Efficacy of mineral supplementation to growing cattle grazing winter-wheat pasture in northwestern Oklahoma.

Two experiments were conducted to evaluate the efficacy of mineral supplementation to cattle grazing winter-wheat pasture. In experiment 1 (fall), 120 steers and heifers (body weight [BW] = 232 ± 11.4 kg) were assigned randomly to four blocks of replicated pastures during the second week of November in 2008 and 2009 and all herds (6 animals/pasture; 4.9 ha/pasture) were allowed to graze for 84 d. In experiment 2 (spring), 216 steers (BW = 248 ± 7.9 kg) were assigned randomly to five blocks of replicated pastures during the second week of February in 2009 and 2010 and all herds (12 or 6 animals/pasture; 4.9 ha/pasture) were allowed to graze for 84 d. Half the pastures in both experiments received a free-choice mineral mixture (Wheat Pasture Pro; Land O'Lakes Purina Feed, LLC; St. Paul, MN; Ca, 16% and P, 4%); mineral feeders were weighed weekly to determine mineral intake. All pastures were planted in early September of each year (67 kg of seed/ha) and fertilized with 50 kg of urea-N/ha. Standing herbage dry matter was determined midway between weigh dates by clipping wheat forage to the ground along 122 cm of drill rows at 10 locations/pasture. Data were analyzed by ANOVA, with treatment as the fixed effect and pasture, animal sex (experiment 1), and block as random effects. In experiment 1, cattle offered minerals had a 43% faster average daily gain (ADG; P = 0.02, 0.73 kg) than cattle not offered minerals (0.51 kg); hence, supplemented cattle weighed 6% more (P = 0.04; 286 kg) after 84 d than nonsupplemented cattle (271 kg). In experiment 2, cattle offered the mineral supplement had a faster ADG (20% increase; P = 0.04; 1.00 kg) than cattle not offered minerals (0.83 kg). Further, supplemented cattle weighed 4% more (P = 0.03; 326 kg) after 84 d than nonsupplemented cattle (312 kg). In both experiments, daily standing herbage dry matter averaged 1,381 kg/animal and never differed (P ≥ 0.47) between treatments. Mineral intakes averaged 135 (experiment 1) and 124 (experiment 2) g/d, resulting in a cost of supplement to kilogram of added BW gain of $0.53 and $0.64, respectively (assuming a mineral cost of $0.88/kg). Overall, supplementing an appropriate mineral mixture to cattle grazing winter-wheat pasture increased ADG in a cost-effective manner.

Whole-body protein turnover response to short-term high-protein diets during weight loss: a randomized controlled trial.

To determine whole-body protein turnover responses to high-protein diets during weight loss, 39 adults (age, 21±1 years; VO2peak, 48±1 ml kg(-1) min(-1); body mass index, 25±1 kg m(2)) were randomized to diets providing protein at the recommend dietary allowance (RDA), 2 × -RDA or 3 × -RDA. A 10-day weight maintenance period preceded a 21-day, 40% energy deficit. Postabsorptive (FASTED) and postprandial (FED) whole-body protein turnover was determined during weight maintenance (day 10) and energy deficit (day 31) using [1-(13)C]leucine. FASTED flux, synthesis and breakdown were lower (P<0.05) for energy deficit than weight maintenance. Protein flux and synthesis were higher (P<0.05) for FED than FASTED. Feeding attenuated (P<0.05) breakdown during weight maintenance but not energy deficit. Oxidation increased (P<0.05) between dietary protein levels and feeding stimulated oxidation, although oxidative responses to feeding were higher (P<0.05) for energy deficit than weight maintenance. FASTED net balance decreased between dietary protein levels, but in the FED state, net balance was lower for 3 × -RDA as compared with RDA and 2 × -RDA (diet-by-state, P<0.05). Consuming dietary protein at levels above the RDA, particularly 3 × -RDA, during short-term weight loss increases protein oxidation with concomitant reductions in net protein balance.

The Chakaria food system study: household-level, case-control study to identify risk factor for rickets in Bangladesh.

