RESUMEN
Objective: To determine the pharmacokinetics (PK) of two oral doses of a Cannabis herbal extract (CHE) containing 1:20 THC:CBD in 12 healthy Domestic Shorthair cats. Methods: Single-dose PK were assessed after oral administration of CHE at low or high dose (2 mg CBD + 0.1 mg THC, or 5 mg CBD + 0.25 mg THC per kg bw, respectively; n = 6 per group) in fasting cats. Blood samples were drawn up to 48 h following CHE administration. Plasma samples were analyzed for CBD, THC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH using a previously validated LC-MS/MS method. Results: CBD and THC were quickly absorbed (mean Tmax of 2.4-2.9 h). Maximum plasma concentrations (Cmax) ranged from 36-511 ng/mL and 6.8-61 ng/mL for CBD and THC, respectively. Elimination was initially rapid for both CBD and THC, though a prolonged elimination phase was noted for CBD in some cats (T1/2 λ up to 26 h). Dose-adjusted Cmax and AUC0-last values were not statistically significantly different (p > 0.05) between dose groups indicating CBD and THC concentrations increased in a manner proportional (linear) to the dose. Dose-adjusted THC Cmax and AUC0-last were significantly higher than the corresponding dose-adjusted CBD parameters (p < 0.01). Low concentrations of the metabolite 6-OH-CBD were quantified but metabolites 7-OH-CBD, 11-OH-THC, and THC-COOH were not detected in any plasma samples. Inter-individual variance was notable. Salivation shortly after dosing was observed in two cats in the high dose group; these animals had substantially lower cannabinoid concentrations than other cats in this group. No adverse clinical signs (including vomiting, change in mentation or other neurological signs) were noted. Clinical significance: Although cats did not display adverse effects after administration of a single oral dose of 1:20 THC:CBD CHE formulation at 2 or 5 mg CBD/kg bw, observed plasma concentrations were highly variable but generally lower than in dogs receiving the same dose and formulation. Administration of CHE in the fasting state may not optimize CBD absorption, and oral dosing may be challenging when administering an oil-based CHE in some cats.
RESUMEN
Attention deficit hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder that is highly prevalent in children and adults. An increasing number of patients with ADHD are self-medicating with cannabis, despite a lack of evidence on efficacy and safety. This case report describes 3 males (ages 18, 22, and 23) who have integrated cannabis into their treatment regimen with positive results. Semistructured interviews conducted with the patients describe subjective improvements in symptoms and on quality of life. Improvements on validated rating scales conducted post-cannabis initiation, compared to pre-cannabis initiation obtained from the medical chart, corroborated their personal accounts. Scores on the PHQ-9 (measuring depression) improved by 8-22 points (30-81%), and the SCARED (measuring anxiety) ranged from 0 to 27 points (up to 33%). Improvements on the CEER-9 scale (measuring regulation) ranged from 2 to 7 points (22-78%), and the 9-item SNAP scale (measuring inattention) showed improvements of 2-8 points (7-30%). Mild adverse events including short-term memory problems, dry mouth, and sleepiness were reported. Blood samples were also collected from the patients to determine the plasma concentrations of the cannabinoids and relevant metabolites before and after a cannabis administration. After cannabis use, the plasma levels for CBD and THC ranged from 0 to 15.29 ng/mL and 1.32 to 13.76 ng/mL, respectively. Cannabinoids, however, were not detected prior to dosing, suggesting that cannabis played a complimentary role in the therapeutic regimen of these 3 patients. Clinical trials are recommended to confirm the efficacy of cannabis in the treatment of ADHD.
