ABSTRACT
The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of “other substances” in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating the addition of “other substances” to food supplements and other foods. “Other substances” are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional or physiological effect. The substance is added mainly to food supplements, but also to energy drinks and other foods. VKM has not in this series of risk assessments of “other substances” evaluated any potential beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) in food supplements, and is based on previous risk assessments and a literature search. It is emphasised that this risk assessment concerns the single fatty acids EPA, DPA or DHA separately and not mixtures of these as found in e.g. fish oil/cod liver oil. For risk assessment of combined mixtures of n-3 LCPUFAs in e.g. fish oil/cod liver oil, see the EFSA opinion from 2012 or the VKM assessment from 2011 (EFSA, 2012; VKM, 2011). In the reviewed literature of this risk assessment, no studies investigating ratios between EPA, DPA, DHA or other fatty acids in mixtures have been identified. EPA, DPA and DHA are long chain n-3 polyunsaturated fatty acids (n-3 LCPUFA) and in food these fatty acids are incorporated in triacylglycerols (TAGs) and phospholipids (PLs). Dietary sources are fatty fish, cod liver-, seal-, whale-, fish- and krill oils and human milk, containing various ratios of these fatty acids in combination. EPA can be metabolised to eicosanoids such as prostaglandins, prostacyclins and leukotrienes, all groups are biologically active substances. The eicosanoids participate in the regulation of blood pressure, renal function, blood coagulation, inflammatory and immunological reactions. DHA is an essential structural component of the brain, skin, sperm, testicles and retina. DPA can be retro-converted to EPA or converted to DHA. Still little is known of the biological effects of DPA. Humans have a limited capacity to synthesise EPA, DPA and subsequently DHA from the precursor alpha-linolenic acid (ALA), and this endogenous production is negligible in comparison to the doses used in supplementation studies. According to information from the NFSA, EPA, DPA and DHA are food supplement ingredients in Norway, and NFSA has requested a risk assessment of these fatty acids in the following doses in food supplements: EPA: 1500, 1750 and 1825 mg/day DPA: 100, 125 and 150 mg/day DHA: 1050 and 1290 mg/day Children below 10 years were not included in the terms of reference. Information about intake of EPA, DPA and DHA from the diet is scarce, but calculations performed in the Norwegian Mother and Child Cohort Study indicate a mean total intake (SD) from food and supplements of EPA around 330 (340) mg/day, DPA 43 (30) mg/day and DHA 430 (380) mg/day among pregnant women (2002 to 2008). Mean combined intake of EPA, DPA and DHA from fish oil/ cod liver oil in adults participating in a nationally representative dietary survey was 735 mg/day (VKM, 2014). The major concerns with high intake of EPA and DHA have been increased bleeding time, adverse effects related to immune function, lipid peroxidation and glucose homeostasis. EFSA concluded in 2012 that long-term supplemental intakes of 5 g/day of the n-3 LCPUFA do not raise safety concerns for adults with regard to an increased risk of spontaneous bleeding episodes or bleeding complications, or affect glucose homeostasis, immune function or lipid peroxidation. In 2011, VKM concluded that an intake n-3 LCPUFA up to 6.9 g/day was not associated with increased risk of any serious adverse events. Some adverse health effects related to gastrointestinal function, including abdominal cramps, flatulence, eructation, vomiting and diarrhea have been reported, but seem to be associated with intake of an oily substance and not related specifically to EPA, DPA and/or DHA. EPA: In the report from 2012, EFSA concluded that 1.8 g/day of supplemental EPA does not raise safety concerns in adults. None of the included studies from our literature searches limited to 2012 and onwards have investigated bleeding complications. The dosages of EPA in the three included studies in this report range from 1.8 to 3.8 g/day for 12 weeks. The main endpoints in the studies included lipid peroxidation, inflammation biomarkers of cardiovascular diseases and no serious adverse events were found related to the main endpoints. In general, adverse events were described as gastrointestinal discomforts and not related to dosage. Studies of longer duration are necessary before an intake above 1.8 g of EPA can be considered safe. The Norwegian Scientific Committee for Food Safety (VKM) concludes that the specified doses of 1500, 1750, 1825 mg/day of EPA in food supplements are unlikely to cause adverse health effects in adults (≥18 years). In 2012, EFSA did not make