scholarly journals Review of potential risks associated with supplemental dietary exposure to nitrate-containing compounds in swine — a paradox in light of emerging benefits

2021 ◽  
Author(s):  
Candace L Doepker ◽  
Melissa M Heintz ◽  
Jennifer van de Ligt ◽  
Daniele S Wikoff
Keyword(s):  
Drinking Water ◽  
Adverse Effects ◽  
Vitamin A ◽  
Case Reports ◽  
Life Stage ◽  
Calcium Nitrate ◽  
Weight Of Evidence ◽  
Dietary Nitrate ◽  
Nitrate Supplementation ◽  
Potential Risks

Abstract Calcium nitrate has been reported to benefit reproductive outcomes in sows and their offspring when administered via the feed (15–19 mg/kg-bw/day) during the periparturient period. Traditionally, dietary nitrate had been considered a methemoglobinemia (MetHb) risk in swine. Similar hazard concerns have existed in humans, but a recent benefit/risk analysis established that nitrate levels associated with well-recognized health benefits outweigh potential risks. A similar benefit/risk perspective in swine was lacking and challenged by sparse published hazard data, often referenced within larger reviews related to all livestock. The objective of this review was to better characterize the potential for adverse health and performance effects reported in the literature for swine consuming nitrate, and to provide metrics for evaluating the reliability of the studies reviewed. Supplemental exposure via feed or drinking water was considered for any life stage, dose, and exposure duration. More than 30 relevant studies, including case reports and reviews, examined calcium, potassium, sodium, or unspecified nitrate salts at doses up to 1,800 mg nitrate/kg-bw/day for exposures ranging from 1 to 105 days. The studies primarily evaluated weight gain, blood methemoglobin levels, or vitamin A homeostasis in sows or growing swine. An extensive review of the literature showed reports of adverse effects at low nitrate doses to be of low reliability. Conversely, reliable studies corroborate nitrate intake from feed or drinking water at levels equal to or greater than EFSA’s no-observed-adverse-effect level (NOAEL) for swine of 410 mg nitrate/kg-bw/day, with no MetHb or other adverse effects on reproduction, growth, or vitamin A levels. Using a weight-of-evidence evaluation, we have moderate to high confidence that the NOAEL for nitrate supplementation in swine is likely between 600 and 800 mg/kg-bw/day. These levels are several-fold higher than dietary nitrate concentrations (19 mg/kg-bw/day) that are known to benefit birth outcomes in sows. This review elucidates the quality and reliability of the information sources historically used to characterize nitrate in swine feed as a contaminant of concern. Results from this evaluation can assist risk managers (e.g., regulatory officials and veterinarians) in consideration of proposed benefits, as well as reassuring swine producers that low-level nitrate supplementation is not anticipated to be a concern.

scholarly journals Maternal Dietary Nitrate Supplementation Lowers Incidence of Stillbirth in Hyper Prolific Sows under Commercial Circumstances

Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3364
Author(s):  
Moniek van den Bosch ◽  
Bram Bronsvoort ◽  
Bas Kemp ◽  
Henry van den Brand
Keyword(s):  
Nitric Oxide ◽  
Calcium Nitrate ◽  
Current Experiment ◽  
Dietary Nitrate ◽  
Commercial Farm ◽  
Nitrate Supplementation ◽  
Piglet Growth ◽  
Cross Fostering

The objective of the current experiment was to investigate whether or not maternal dietary nitrate supplementation, a nitric oxide (NO) precursor, could reduce piglet losses under commercial circumstances. In the current experiment, 120 hyper prolific gilts and sows (Landrace x Yorkshire: Danbred) on a commercial farm in Denmark received either a control lactation diet or a lactation diet containing 0.1% of calcium nitrate (containing 63.1% of nitrate) from approximately 5 days pre-farrowing until day 4 of lactation. The number of piglets born total, alive, and stillborn, as well as birth weights, weights after cross-fostering (approximately 1 day of age), 24 h after cross-fostering, day 3 of age, and at weaning was recorded. Placentas of sows were collected after expulsion and scored on redness. No effect of nitrate supplementation was found on piglet weight, piglet growth, placental redness score, and pre-weaning mortality during lactation. Maternal dietary nitrate supplementation decreased stillbirth percentage with 2.5% (9.9 vs. 7.4%; p = 0.05). It can be concluded that maternal dietary nitrate supplementation shows the potential to decrease the incidence of stillbirth in hyper prolific sows.