OBJECTIVE: A comprehensive, multiround survey of local food systems in a rickets-endemic area of Bangladesh was conducted to identify household-level risk factors for rickets. DESIGN: A household-level, case-control study was conducted in a rickets-endemic area, Chakaria, with planned comparisons between households with one or more rachitic child and neighboring households with no affected children. SETTING: A rickets-endemic area of southeastern Bangladesh, Chakaria. SUBJECTS AND METHODS: An interview-based survey was conducted in six villages in Chakaria with 199 households with at least one child showing physical signs consistent with rickets and 281 households with no affected children. RESULTS: Households with rachitic children in Chakaria had more children, more pregnant or lactating women, and fewer adults than unaffected households in that community. Affected households tended to rely on farming for their livelihood and tended to have less economic activity as indicated by less outstanding debt than their neighbors. Households with rickets were at significantly greater risk of pneumonia than were other households. Calcium undernutrition was severe and widespread in Chakaria due to a food system that offered very little of the element in accessible forms. Household diets were based on cereals and starchy vegetables. Rice and fish constituted the major source of calcium for most households, although dairy products, when used, were very important calcium sources, particularly for young children. In fact, the use of dairy products was the only household choice that led to substantial increases in the calcium intakes of children, and households that used dairy products tended to show increased calcium intakes for all of their members. CONCLUSIONS: The risk of a Chakarian household having a child with rickets appeared to be related to its economic status. Although this might be expected to be manifest as limitations in food access and/or use, rickets households failed to show a dietary pattern associated with rickets. Calcium undernutrition was prevalent and, thus, would appear to be a predisposing factor for rickets; however, calcium undernutrition was prevalent in Chakarian households with and without rickets. Therefore, it is probable that another precipitating factor(s) play a role(s) in the etiology of rickets in Chakaria.

The selenium requirement of the puppy.

Current selenium (Se) recommendations for the puppy are based on extrapolation from other species (0.11 mg Se/kg diet). The purpose of this study was to experimentally determine the Se requirement in puppies. Thirty beagle puppies (average = 8.8 weeks old) were utilized in a randomized complete block design with age, litter and gender used as blocking criteria. Puppies were fed a low Se (0.04 mg Se/kg diet) torula yeast-based diet for 14 days (pre-test period) after which this same diet was supplemented with five levels of Na2SeO3 for 21 days (experimental period) to construct a response curve (0, 0.13, 0.26, 0.39 or 0.52 mg Se/kg diet). Response variables included Se concentrations and Se-dependent glutathione peroxidase activities (GSHpx) in serum as well as serum total triiodothyronine (TT3), serum total thyroxine (TT4) and serum free T4 (FT4). No significant changes in food intake and body weight gain occurred, and no clinical signs of Se deficiency were observed. A breakpoint for serum GSHpx could not be determined in our study due to analytical difficulties. A broken-line, two-slope response in serum Se occurred with a breakpoint at 0.17 mg Se/kg diet. When Se from the basal diet was added to this estimate, the breakpoint for serum Se equated to 0.21 mg Se/kg diet. TT3 increased linearly with increasing Se intake, whereas TT4 was unchanged. However, the ratio of TT4 : TT3 decreased linearly in response to supplemental Se. In summary, although we estimated the selenium requirement for the puppy based on serum Se, our 0.21 mg Se/kg diet estimate is higher than that seen for adult dogs, kittens, rats or poultry (0.13, 0.15, 0.15 and 0.15 mg Se/kg diet respectively). This difference may be due to the fact that GSHpx was used as the biomarker of Se status.

Status of selenium in prostate cancer prevention.

The complete, 13 years, results of the Nutritional Prevention of Cancer Trial have been analysed, causing some speculation over the robustness of the previously reported findings of reduction of cancer risks by supplements of selenium (Se) to a cohort of older Americans. These analyses confirmed that Se supplementation was associated with marked reductions in risks to total (all-site except skin) carcinomas and to cancers of the prostate and colon-rectum. Of those deep-site treatment effects, the most robust was for prostate cancer, which was more frequent, and was confirmed by serum prostate-specific antigen level. Recent subgroup analyses showed Se supplementation reduced risk of cancer mostly among subjects who entered the trial with plasma Se levels in the bottom tertile of the cohort. Other recent findings have demonstrated that Se treatment can promote apoptosis in prostate cancer cells and, possibly, impair their proliferation through antiangiogenic effects. Thus, a body of basic understanding is developing by which one can understand and evaluate the results of the Nutritional Prevention of Cancer and future clinical trials. This understanding also requires inclusion of the mechanisms of Se transport and cellular uptake, so that appropriate inferences can be made from findings from cell culture systems, which tended to use effective Se doses much larger than relevant to cells in vivo. Also needed is information on the chemical speciation of Se in foods, so that Se delivery can be achieved in ways that are effective in reducing cancer risk and is also safe, accessible and sustainable.