conclusions for children or adolescents for EPA. No new studies with EPA supplementation have been identified in children or adolescents after 2012, and therefore no risk assessment can be made for children (≥10 years) or adolescents. DPA: No dosage of DPA in food supplements can be evaluated due to lack of data. DHA: EFSA concluded that 1 g/day of supplemental DHA does not raise safety concerns for the general population (including children and adolescents). The dosages of DHA in the included trials in this report range from 1.0 to 3.6 g/day and the duration from five weeks to four years. Six out of seven studies have used dosages from 1 to 2 g DHA/day. The last study included up to 3.6 g DHA/day for four years and the age spanned from 7 to 31 years. The main endpoints in all studies included lipid peroxidation, inflammation, cognitive performance, blood pressure and biomarkers of cardiovascular diseases and no serious adverse events were found related to the main endpoints. In general, adverse events were described as gastrointestinal discomforts and not related to dosage. VKM therefore considers that the specified daily doses of DHA that moderately exceed 1 g per day (1050 and 1290 mg/day) are unlikely to cause adverse health effects in the general population including children ≥10 years and adolescents. VKM concludes that the specified doses of 1050 and 1290 mg/day of DHA in food supplements are unlikely to cause adverse health effects in the general population including children (≥10 years), adolescents and adults (≥18 years).
ABSTRACT
Objective To synthesize 18 F-DPA-714 and to study its labeling rate, radiochemical purity, stability and biological characteristics. Methods 18F-was reacted with K2CO3/K2.2.2 and then en-gaged in nucleophilic substitution with DPA-714. The crude product was purified by aluminum column and semi-preparation HPLC. The stability of 18 F-DPA-714 was identified in PBS and plasma. The lipid-water partition coefficient (LogP) was determined. Biodistribution analysis and microPET imaging were performed on mice and rats respectively. Results It took about 25 min for synthesizing 18 F-DPA-714, the radiochemi-cal yield was 31.6% (decay not corrected), and the radiochemical purity was ≥99%. The product re-mained stable within 4 h. The LogP of 18 F-DPA-714 was 2.71. Pharmacokinetics of 18 F-DPA-714 was more in line with the two compartment model, with the distribution half-life ( T1/2α) of 2.40 min and the elimina-tion half-life( T1/2β) of 69.15 min. 18 F-DPA-714 was quickly uptaken by tissues after the tail vein injection. It mainly distributed in the lungs, kidneys, and heart, with the radioactive uptake values of (17.85±7.52)%ID/g, (15.41±1.80) %ID/g and (10.56±0.94) %ID/g at 30 min post-injection, respectively. 18F-DPA-714 was mainly metabolized through the liver, and excreted by the kidneys. The uptake in bones was stable. PET dynamic scanning showed that 18 F-DPA-714 accumulated in the brain of aged rats and cleared slowly within 60 min. Conclusions 18 F-DPA-714 prepared in this study has high labeling rate, short synthesis time and small precursor dosage. It displays good biological distribution and blood-brain barrier permeability characteristics.
ABSTRACT
Objective To synthesize 18 F-DPA-714 and to study its labeling rate, radiochemical purity, stability and biological characteristics. Methods 18F-was reacted with K2CO3/K2.2.2 and then en-gaged in nucleophilic substitution with DPA-714. The crude product was purified by aluminum column and semi-preparation HPLC. The stability of 18 F-DPA-714 was identified in PBS and plasma. The lipid-water partition coefficient (LogP) was determined. Biodistribution analysis and microPET imaging were performed on mice and rats respectively. Results It took about 25 min for synthesizing 18 F-DPA-714, the radiochemi-cal yield was 31.6% (decay not corrected), and the radiochemical purity was ≥99%. The product re-mained stable within 4 h. The LogP of 18 F-DPA-714 was 2.71. Pharmacokinetics of 18 F-DPA-714 was more in line with the two compartment model, with the distribution half-life ( T1/2α) of 2.40 min and the elimina-tion half-life( T1/2β) of 69.15 min. 18 F-DPA-714 was quickly uptaken by tissues after the tail vein injection. It mainly distributed in the lungs, kidneys, and heart, with the radioactive uptake values of (17.85±7.52)%ID/g, (15.41±1.80) %ID/g and (10.56±0.94) %ID/g at 30 min post-injection, respectively. 18F-DPA-714 was mainly metabolized through the liver, and excreted by the kidneys. The uptake in bones was stable. PET dynamic scanning showed that 18 F-DPA-714 accumulated in the brain of aged rats and cleared slowly within 60 min. Conclusions 18 F-DPA-714 prepared in this study has high labeling rate, short synthesis time and small precursor dosage. It displays good biological distribution and blood-brain barrier permeability characteristics.