scholarly journals Effects of maternal dietary nitrate supplementation during the perinatal period on piglet survival, body weight, and litter uniformity

2019 ◽  
Vol 3 (1) ◽  
pp. 464-472
Author(s):  
Moniek van den Bosch ◽  
Jan Wijnen ◽  
Irene B van de Linde ◽  
Ad A M van Wesel ◽  
Delphine Melchior ◽  
...  
Keyword(s):  
Body Weight ◽  
Maternal Diet ◽  
Average Daily Gain ◽  
Calcium Nitrate ◽  
Optimal Dose ◽  
Perinatal Period ◽  
Control Treatment ◽  
Dietary Nitrate ◽  
No Formation ◽  
Nitrate Supplementation

Abstract The objective of this study was to evaluate effects of different dosages of dietary nitrate supplementation to sows from d 108 of gestation until d 5 of lactation on reproductive performance of sows and piglet performance from birth until weaning. Dietary nitrate supplementation leads to nitric oxide (NO) formation that can potentially increase blood flow to the fetuses (by the vasodilative effect of NO), leading to a decrease in the loss of potential viable piglets in the form of stillbirth and preweaning mortality. Three hundred and five gilts and sows were allocated to one of six diets from d 108 of gestation until d 5 of lactation, containing 0.00% (Control), 0.03%, 0.06%, 0.09%, 0.12%, or 0.15% of dietary nitrate. The source of nitrate used was calcium nitrate double salt. Calcium levels were kept the same among diets by using limestone. Gilts and sows were weighed and backfat was measured at arrival to the farrowing room (d 108 of gestation) and at weaning (d 27 of age). Data included number of piglets born alive, born dead, and weaned, as well as individual piglet weights at d 0, 72 h of age and weaning. Preweaning mortality was determined throughout lactation. Body weight d 0 (P = 0.04) as well as BW at 72 h of age (P < 0.01) increased linearly with increasing dosages of nitrate in the maternal diet. Litter uniformity (SD) at birth was not affected by maternal nitrate supplementation level (P > 0.10), but tended to be higher at 72 h of age in the control treatment than in all nitrate-supplemented treatments (P = 0.07), and SD decreased linearly (increased uniformity) at weaning with increasing dosages of nitrate (P = 0.05). BW at weaning (P > 0.05) and average daily gain of piglets during lactation (P > 0.05) were not affected by maternal nitrate supplementation. A tendency for a quadratic effect (P = 0.10) of the dosage of maternal dietary nitrate was found on preweaning mortality of piglets with the lowest level of mortality found at 0.09% to 0.12% of maternal nitrate supplementation. We conclude that the use of nitrate in the maternal diet of sows during the perinatal period might stimulate preweaning piglet vitality. Exact mode of action and optimal dose of nitrate still need to be elucidated.

scholarly journals Two-Generation Reproductive Toxicity Study of Resorcinol Administered Via Drinking Water to Crl:CD(SD) Rats

2008 ◽  
Vol 27 (1) ◽  
pp. 43-57 ◽  
Author(s):  
F. Welsch ◽  
M. D. Nemec ◽  
W. B. Lawrence
Keyword(s):  
Drinking Water ◽  
Adverse Effects ◽  
Case Reports ◽  
Reproductive Toxicity ◽  
Clinical Signs ◽  
Reproductive Function ◽  
Exposure Level ◽  
End Points ◽  
Sd Rats ◽  
Effect Level