An analysis of cancer prevention by selenium.

The nutritional functions of selenium (Se) are recognized as being due to a number of Se-containing proteins. It is not clear, however, whether any of these function in the anti-tumorigenic effects of Se most of which have been demonstrated for Se exposures greater than those required for selenoprotein expression. Indeed, other anti-tumorigenic mechanisms have been demonstrated for certain Se-metabolites. The Nutritional Prevention of Cancer Trial found supplemental Se (200 microg/day, as Se-enriched yeast) to be associated with significant reductions in cancer risks in subjects with pre-treatment plasma Se concentrations below ca. 120 ng/ml (1.5 nmoles/ml), which level would appear to require food-Se intakes of ca. 1.5 microg/kg body weight/day. However, the putative anti-carcinogenic Se-metabolite(s) should be more relevant than total plasma Se as a supplementation target for cancer prevention. These may be components of the non-protein-bound fraction of Se in plasma, which constitutes 2-4% of total plasma Se.

Selective inhibition of selenocysteine tRNA maturation and selenoprotein synthesis in transgenic mice expressing isopentenyladenosine-deficient selenocysteine tRNA.

Selenocysteine (Sec) tRNA (tRNA([Ser]Sec)) serves as both the site of Sec biosynthesis and the adapter molecule for donation of this amino acid to protein. The consequences on selenoprotein biosynthesis of overexpressing either the wild type or a mutant tRNA([Ser]Sec) lacking the modified base, isopentenyladenosine, in its anticodon loop were examined by introducing multiple copies of the corresponding tRNA([Ser]Sec) genes into the mouse genome. Overexpression of wild-type tRNA([Ser]Sec) did not affect selenoprotein synthesis. In contrast, the levels of numerous selenoproteins decreased in mice expressing isopentenyladenosine-deficient (i(6)A(-)) tRNA([Ser]Sec) in a protein- and tissue-specific manner. Cytosolic glutathione peroxidase and mitochondrial thioredoxin reductase 3 were the most and least affected selenoproteins, while selenoprotein expression was most and least affected in the liver and testes, respectively. The defect in selenoprotein expression occurred at translation, since selenoprotein mRNA levels were largely unaffected. Analysis of the tRNA([Ser]Sec) population showed that expression of i(6)A(-) tRNA([Ser]Sec) altered the distribution of the two major isoforms, whereby the maturation of tRNA([Ser]Sec) by methylation of the nucleoside in the wobble position was repressed. The data suggest that the levels of i(6)A(-) tRNA([Ser]Sec) and wild-type tRNA([Ser]Sec) are regulated independently and that the amount of wild-type tRNA([Ser]Sec) is determined, at least in part, by a feedback mechanism governed by the level of the tRNA([Ser]Sec) population. This study marks the first example of transgenic mice engineered to contain functional tRNA transgenes and suggests that i(6)A(-) tRNA([Ser]Sec) transgenic mice will be useful in assessing the biological roles of selenoproteins.

Selenium in global food systems.

Food systems need to produce enough of the essential trace element Se to provide regular adult intakes of at least 40 microg/d to support the maximal expression of the Se enzymes, and perhaps as much as 300 microg/d to reduce risks of cancer. Deprivation of Se is associated with impairments in antioxidant protection, redox regulation and energy production as consequences of suboptimal expression of one or more of the Se-containing enzymes. These impairments may not cause deficiency signs in the classical sense, but instead contribute to health problems caused by physiological and environmental oxidative stresses and infections. At the same time, supranutritional intakes of Se, i.e. intakes greater than those required for selenocysteine enzyme expression, appear to reduce cancer risk. The lower, nutritional, level is greater than the typical intakes of many people in several parts of the world, and few populations have intakes approaching the latter, supranutritional, level. Accordingly, low Se status is likely to contribute to morbidity and mortality due to infectious as well as chronic diseases, and increasing Se intakes in all parts of the world can be expected to reduce cancer rates.