RESUMEN
Objective: To determine the pharmacokinetics (PK) and safety of various oral doses of a Cannabis herbal extract (CHE) containing a 1:20 ratio of Δ9-tetrahydrocannabinol (THC):cannabidiol (CBD) in 13 healthy Beagle-cross dogs. Methods: Single-dose PK was assessed after oral administration of CHE at low, medium, or high doses [2, 5, or 10 mg CBD and 0.1, 0.25, or 0.5 mg THC per kg of body weight (bw), respectively; n = 6 per group]. Dogs were monitored for adverse events for up to 48 h post-dose. Evaluations of neurological signs, clinical laboratory abnormalities, and other adverse events were performed in two separate study phases: a multiple-dose phase with 12 dogs receiving five medium doses (5 mg CBD/kg bw) at 12 h intervals, and a single low-dose (2 mg CBD/kg bw), randomized, blinded, negative controlled study with 13 dogs. Results: Cannabinoids CBD, THC, CBC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH were quantified in plasma. CBD and THC were rapidly absorbed (mean T max of 1.9-2.3 h) and initially depleted rapidly (mean CBD T 1/2ß of 2.3-2.6 h). A prolonged elimination phase (mean CBD T 1/2λ of 13.3-24.4 h) was observed. CBD and THC concentrations increased in a dose-dependent (non-linear) manner, with disproportionally greater cannabinoid exposure relative to the dose increase. Neurological signs (hyperesthesia or proprioceptive deficits) were noted in five of six dogs in the high-dose group, but only occasionally or rarely in the medium- and low-dose groups, respectively. Presence and severity of clinical signs correlated with plasma cannabinoid concentrations. Dogs appeared to develop a tolerance to cannabinoid effects after multiple CHE doses, with fewer neurological signs noted after the final (fifth) vs. first dose. No clinically meaningful changes in blood count or chemistry values occurred after multiple CHE doses. Clinical Significance: Dogs tolerated the 1:20 THC:CBD formulation well at low and medium doses, but clinically meaningful neurological signs were observed at high doses. Because of non-proportional increases in plasma cannabinoid concentrations with increasing doses, as well as potential differences in CHE product composition and bioavailability, the possibility of adverse events and dose regimen consistency should be discussed with dog owners.
RESUMEN
Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study. Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 Δ9-tetrahydrocannabinol (THC): CBD up to 10-12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms, and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css, Min) of selected cannabinoids were quantified. Results: All seven participants tolerated the CHE up to 10-12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. CSS, Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. CSS, Min CBD levels associated with a >50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, CSS, Min levels of THC remained lower than what would be expected to cause intoxication. Conclusion: The preliminary data suggest an initial CBD target dose of 5-6 mg/kg/day when a 1:20 THC:CBD CHE is used. Possible non-linear pharmacokinetics of CBD and CBC needs investigation. The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day.
RESUMEN
The plant Cannabis sativa produces over 140 known cannabinoids. These chemicals generate considerable interest in the medical research community for their possible application to several intractable disease conditions. Recent reports have prompted parents to strongly consider Cannabis products to treat their children with drug resistant epilepsy. Physicians, though, are reluctant to prescribe Cannabis products due to confusion about their regulatory status and limited clinical data supporting their use. We provide the general paediatrician with a brief review of cannabinoid biology, the literature regarding their use in children with drug resistant epilepsy, the current Health Canada and Canadian Paediatric Society recommendations and also the regulations from the physician regulatory bodies for each province and territory. Given the complexities of conducting research on Cannabis products for children with epilepsy, we also discuss outstanding research objectives that must be addressed to support Cannabis products as an accepted treatment option for children with refractory epilepsy.
RESUMEN
We performed a scoping review on sought-after complementary therapies for patients with inflammatory bowel disease (IBD), specifically diet, physical activity and exercise (PA/E), and psychotherapy. We aim to update patients with IBD on therapies for self-care and provide physicians with guidance on how to direct their patients for the management of IBD. A search of MEDLINE, EMBASE, and PUBMED was completed in Sept 2016. Studies on diet, PA/E, or psychotherapy in patients with IBD were included. Medical Subject Heading terms and Boolean operators were used. The search was limited to full-text English articles describing an adult population. This review included 67 studies: Diet (n = 19); PA/E (n = 19); and psychotherapy (n = 29). We have made the following recommendations: (1) Diet: Consumption of diets rich in vegetables, fruit and soluble fiber may be beneficial in IBD. A trial of a low FODMAP diet can be considered in those patients with functional gastrointestinal symptoms. Restrictive diets are lacking in evidence and should be avoided; (2) PA/E: Regular low-moderate intensity activity, including cardiovascular and resistance exercise, has been shown to improve quality of life (QOL) and may improve inflammation; and (3) psychotherapy: Therapies such as cognitive-behavioural interventions, mindfulness, hypnosis, and stress management have been shown to improve QOL, but evidence is limited on their impact on anxiety, depression, and disease activity. Overall, these complementary therapies are promising and should be used to treat patients with IBD from a more holistic perspective.
