trace Elem Res Dec 2012
PMID: 23054865

Iron Overload Inhibits Osteoblasts in Mouse and Rat Cells

Abstract

Excess iron inhibits osteoblast metabolism.

Hemochromatosis is an iron overload disorder associated with osteopenia and osteoporosis. To learn more about the effects of iron on bone cells, we examined the effects of ferric ion on the proliferation, differentiation, and mineralization of two types of cultured osteoblasts, the cell line MC3T3-E1 and rat calvarial osteoblast-like (ROB) cells. We used ferric ammonium citrate (FAC) as a donor of ferric ion, and FAC inhibited the proliferation of MC3T3-E1 cells in a dose-dependent manner. FAC (0.1-1 microg/ml) inhibited indices of osteoblast differentiation, such as the expression of type I collagen (mRNA and protein), the activity of alkaline phosphatase, and the deposition of calcium by osteoblasts. These results suggest that iron overload might give rise to osteoporosis by inhibiting osteoblast proliferation and differentiation.

Yamasaki K, Hagiwara H
Toxicol. Lett. Dec 2009
PMID: 19735707

Iron Deficiency Causes Lower Bone Density in Rats

Abstract

Iron deficiency negatively affects vertebrae and femurs of rats independently of energy intake and body weight.

The question of whether iron deficiency has direct adverse effects on vertebral trabecular bone and long bones was answered by this study. Four groups of female weanling rats were fed for 5 wk diets that were 1) control; 2) calcium restricted, 1.0 g Ca/kg diet; 3) iron deficient, <8 mg Fe/kg diet; or 4) control, pair-fed to the iron-deficient group. Whole body and femur DEXA analysis revealed that calcium-restricted and iron-deficient rats had lower bone mineral density (BMD) and content (BMC) than pair-fed and control rats. However, pair-fed rats also had decreased BMD and BMC compared to control rats. The third lumbar trabecular bone microarchitecture in both diet-restricted groups had decreased bone volume fraction (BV/TV) and trabecular number and thickness, a less favorable structural model index, and increased trabecular separation compared with the controls and the pair-fed groups as determined by microcomputer tomography. The control and pair-fed groups did not differ from one another, suggesting that iron deficiency and calcium restriction affected vertebrae independently of food intake and body weight. Finite element analysis revealed lower force to compress the vertebrae and lower stiffness but greater von Mises stress in calcium-restricted and iron-deficient groups compared to the control and pair-fed groups. Urinary deoxypyridinium crosslinks, serum osteocalcin, and cholcalciferol were increased in calcium-restricted rats compared to the other 3 groups. Using micro-CT imaging technology, this study demonstrated microarchitectural pathology due to iron deficiency upon vertebral trabecular bone compared to the control and pair-fed rats, although not to the same extent as severe calcium restriction.

Medeiros DM, Stoecker B, Plattner A, Jennings D…
J. Nutr. Nov 2004
PMID: 15514276 | Free Full Text

Iron Increase Associated with Decreased Bone Density During Spaceflight

Abstract

Iron status and its relations with oxidative damage and bone loss during long-duration space flight on the International Space Station.

Increases in stored iron and dietary intake of iron during space flight have raised concern about the risk of excess iron and oxidative damage, particularly in bone.
The objectives of this study were to perform a comprehensive assessment of iron status in men and women before, during, and after long-duration space flight and to quantify the association of iron status with oxidative damage and bone loss.
Fasting blood and 24-h urine samples were collected from 23 crew members before, during, and after missions lasting 50 to 247 d to the International Space Station.
Serum ferritin and body iron increased early in flight, and transferrin and transferrin receptors decreased later, which indicated that early increases in body iron stores occurred through the mobilization of iron to storage tissues. Acute phase proteins indicated no evidence of an inflammatory response during flight. Serum ferritin was positively correlated with the oxidative damage markers 8-hydroxy-2′-deoxyguanosine (r = 0.53, P < 0.001) and prostaglandin F2α (r = 0.26, P < 0.001), and the greater the area under the curve for ferritin during flight, the greater the decrease in bone mineral density in the total hip (P = 0.031), trochanter (P = 0.006), hip neck (P = 0.044), and pelvis (P = 0.049) after flight.
Increased iron stores may be a risk factor for oxidative damage and bone resorption.

Zwart SR, Morgan JL, Smith SM
Am. J. Clin. Nutr. Jul 2013
PMID: 23719548

Zinc Acexamate Stimulates Fracture Healing in Rats at Different Doses

Abstract

Stimulatory effect of zinc acexamate administration on fracture healing of the femoral-diaphyseal tissues in rats.

The effect of zinc acexamate on fracture healing of the femoral-diaphyseal tissues in rats was investigated in vivo. Zinc acexamate (0.3 and 10.0 mg Zn/100 g body weight per day) was orally administered to rats (4 weeks old) surgically fractured the femoral diaphysis for 14 to 28 days. Calcium content and alkaline phosphatase activity in the femoral-diaphyseal tissues were significantly decreased in rats with fracture healing, while bone acid phosphatase activity and protein content were markedly increased. The administration of zinc acexamate (10.0 mg Zn/100 g) for 28 days caused a significant increase in calcium content, alkaline and acid phosphatases activities, protein and deoxyribonucleic acid (DNA) contents in the femoral-diaphyseal tissues of rats with fracture healing. With the lower dose (3.0 mg Zn/100 g), zinc compound had a partial effect on bone components. Femoral mineral density in rats with fracture healing was significantly increased by the administration of zinc acexamate (10.0 mg Zn/100 g) for 28 days. Femoral-diaphyseal zinc content was significantly decreased in rats with fracture healing. This decrease was completely restored by the administration of zinc acexamate (10.0 mg Zn/100 g) for 28 days. The present study suggests that the supplement of zinc compound stimulates fracture healing of the femoral-diaphyseal tissues in rats.

Igarashi A, Yamaguchi M
Gen. Pharmacol. Apr 1999
PMID: 10323487