Impact of selenium and cancer-prevention findings on the nutrition-health paradigm.

Evidence that selenium supplementation can reduce cancer risk is difficult to incorporate in nutrition thinking in which "nutritional essentiality" is the central concept. That concept, which defines nutrient need in terms of indispensability in diets and irreplaceable function in preventing specific deficiency disorders, was not developed to accommodate the function of a nutrient in reducing the risk to chronic disease, particularly when that function is not obligate but may be among several involved in maintaining good health. The findings of Clark et al. (JAMA 276, 1957-1963, 1996; Br J Urol 81, 730-734, 1998) suggest that selenium intakes of approximately twice the levels of the new Recommended Dietary Allowance or more can have such beneficial health effects. Because these intakes are above those required to support its accepted essential biochemical functions and because the maintenance of good general health as much as the prevention of specific deficiency disorders is the goal of public health, it is appropriate to reassess the nutritional essentiality paradigm. This discussion of the development and outcomes of the clinical intervention trials of Larry Clark and colleagues is presented in light of these issues.

Serum selenium and subsequent risk of prostate cancer.

It is suspected that selenium is protective against prostate cancer. To test this hypothesis, we conducted a nested case-control study in a cohort of 9345 Japanese-American men examined between 1971 and 1977. At the time of examination, a blood specimen was obtained, and the serum was frozen. After a surveillance period of more than 20 years, 249 tissue-confirmed incident cases of prostate cancer were identified. Their stored sera and those of 249 matched controls were measured for selenium levels. Odds ratios for prostate cancer, based on quartiles of serum selenium levels, were determined using the General Estimating Equations approach. The multivariate odds ratio for the highest quartile was 0.5 (95% confidence interval, 0.3-0.9) with a two-sided P for trend of 0.02. The inverse association was more notable for cases with advanced disease and for cases diagnosed 5-15 years after phlebotomy. However, the association was mainly present in current or past cigarette smokers rather than nonsmokers, which leads to caution in the interpretation of the results.

Food system-based approaches to improving micronutrient nutrition: the case for selenium.

Micronutrient deficiencies affect nearly half the world's population, impairing child development, reducing work productivity, and increasing mortality and morbidity rates by affecting both infectious and chronic diseases. To feed a growing world, it will be necessary to consider agriculture in the broad context of a food system as an instrument of public health and, thus, to address nutrient balance while also seeking sustainability. Such efforts would include increasing cropping system diversity, enhancing micronutrient outputs and promoting environmental sustainability. Example of this approach are presented for the essential trace element selenium (Se), which at high intakes can reduce cancer risks but is deficient in many parts of the world. Food systems-based approaches are discussed for preventing Se deficiency by enhancing intakes of any of several biologically available forms of Se, and for reducing cancer risk by enhancing intakes of forms of the element that support anti-tumorigenic Se-metabolites.

Effects of topical and oral vitamin E on pigmentation and skin cancer induced by ultraviolet irradiation in Skh:2 hairless mice.

This study investigates whether supplementation with topical RRR-alpha-tocopherol (Eol), topical RRR-alpha-tocopheryl succinate, and oral RRR-alpha-tocopheryl acetate can reduce the incidence of acute and chronic damage to the skin (i.e., sunburn and pigmentation and skin cancer, respectively) induced by ultraviolet (UV) irradiation to mice. Groups of twenty Skh:2 female hairless pigmented mice were treated with 1) lotion vehicle, 2) 5% Eol lotion, 3) 5% topical RRR-alpha-tocopheryl succinate lotion, or 4) lotion vehicle and oral RRR-alpha-tocopheryl acetate. Within each group, 15 mice were exposed to 0.24 J/cm2 of UV-B radiation three times per week. The animals' weights and food intakes were monitored, and the vitamin E concentrations of skin, liver, and adipose tissue were measured to determine whether the topical Eol resulted in significant tissue levels. Skin pigmentation was scored, and the total number of clinically detectable skin tumors per animal was counted weekly. Results showed that the skin concentrations of Eol, as well as levels in the adipose tissue, were increased after topical application. Mice treated with each form of vitamin E showed no signs of toxicity and had significantly less acute and chronic skin damage induced by UV irradiation, as indicated by reduced inflammation and pigmentation and by later onset and lesser incidence of skin cancer.