ABSTRACT
The aim of this study was to examine the effects of perilla oil as well as several vegetable oils, including flaxseed oil, canola oil, and rice bran oil on plasma levels of cardioprotective (n-3) polyunsaturated fatty acids in mice by feeding each vegetable oil for a period of eight weeks. Concentrations of docosapentaenoic acid (DHA) and eicosapentaenoic acid (EPA), fish-based (n-3) polyunsaturated fatty acids, showed an increase in the plasma of mice fed perilla and flaxseed oils compared to those of mice in the control group (P < 0.05), whereas rice bran and canola oils did not alter plasma DPA and EPA concentrations. Arachidonic acid concentration was increased by feeding rice bran oil (P < 0.05), but not canola, flaxseed, or perilla oil. In addition, oleic acid, linoleic acid, and docosahexaenoic acid concentrations were altered by feeding dietary rice bran, canola, perilla, and flaxseed oils. Findings of this study showed that perilla oil, similar to flaxseed oil, is cardioprotective and could be used as an alternative to fish oil or even flaxseed oil in animal models.
Subject(s)
Animals , Mice , alpha-Linolenic Acid , Arachidonic Acid , Eicosapentaenoic Acid , Fatty Acids , Fatty Acids, Monounsaturated , Fatty Acids, Unsaturated , Flax , Linoleic Acid , Linseed Oil , Models, Animal , Oils , Oleic Acid , Perilla , Plant Oils , Plasma , VegetablesABSTRACT
BACKGROUND: Since metallo-beta-lactamase (MBL)-producing isolates can hydrolyze carbapenem and also easily transfer the resistance genes to other bacteria, a rapid and accurate detection of MBL has become very important. We evaluated the utility of Mueller Hinton agar (MHA) biplate containing dipicolinic acid (DPA) as a screening method to detect IMP-1 and VIM-2 type MBL-producing isolates. METHODS: Based on our preliminary tests using various concentrations of DPA, 200 and 300 microg/mL concentration of DPA were chosen for further study. Bacterial lawns were grown on MHA biplate, one half of which contained DPA while the other did not. The inhibition zone around the imipenem (IPM) disk on both sides of this plate was compared. The stability of DPA in the stored DPA-MHA biplate was also evaluated during three months using two MBL- and one non-MBL-producing isolates. RESULTS: When the criterion of a > or =7 mm increase of inhibition zone around the IPM disk on the MHA containing DPA compared to MHA without DPA was used, the sensitivities and specificities were 94.7% and 97.6% for 200 microg/mL DPA-MHA biplate, and 98.2% and 97.6% for 300 microg/mL DPA-MHA biplate, respectively. The activity of the DPA in this biplate was stable for three months. CONCLUSIONS: Assays using DPA 300-MHA biplate were highly sensitive and specific for the detection of IMP-1 and VIM-2 type MBL-producing bacteria. In addition, it is easy to perform; so, it may be useful to apply this method for detection of IMP-1 and VIM-2 type MBL in clinical laboratories.