Asunto(s)
Terapias Complementarias/métodos , Fibras de la Dieta/uso terapéutico , Enfermedades Inflamatorias del Intestino/terapia , Autocuidado/métodos , Terapias Complementarias/normas , Gastroenterología/métodos , Gastroenterología/normas , Humanos , Modalidades de Fisioterapia/normas , Guías de Práctica Clínica como Asunto , Psicoterapia/métodos , Psicoterapia/normas , Calidad de VidaRESUMEN
BACKGROUND: Initial studies suggest pharmaceutical grade cannabidiol (CBD) can reduce the frequency of convulsive seizures and lead to improvements in quality of life in children affected by epileptic encephalopathies. With limited access to pharmaceutical CBD, Cannabis extracts in oil are becoming increasingly available. Physicians show reluctance to recommend Cannabis extracts given the lack of high quality safety data especially regarding the potential for harm caused by other cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC). The primary aims of the study presented in this protocol are (i) To determine whether CBD enriched Cannabis extract is safe and well-tolerated for pediatric patients with refractory epilepsy, (ii) To monitor the effects of CBD-enriched Cannabis extract on the frequency and duration of seizure types and on quality of life. METHODS: Twenty-eight children with treatment resistant epileptic encephalopathy ranging in age from 1 to 10 years will be recruited in four Canadian cities into an open-label, dose-escalation phase 1 trial. The primary objectives for the study are (i) To determine if the CBD-enriched Cannabis herbal extract is safe and well-tolerated for pediatric patients with treatment resistant epileptic encephalopathy and (ii) To determine the effect of CBD-enriched Cannabis herbal extract on the frequency and duration of seizures. Secondary objectives include (i) To determine if CBD-enriched Cannabis herbal extracts alter steady-state levels of co-administered anticonvulsant medications. (ii) To assess the relation between dose escalation and quality of life measures, (iii) To determine the relation between dose escalation and steady state trough levels of bioactive cannabinoids. (iv) To determine the relation between dose escalation and incidence of adverse effects. DISCUSSION: This paper describes the study design of a phase 1 trial of CBD-enriched Cannabis herbal extract in children with treatment-resistant epileptic encephalopathy. This study will provide the first high quality analysis of safety of CBD-enriched Cannabis herbal extract in pediatric patients in relation to dosage and pharmacokinetics of the active cannabinoids. TRIAL REGISTRATION: http://clinicaltrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2016 Dec 16. Identifier NCT03024827, Cannabidiol in Children with Refractory Epileptic Encephalopathy: CARE-E; 2017 Jan 19 [cited 2017 Oct]; Available from: http://clinicaltrials.gov/ct2/show/NCT03024827.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Cannabidiol/administración & dosificación , Epilepsia Refractaria/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/farmacocinética , Cannabidiol/efectos adversos , Cannabidiol/farmacocinética , Niño , Preescolar , Epilepsia Refractaria/sangre , Quimioterapia Combinada , Humanos , Lactante , Extractos Vegetales/efectos adversos , Extractos Vegetales/farmacocinética , Calidad de VidaRESUMEN