Nutritional rickets without vitamin D deficiency in Bangladesh.

To understand nutritional rickets in Bangladesh better, 14 rachitic and 13 'unaffected' children were evaluated. Seventy per cent of children with active rickets had no evidence of either vitamin D deficiency or familial rickets. Rickets in Bangladesh is probably related to calcium deficiency. Abnormalities in 'unaffected' children suggest that subclinical calcium insufficiency is common.

Chemopreventive mechanisms of selenium.

The element selenium (Se) was recognized only 40 years ago as being essential in the nutrition of animals and humans. It is recognized as being an essential component of a number of enzymes in which it is present as the amino acid selenocysteine (SeCys). Selenium compounds have also been found to inhibit tumorigenesis in a variety of animal models and recent studies indicate that supplemental Se in human diets may reduce cancer risk. Anti-tumorigenic activities have been associated with Se intakes that are more than sufficient to correct nutritionally deficient status; that is, Se appears to be anti-tumorigenic at intakes that are substantially greater than those associated with maximal expression of the known SeCys-containing enzymes. Therefore, while some cancer protection may involve one or more Se-enzymes, it is probable that anti-tumorigenic functions of Se are discharged by certain Se-metabolites produced in significant amounts at relatively high Se intakes. Thus, Se supplementation of individuals with relatively low or frankly deficient natural intakes of the element can be expected to support enhanced anti-oxidant protection due to increased expression of the Se-dependent glutathione peroxidases and thioredoxin reductase. Higher levels of Se-supplementation can be expected to affect other functions related to tumorigenesis: carcinogen metabolism, immune function, cell cycle regulation and apoptosis. Thus, according to this 2-stage model of the roles of Se in cancer prevention, even individuals with nutritionally adequate Se intakes may benefit from Se-supplementation.

Chemopreventive agents: selenium.

The element selenium (Se) was recognized only 40 years ago as being essential in the nutrition of animals and humans. It is recognized as being an essential component of a number of enzymes, in which it is present as the amino acid selenocysteine. Se compounds have also been found to inhibit tumorigenesis in a variety of animal models, and recent studies indicate that supplemental Se in human diets may reduce cancer risk. The antitumorigenic activities have been associated with Se intakes that correct nutritionally deficient status in animals, as well as higher intakes that are substantially greater than those associated with maximal expression of the selenocysteine-containing enzymes. Therefore, it is proposed that while some cancer protection, particularly that involving antioxidant protection, involves selenoenzymes, specific Se metabolites, which are produced in significant amounts at relatively high Se intakes, also discharge antitumorigenic functions. According to this two-stage model of the roles of Se in cancer prevention, individuals with nutritionally adequate Se intakes may benefit from Se supplementation. Evidence for chemoprevention by Se and for the apparent mechanisms underlying these effects is reviewed to the end of facilitating the development of the potential of Se compounds as cancer chemopreventive agents.

Cellular glutathione peroxidase is the mediator of body selenium to protect against paraquat lethality in transgenic mice.

The antioxidative role of Se-dependent cellular glutathione peroxidase (EC 1.11.1.9, GPX1) in vivo has not been established. Our objective was to determine the effects of GPX1 knockout or overexpression on the susceptibility of mice to paraquat toxicity and the contributions of GPX1, compared with other selenoproteins and vitamin E, to body defenses against such acute oxidative stress. Four experiments were conducted using 111 GPX1 knockout or overexpressing mice and the respective controls. Mice were fed diets supplemented with Se (as sodium selenite) at 0-0.4 mg/kg and/or all-rac-alpha-tocopheryl acetate at 0-75 mg/kg before intraperitoneal injections of 12.5, 50 or 125 mg paraquat/kg body weight. All mice that received 50 or 125 mg paraquat/kg died spontaneously, and the survival time of mice was (independent of dietary levels of Se per se or alpha-tocopheryl acetate) solely a function of tissue GPX1 activity (P < 0.001). Severe acute pulmonary interstitial necrosis was found only in the GPX1 overexpressing mice and the controls that had extended survival time. Thiobarbituric acid reacting substances in postmortem liver inversely correlated with the tissue GPX1 activity and dietary levels of Se and/or alpha-tocopheryl acetate. In contrast, all mice that received 12.5 mg paraquat/kg survived and were killed 2 wk after the injection for tissue collection. Compared with the saline injection, this low dose of paraquat resulted in greater (P < 0.001) liver and lung F2-isoprostanes in both the GPX1 knockout mice and the controls. However, there was no difference in plasma alanine transaminase (EC 2.6.1.2) activity or overt injuries in liver, lung and kidney in either group. Our data indicate that GPX1 is the major, if not the only, metabolic form of body Se that protects mice against the lethal oxidative stress caused by high levels of paraquat; it seems less important, however, in protecting mice against the moderate oxidative stress by the low level of paraquat.