Subject(s)
Agar , Anti-Bacterial Agents/pharmacology , Bacteriological Techniques , Chelating Agents/chemistry , Drug Resistance, Bacterial , Gram-Negative Bacteria/drug effects , Imipenem/pharmacology , Picolinic Acids/chemistry , Reagent Kits, Diagnostic , Sensitivity and Specificity , beta-Lactamases/analysisABSTRACT
Introdução: A palavra pica é definida como o desejo intenso e persistente da ingestão de itens não-alimentares com pouco ou nenhum valor nutricional.Pacientes em diálise podem estar propensos a tal distúrbio. Objetivo: Investigar a prevalência de pica em pacientes em diálise peritoneal. Métodos:Através de entrevista e aplicação de questionário, foram avaliados 106 pacientes maiores de 20 anos, submetidos à diálise peritoneal ambulatorial contínua(DPAC) ou à diálise peritoneal automatizada (DPA). Nos pacientes que apresentavam pica, foram coletados exames bioquímicos, incluindo: albumina,cálcio, creatinina, ferritina, ferro, fósforo, glicemia, hematócrito, hemoglobina, potássio, transferrina e uréia séricos, além do Kt/V para determinação da adequação dialítica. Os pacientes tiveram peso e estatura medidos, para cálculo do índice de massa corporal (IMC). Resultados: A idade dos pacientes foi de 57,1±14,3 anos (média±DP). Observou-se que 32% (n=34) dos indivíduos entrevistados apresentavam pica. Destes, a maioria dos praticantes(76,5%, n=26) era do sexo feminino. Os itens ingeridos em maior prevalência foram: gelo (25%), vinagre (20,8%) e suco de limão puros (12,5%). Não houvediferença significativa na presença de pica entre obesos e não obesos, assim como o problema não foi associado à anemia, sobrepeso ou à inadequacidade dialítica. Conclusão: A ingestão de itens não-alimentares não é um achado incomum na população em diálise peritoneal.
Introduction: The word pica is defined as an intensive and persistent desire for the intake of non-food items with little or no nutritional value. Dialysis patientsmay be susceptible to such disturbance. Objective: To investigate the prevalence of pica in a population of peritoneal dialysis patients. Methods: An openinterview and a questionnaire were applied to 106 patients in continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD).Patients younger than 20 years were excluded from the study. For those patients who presented pica, biochemical analysis was performed, which included the serum measurements of albumin, calcium, creatinine, ferritin, iron, phosphorus, glucose, hematocrit, hemoglobin, potassium, transferrin and urea. Moreover, the delivery dose of dialysis was assessed by the calculation of Kt/V. Also, the body mass index (BMI) was calculated using measured weight and height. Results: The pica practice was observed in 32% (n=34) of the PD patients, whose age was 57.1±14.3 years (mean ±SD). From these patients, the majority of pica practitioners (76.5%, n=26) was female. The most reported consumed items were: ice (25%), pure vinegar (20.8%) and lemon juice(12.5%). There was no significant difference in the presence of pica between obese and non-obese patients, and the problem was not associated w i t h anemia, overweight or dialysis inadequacy. Conclusion: The intake of non-food items is not an uncommon finding in the peritoneal dialysis population.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged, 80 and over , Peritoneal Dialysis , Pica/complications , Pica/diagnosis , Pica/metabolismABSTRACT
No abstract available.