The potential adverse effects of resorcinol, delivered via drinking water at 0, 120, 360, 1000, and 3000 mg/L (palatability limit), were assessed in a regulatory guideline compliant two-generation reproduction study in Crl:CD(SD) rats. Expanded end points of thyroid gland (TG) function were added because of clinical case reports indicating human TG toxicity. Average daily resorcinol intake (mg/kg) at the 3000 mg/L concentration was 233 in F0 and F1 males, whereas in females it was 304 (premating/gestation) and 660 (lactation). No resorcinol ingestion-related clinical signs of toxicity were observed. Furthermore, neither gross morphologic anomalies nor effects on reproductive function or thyroid hormone levels were detectable. Body weight reductions occurred in 3000 mg/L F0 and F1 animals and were more pronounced in males. However, there was no evidence of either cumulative toxicity in the second generation or of enhanced sensitivity to resorcinol in pregnant/lactating females. Water intake was lower in 3000 mg/L rats of both generations and intermittently, to a lesser extent, at 1000 mg/L; however, concurrent feed intake and utilization were unaffected. Decreased TG follicular colloid content (conventional histopathology; confirmed by quantitative stereomicroscopy) in the 3000 mg/L F0 males was attributed to resorcinol but not considered adverse. The 3000 mg/L intake level appeared to have caused an adaptive thyroid response to a new homeostatic level with no adverse physiological consequences in either males (the more susceptible gender) or females. There were no differences in TG histology in F0 rats of either sex at 1000 mg/L. Thus, resorcinol intake at maximum palatability via a route and mode relevant to potential human exposures via contaminated drinking water at presently unknown environmental concentrations caused no detectable adverse effects on any reproduction or TG end points. The 3000 mg/L resorcinol exposure level was the no-observed-adverse-effect level (NOAEL) for parental systemic and offspring toxicity, while 1000 mg/L was the no-observed-effect level (NOEL).

scholarly journals Dietary nitrate supplementation attenuates the reduction in exercise tolerance following blood donation

2016 ◽  
Vol 311 (6) ◽  
pp. H1520-H1529 ◽  
Author(s):  
Sinead T. J. McDonagh ◽  
Anni Vanhatalo ◽  
Jonathan Fulford ◽  
Lee J. Wylie ◽  
Stephen J. Bailey ◽  
...  
Keyword(s):  
Exercise Tolerance ◽  
Peak Power ◽  
Blood Donation ◽  
Hemoglobin Concentration ◽  
Moderate Intensity ◽  
Beetroot Juice ◽  
Moderate Intensity Exercise ◽  
Exercise Tests ◽  
Dietary Nitrate ◽  
Nitrate Supplementation

We tested the hypothesis that dietary nitrate (NO3−)-rich beetroot juice (BR) supplementation could partially offset deteriorations in O2transport and utilization and exercise tolerance after blood donation. Twenty-two healthy volunteers performed moderate-intensity and ramp incremental cycle exercise tests prior to and following withdrawal of ∼450 ml of whole blood. Before donation, all subjects consumed seven 70-ml shots of NO3−-depleted BR [placebo (PL)] in the 48 h preceding the exercise tests. During the 48 h after blood donation, subjects consumed seven shots of BR (each containing 6.2 mmol of NO3−, n = 11) or PL ( n = 11) before repeating the exercise tests. Hemoglobin concentration and hematocrit were reduced by ∼8–9% following blood donation ( P < 0.05), with no difference between the BR and PL groups. Steady-state O2uptake during moderate-intensity exercise was ∼4% lower after than before donation in the BR group ( P < 0.05) but was unchanged in the PL group. The ramp test peak power decreased from predonation (341 ± 70 and 331 ± 68 W in PL and BR, respectively) to postdonation (324 ± 69 and 322 ± 66 W in PL and BR, respectively) in both groups ( P < 0.05). However, the decrement in performance was significantly less in the BR than PL group (2.7% vs. 5.0%, P < 0.05). NO3−supplementation reduced the O2cost of moderate-intensity exercise and attenuated the decline in ramp incremental exercise performance following blood donation. These results have implications for improving functional capacity following blood loss.