Knockout of cellular glutathione peroxidase affects selenium-dependent parameters similarly in mice fed adequate and excessive dietary selenium.

This study was to determine whether or not effects of the cellular glutathione peroxidase (GPX1) knockout on several Se-dependent parameters in mice were tissue, dietary Se concentration, and selenoprotein specific. A 2 x 3 factorial experiment was conducted with 18 GPX1 knockout mice [GPX1(-)] and 18 controls (3 weeks old, half males and females). These mice were fed a torula yeast diet supplemented with all-rac-alpha-tocopheryl acetate (50 mg/kg of feed) and Se (sodium selenite) at 0, 0.5, or 3.0 mg/kg of feed for 6 weeks. Both kidney GPX1 mRNA levels and liver, kidney, lung, and testis total GPX activities, assayed using hydrogen peroxide, were affected (p < 0.001) by the GPX1 knockout and dietary Se concentrations, whereas kidney extracellular or plasma GPX (GPX3) mRNA levels and phospholipid hydroperoxide GPX (GPX4) activities in the four tissues were affected (p < 0.001) by only dietary Se concentrations. Total GPX activity in testis was reduced approximately 90% (p < 0.01) by the GPX1 knockout. Neither the GPX1 knockout nor the dietary Se concentrations affected mRNA levels of GPX4 in testis or selenoprotein P in kidney. Total liver Se concentrations were not different between the GPX1(-) and control mice at 0 mg Se/kg of feed, but were reduced (p < 0.01) by 61 and 64% in the GPX1(-) mice at 0.5 and 3.0 mg Se/kg of feed, respectively. These results not only confirm the independent expression of GPX3, GPX4, and selenoprotein P from that of GPX1, but also show similar effects of the GPX1 knockout on Se-dependent parameters in mice between different dietary Se concentrations, tissues, and selenoproteins.

Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial.

OBJECTIVE: To test if supplemental dietary selenium is associated with changes in the incidence of prostate cancer. PATIENTS AND METHOD: A total of 974 men with a history of either a basal cell or squamous cell carcinoma were randomized to either a daily supplement of 200 microg of selenium or a placebo. Patients were treated for a mean of 4.5 years and followed for a mean of 6.5 years. RESULTS: Selenium treatment was associated with a significant (63%) reduction in the secondary endpoint of prostate cancer incidence during 1983-93. There were 13 prostate cancer cases in the selenium-treated group and 35 cases in the placebo group (relative risk, RR=0.37, P=0.002). Restricting the analysis to the 843 patients with initially normal levels of prostate-specific antigen (< or = 4 ng/mL), only four cases were diagnosed in the selenium-treated group and 16 cases were diagnosed in the placebo group after a 2 year treatment lag, (RR=0.26 P=0.009). There were significant health benefits also for the other secondary endpoints of total cancer mortality, and the incidence of total, lung and colorectal cancer. There was no significant change in incidence for the primary endpoints of basal and squamous cell carcinoma of the skin. In light of these results, the 'blinded' phase of this trial was stopped early. CONCLUSIONS: Although selenium shows no protective effects against the primary endpoint of squamous and basal cell carcinomas of the skin, the selenium-treated group had substantial reductions in the incidence of prostate cancer, and total cancer incidence and mortality that demand further evaluation in well-controlled prevention trials.