Systemic cytotoxic chemotherapy remains the mainstay of metastatic breast cancer; however, prognosis and overall survival is unfavorable due to inadequate treatment response and/or unacceptable toxicity. Natural compounds and their active metabolites receive increasing attention as possible adjuvant therapy with cancer chemotherapeutics to improve treatment response, survival rates, and quality of life of breast cancer patients. This study investigated the combination of flaxseed lignans (Secoisolariciresinol and Enterolactone) with classic chemotherapeutic agents (Docetaxel, Doxorubicin, and Carboplatin) with different mechanisms of action to determine whether flaxseed lignans could enhance the cytotoxic effect of such drugs in the metastatic breast cancer cell lines, SKBR3 and MDA-MB-231. The experimental data suggests that flaxseed lignans significantly enhanced the ability of chemotherapeutic agents to cause cytotoxicity in SKBR3 and MDA-MB-231 breast cancer cells. A three compound combination study found that enterolactone and metformin together in combination with relatively low concentrations of chemotherapeutic drugs were able to significantly decrease cancer cell viability, compared to low concentrations of the individual chemotherapeutic drug alone. Our in vitro evaluation suggests a future direction in improving chemotherapeutic efficacy in breast cancer by adjuvant therapy with the flaxseed lignans.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Lino/química , Lignanos/farmacología , 4-Butirolactona/administración & dosificación , 4-Butirolactona/análogos & derivados , Neoplasias de la Mama/patología , Butileno Glicoles/administración & dosificación , Carboplatino/administración & dosificación , Línea Celular Tumoral , Suplementos Dietéticos , Docetaxel/administración & dosificación , Doxorrubicina/administración & dosificación , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Concentración 50 Inhibidora , Lignanos/administración & dosificación , Metformina/administración & dosificaciónRESUMEN
Evidence from the literature suggests that dietary flaxseed lignans have the ability to modulate inflammation, which is recognized as the underlying basis of multiple chronic human diseases in older adults. Our objective was to determine the effects of oral lignan supplementation on biochemical and functional indicators of inflammation as well as safety and tolerability in older healthy adults. We designed a randomized, double-blind, placebo-controlled clinical trial in older healthy adults (60-80 years) to assess flaxseed lignan-enriched complex (â¼38% secoisolariciresinol diglucoside [SDG]; 600 mg SDG dose) oral supplementation effects on biochemical and functional indicators of inflammation and safety and tolerability in older healthy adults after 6 months of once-daily oral administration. The clinical trial confirmed that plasma concentration of total flaxseed lignans (free and conjugated forms) secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (ENL) were significantly associated with daily oral supplementation of flaxseed lignan-enriched complex (p < 0.05). A significant decrease in systolic blood pressure (SBP; from a mean of 155 ± 13 mm Hg at baseline to 140 ± 11 mm Hg at 24 weeks) was observed in lignan-supplemented participants stratified into an SBP ≥140 mm Hg subcategory (p = 0.04). No differences were found between treatment or placebo groups in terms of cognition, pain, activity, physical measurements (calf, waist, and upper arm circumstances), and grip strength. With respect to blood inflammatory markers, lipid profiles, and biochemical parameters, no significant differences were found between treatment and placebo groups at the end of the 6-month supplementation. No adverse effects were reported during supplementation. These data further support the safety and tolerability of long-term flaxseed lignan-enriched complex supplementation in older adults and identify an ability to favorably modulate SBP, an important risk factor in cardiovascular disease.