Subject(s)
Humans , Infant, Newborn , Absorptiometry, Photon , Bone DensityABSTRACT
In previous papers, we experimentally demonstrated the enhancing effect of D-phenylalanine (DPA) administration on the analgesic effect of acupuncture by the increase of pain threshold. In the present study, we examined the effect of administration manners in the patients with chronic lumbago who visited our anaesthesiological department. We conducted a double-blind study with two different administration manners: “previous-day” and “just-before”.<br>METHODS<br>Fifty-six patients suffering from chronic low back pain for more than three months were devided into two groups. DPA or placebo was orally administered intwo different manners prior to low-frequency electro-acupuncture treatment. Group I patients (26 cases), took 0.5g three times (i. e. a total of 1.5g): after the evening meal and before go to bed on the day before, and after the beakfast on the day of acupuncture (“previous-day” administration). Group II patients (30 cases), took 4.5g 30 minutes before acupuncture treatment “just-before” administration. The treatment was undertaken twice with DPA administration and twice with placebo administration for each group. “Direct effect” was determined by the number scale method and a comparison between the two groups was made. In the additional experiment, three volunteers were orally given 4.0g or 1.5g DPA, and blood phenylalanine level was determined two hours, four hours and one month later.<br>RESULTS<br>In the group I (previous-day administration), “DPA+acupuncture” produced the following result: excellent 7.8%, good 69.2%, moderate 19.2%, (significantly different from placebo administration). In the group II (just-before administration), “DPA+acupuncture” produced the following result: excellent 23%, good 37%, moderate 20%, and no-effect 20% (significantly different from placebo administration). Comparing group I with group II, the percentage of the “excellent” or “good” cases in the former was larger than that of the latter (+17%). Blood phenylalanine level showed its high value 2-4 hours after administration of 4g DPA, whereas 2 hours after that of 1.5g DPA.<br>Conducting a clinical investigation into the effectual administration (timing and doses) of DPA, we found that previous-day administration is more effective than “just-before” administration in enhancing effect of acupuncture analgesia. Although there is room for further studies with a larger number of cases, considering that DPA has a “slow onset long acting” effect (Ehrenpreis), we can conclude that the series administration of DPA on the day before acupuncture treatment is advisable.
ABSTRACT
Dipicolinic acid synthesis in Penicillium citreoviride strain 3114 was inhibited by Ca2+ ions, but not by Ba2+, Cu2+or Fe2+. Among the metals tested, only Zn2+ inhibited the synthesis of dipicolinic acid and promoted sporulation. None of these metals reversed the inhibition by Ca2+ or Zn2+ . Α mutant 27133-dpa-ca selected for resistance to feedback inhibition by dipicolinic acid: Ca2+ complex showed cross-resistance to inhibition by dipicolinic acid: Zn2+. Both 3114 and 27133-dpa-ca excreted a number of aliphatic and amino acids during secondary metabolism of dipicolinic acid. In the presence of 1000 ppm of Ca2+, accumulation of citric acid and α-aminoadipic acid was completely inhibited under conditions of inhibition of dipicolinic acid in parent strain 3114 but not in the mutant. Citric acid with or without Ca2+ did not inhibit the de novo synthesis of dipicolinic acid in the strain 3114. In fact, citric acid in the presence of Ca2+ improved significantly rate of dipicolinic acid synthesis. Apart from resistance to feed back inhibition by dipicolinic acid: Ca2+ complex, mutant differed from the parent in three other aspects viz. (i) dipicolinic acid synthesis was not subject to catabolite repression by glucose, (ii) sporulation as well as dipicolinic acid synthesis was dependent on the presence of Ca2+ ions in the medium and (iii) Mg2+ requirement for the mutant increased three fold. Higher requirement of the Mg2+ could be partially relieved by Ca2+ during secondary metabolism. The results support the inference that de novo synthesis of dipicolinic acid is regulated through feedback inhibition by dipicolinic acid: Ca2+ complex.
ABSTRACT
Synthesis of dipicolinic acid in Penicillium citreoviride showed typical kinetics of a secondary metabolite. Its synthesis resumed during idiophase and continued through stationary phase of growth. Total duration of synthesis was 100 h at the end of which its synthesis was arrested. Production of dipicolinic acid by the cells was subject to catabolite repression by glucose and was not subject to end product inhibition by exogenously added dipicolinic acid. Unlike the bacteria, dipicolinic acid synthesis in this mold was highly sensitive to inhibition by calcium ions in the growth medium. Calcium promoted sporulation but dipicolinic acid was not found to be present in detectable amounts in mold spores. Addition of dipicolinic acid and Ca2+ completely inhibited its de novo synthesis, an effect not observed when calcium was replaced by Mg2+ When the mold was grown in the presence of calcium alone, its inhibitory effects on de novo synthesis of dipicolinic acid were expressed only after some of this metabolite was first synthesised by the producer cells suggesting that the active feedback inhibitor is probably a Ca: dipicolinic acid complex. It is suggested that over-production of this metabolite is very important to the mold in increasing its survival potential in nature by retrieving the essential minerals from the environment through ligand: metal complex at a time when cells are in the process of dying, so that a proper mineral balance is maintained within the cells.