Abstract P134: Preliminary Data: Dietary Nitrate Supplementation Does Not Extend Dry Static Apnea Or Wingate Performance

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Colin Carriker ◽  
Phillip Armentrout ◽  
Sarah Levine ◽  
James Smoliga
Keyword(s):  
Power Output ◽  
Preliminary Data ◽  
Repeated Measures ◽  
Peak Power ◽  
Hold Time ◽  
Wingate Test ◽  
Peak Power Output ◽  
Breath Hold ◽  
Dietary Nitrate ◽  
Nitrate Supplementation

Introduction: Previous studies have examined dietary nitrate supplementation and its effects on dry static apnea, and peak power. Dietary nitrate supplementation has been found to increase maximal apnea and peak power output. The purpose of this study was to determine the effects of beetroot juice on dry static apnea and Wingate performance. Hypothesis: Dietary nitrate will improve maximal breath hold time and peak power output. Dietary nitrate will improve tolerance to CO2, thereby improving maximal breath hold time and anaerobic capacity. Methods: In a randomized, double-blind, counterbalanced study, five healthy males (20.4±0.89 years) visited the lab on 3 separate occasions each separated by one week. Visit 1 served as a Wingate and breath hold familiarization visit. Prior to visits 2 and 3 participants were instructed to drink a beverage either a placebo (negligible nitrate content, PL) or dietary nitrate rich beverage (12.4 mmol nitrate, NIT) during the 4 days leading up to their next visit. Visits 2 and 3 consisted of two submaximal breath holds (80% of maximal determined during visit 1), with 2 minutes of rest between and three minutes of rest preceding the final breath hold for maximal duration. Finally, participants completed a standardized 10-minute warmup on the cycle ergometer before completing a 30-second maximal effort Wingate test. Results: A linear mixed effects model was used to determine whether treatment (NIT vs. PL) was associated with differences in VCO2 or PetCO2. Time (0, 10, 20, 30 min post-breath hold) and Treatment both served as repeated measures. Models were developed using multiple repeated measures covariance matrix structures, and the model with the lowest AIC was chosen as the final model. The interaction between time and treatment was included in the original models, and was removed if it was not statistically significant. Time was a statistically significant factor for VCO2 and PetCO2 (p < 0.001). Treatment, and the Time x Treatment interaction was not significant for either variable. No differences between NIT and PL were observed during the Wingate test for either time to peak power (5.02±2.45 and 6.2±2.43 sec, respectively) or maximal power (9.73±1.01 and 9.72±1.03 watts/kg, respectively) and fatigue index (49.42±14.98 and 47.30±6.99 watts/sec, respectively). Conclusion: Preliminary data indicates that in a general population four days of dietary nitrate supplementation may not improve breath hold time, tolerance to carbon dioxide in the lungs, or Wingate performance.

scholarly journals Systematic Review of Adverse Effects: A Further Step towards Modernization of Acupuncture in China

2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Junyi Wu ◽  
Yanmei Hu ◽  
Yin Zhu ◽  
Ping Yin ◽  
Gerhard Litscher ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Systematic Review ◽  
Central Nervous System ◽  
Adverse Effects ◽  
Scientific Literature ◽  
Acupuncture Treatment ◽  
Case Reports ◽  
The World ◽  
Organ Tissue

As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events in acupuncture treatment reported from 1980 to 2013 in China. All first-hand case reports of acupuncture-related complications and adverse events that could be identified in the scientific literature were reviewed and classified according to the type of complication and adverse event, circumstance of the event, and long-term patient outcome. The selected case reports were published between 1980 and 2013 in 3 databases. Relevant papers were collected and analyzed by 2 reviewers. Over the 33 years, 182 incidents were identified in 133 relevant papers. Internal organ, tissue, or nerve injury is the main complications of acupuncture especially for pneumothorax and central nervous system injury. Adverse effects also included syncope, infections, hemorrhage, allergy, burn, aphonia, hysteria, cough, thirst, fever, somnolence, and broken needles. Qualifying training of acupuncturists should be systemized and the clinical acupuncture operations should be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world.