Asunto(s)
Suplementos Dietéticos , Lino/química , Inflamación/terapia , Lignanos/farmacología , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Presión Sanguínea/efectos de los fármacos , Butileno Glicoles/farmacología , Dieta , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Glucósidos/farmacología , Humanos , Persona de Mediana Edad , Proyectos Piloto , Resultado del TratamientoRESUMEN
BACKGROUND: Increased oxidative stress and inflammation are associated with aging, and contribute to an increased risk of chronic disease in older adults. Flaxseed lignans demonstrate antioxidant and anti-inflammatory activity, but their ability to reduce oxidative stress and inflammation markers in older adult populations has received limited investigation. OBJECTIVE: This is a chronic intervention trial of community-dwelling healthy older adults to examine the effects of a flaxseed lignan (secoisolariciresinol diglucoside; SDG) enriched supplement (BeneFlax) compared to a placebo. The primary aim was to demonstrate the safety of BeneFlax and confirm its anti-inflammatory efficacy on markers of oxidative stress and inflammation, and subsequent functional outcomes, including those associated with its anti-inflammatory efficacy. A secondary aim was to determine flaxseed lignan metabolite concentrations in blood. METHODS: A double-blind randomized clinical trial was conducted. Subjects were healthy community-dwelling adults aged 60-80 years. Testing was performed at baseline, 8, 16, and 24 weeks. The 24-week intervention consisted of 600 milligrams (mg) of SDG daily or an equivalent amount (volume) of placebo. All participants received 1000 international units of vitamin D to ensure adequate vitamin D status. Measurements consisted of blood pressure, hematology, and tolerability for safety assessments; blood oxidative stress and inflammatory biomarkers for efficacy; and cognition, muscle strength, and pain as functional outcomes. Secondary endpoints of plasma levels of lignan metabolites were analyzed by mass spectrometry. Other tests, such as bone turnover markers and fecal levels of flax cyclolinopeptides, will be performed at a later date. RESULTS: Thirty-two participants were recruited (19 intervention and 13 control) and all completed the trial. Numerous Health Canada-imposed exclusion criteria limited recruitment success. Analyses are ongoing, but the baseline data available for a number of parameters indicate no differences between treatment groups. Safety measures (vital signs) did not change from baseline and were not significantly different between treatment and placebo groups at 24 weeks. CONCLUSIONS: Preliminary results indicate that no safety concerns are associated with administering 600 mg SDG for 24 weeks to adults between the ages of 60 and 80 years. TRIAL REGISTRATION: Clinicaltrials.gov NCT01846117; https://clinicaltrials.gov/ct2/show/NCT01846117 (Archived by WebCite at http://www.webcitation.org/6nlDZNjmA).
RESUMEN
Consumption of flaxseed lignans is associated with various health benefits; however, little is known about the bioavailability of purified lignans in flaxseed. Data on their bioavailability and hence pharmacokinetics (PK) are necessary to better understand their role in putative health benefits. In the present study, we conducted a comparative PK analysis of the principal lignan of flaxseed, secoisolariciresinol diglucoside (SDG), and its primary metabolites, secoisolariciresinol (SECO), enterodiol (ED) and enterolactone (EL) in rats. Purified lignans were intravenously or orally administered to each male Wistar rat. SDG and its primary metabolites SECO, ED and EL were administered orally at doses of 40, 40, 10 and 10 mg/kg, respectively, and intravenously at doses of 20, 20, 5 and 1 mg/kg, respectively. Blood samples were collected at 0 (pre-dose), 5, 10, 15, 20, 30 and 45 min, and at 1, 2, 4, 6, 8, 12 and 24 h post-dosing, and serum samples were analysed. PK parameters and oral bioavailability of purified lignans were determined by non-compartmental methods. In general, administration of the flaxseed lignans SDG, SECO and ED demonstrated a high systemic clearance, a large volume of distribution and short half-lives, whereas administration of EL at the doses of 1 mg/kg (intravenously) and 10 mg/kg (orally administered) killed the rats within a few hours of dosing, precluding a PK analysis of this lignan. PK parameters of flaxseed lignans exhibited the following order: systemic clearance, SDG < SECO < ED; volume of distribution, SDG < SECO < ED; half-life, SDG < ED < SECO. The percentage of oral bioavailability was 0, 25 and < 1 % for SDG, SECO and ED, respectively.