Oral Terbinafine: A New Antifungal Agent

1997 ◽  
Vol 31 (4) ◽  
pp. 445-456 ◽  
Author(s):  
Susan M Abdel-Rahman ◽  
Milap C Nahata
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
Fungal Infections ◽  
Case Reports ◽  
Current Standard ◽  
Open Label ◽  
Double Blind ◽  
Pathogenic Yeast

Objective To review the pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of terbinafine. Available comparative data of terbinafine and other antimycotic agents are described for understanding the potential role of terbinafine in patient care. Data Sources A MEDLINE search restricted to English language during 1966–1996 and extensive review of journals was conducted to prepare this article. MeSH headings included allylamines, terbinafine, SF 86–327, dermatophytosis, dermatomycosis. Data Extraction The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open-label and controlled studies and case reports. Controlled single- or double-blind studies were evaluated to describe the efficacy of terbinafine in the treatment of various fungal infections. Data Synthesis Terbinafine is the first oral antimycotic in the allylamines class: a fungicidal agent that inhibits ergosterol synthesis at the stage of squalene epoxidation. Terbinafine demonstrates excellent in vitro activity against the majority of dermatophyte species including Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum; less activity is seen against Dematiaceae and the filamentous fungi. It is least active against the pathogenic yeast and this correlates with the relatively poor efficacy against these organisms in vivo. High concentrations of terbinafine are achieved in keratinous tissues, the site of superficial infections, and these concentrations are maintained for up to 3 months. The clinical efficacy of terbinafine against a number of dermatophyte infections exceeds that of the current standard of therapy, griseofulvin. The efficacy of terbinafine may be as good or better than that of the azole antifungals. Additional studies are required to confirm these observations. Terbinafine demonstrates a good safety profile, and relatively few drug interactions have been identified. Conclusions Terbinafine is more effective than the gold standard, griseofulvin, in the treatment of tinea pedis and tinea unguinum, with considerably shorter treatment duration in the latter. It has been proven as effective as griseofulvin in the treatment of tinea capitis, tinea corporis, and tinea cruris. Terbinafine does not appear to offer any advantage in the treatment of nondermatophyte infections; its utility in the treatment of systemic infections has yet to be established. Depending on individual institutional costs, terbinafine may be a front-line drug for some superficial infections responding poorly to the current standard of therapy.

scholarly journals An Introduction to Pharmacotherapy for Inborn Errors of Metabolism

2018 ◽  
Vol 23 (6) ◽  
pp. 432-446
Author(s):  
Aaron A. Harthan
Keyword(s):  
Adverse Effects ◽  
Inborn Errors Of Metabolism ◽  
Single Case ◽  
Case Reports ◽  
Review Article ◽  
Metabolic Process ◽  
Inborn Errors ◽  
Herbal Products ◽  
Disease States ◽  
Treatment Plans

Inborn errors of metabolism comprise a wide array of diseases and complications in the pediatric patient. The rarity of these disorders limits the ability to conduct and review robust literature regarding the disease states, mechanisms of dysfunction, treatments, and outcomes. Often, treatment plans will be based on the pathophysiology associated with the disorder and theoretical agents that may be involved in the metabolic process. Medication therapies usually consist of natural or herbal products. Established efficacious pediatric doses for these products are difficult to find in tertiary resources, and adverse effects are routinely limited to single case reports. This review article attempts to summarize some of the more common inborn errors of metabolism in a manner that is applicable to pharmacists who will provide care for these patients.

Sign in / Sign up

Export Citation Format

Share Document