Asunto(s)
Estrógenos/metabolismo , Lino/química , Lignanos/metabolismo , Fitoestrógenos/metabolismo , Semillas/química , 4-Butirolactona/administración & dosificación , 4-Butirolactona/efectos adversos , 4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , 4-Butirolactona/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Butileno Glicoles/administración & dosificación , Butileno Glicoles/efectos adversos , Butileno Glicoles/metabolismo , Butileno Glicoles/farmacocinética , Suplementos Dietéticos/efectos adversos , Relación Dosis-Respuesta a Droga , Estrógenos/administración & dosificación , Estrógenos/efectos adversos , Estrógenos/farmacocinética , Glucósidos/administración & dosificación , Glucósidos/efectos adversos , Glucósidos/metabolismo , Glucósidos/farmacocinética , Semivida , Inyecciones Intravenosas , Absorción Intestinal , Cinética , Lignanos/administración & dosificación , Lignanos/efectos adversos , Lignanos/farmacocinética , Masculino , Tasa de Depuración Metabólica , Fitoestrógenos/administración & dosificación , Fitoestrógenos/efectos adversos , Fitoestrógenos/farmacocinética , Distribución Aleatoria , Ratas WistarRESUMEN
CONTEXT: The natural health product, BeneFlax, is a standardized flaxseed [Linum usitatissimum L. (Linaceae)] lignan enriched product with evidence of product quality and known quantity of the bioactive component, lignan. The acceptance of this natural health product for its various health benefits requires greater evidence of its safety in the general population. OBJECTIVE: We determined whether flaxseed lignan causes clinical hypoglycemia or hypotension in healthy older adults as an important aspect of safety. MATERIALS AND METHODS: Participants aged 49-87 years were randomized in a double-blind trial to receive flaxseed lignan (543 mg/day in BeneFlax) or placebo while completing a 6-month walking program. The 94 participants who completed the study were stratified by age (<65 years versus ≥65 years) and treatment category to determine whether older adults were more susceptible to adverse effects. RESULTS: After 6 months of treatment, average plasma glucose level (5.4 ± 0.6 mmol/L), systolic blood pressure (127 ± 14 mm Hg), and diastolic blood pressure (80 ± 9 mm Hg) were within normal clinical range. Controlling for sex and body mass index covariates resulted in no observed differences between plasma glucose or blood pressure measurements between treatment or age groups (p > 0.05). No incidents of hypoglycemia or hypotension were observed during BeneFlax treatment, suggesting that 543 mg falls at or below the no observable adverse effect level (NOAEL). DISCUSSION AND CONCLUSION: These data suggest the flaxseed lignan product BeneFlax does not pose a risk of hypoglycemia or hypotension in healthy adults aged 49-87 years.
Asunto(s)
Suplementos Dietéticos/efectos adversos , Lino/efectos adversos , Lignanos/efectos adversos , Factores de Edad , Anciano , Anciano de 80 o más Años , Glucemia/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Femenino , Humanos , Hipoglucemia/epidemiología , Hipotensión/epidemiología , Lignanos/administración & dosificación , Masculino , Persona de Mediana Edad , Nivel sin Efectos Adversos ObservadosRESUMEN
Elk velvet antler (EVA) has a traditional use for promotion of general health. However, evidence of EVA effects at different lifestages is generally lacking. This paper investigated the effects of long-term maternal dietary EVA supplementation on physical, reflexological and neurological development of rat offspring. Female Wistar rats were fed standard chow or chow containing 10% EVA for 90 days prior to mating and throughout pregnancy and lactation. In each dietary group, 56 male and 56 female pups were assessed for physical, neuromotor, and reflexologic development postnatally. Among the examined physical developmental parameters, incisor eruption occurred one day earlier in pups nursing dams receiving EVA. Among neuromotor developmental parameters, duration of supported and unsupported standing was longer for pups nursing EVA supplemented dams. Acquisition of neurological reflex parameters (righting reflex, negative geotaxis, cliff avoidance acoustic startle) occurred earlier in pups nursing dams receiving EVA. Longterm maternal EVA supplementation prior to and during pregnancy and lactation accelerated certain physical, reflexologic, and neuromotor developmental milestones and caused no discernible adverse effects on developing offspring. The potential benefits of maternal EVA supplementation on postnatal development warrants further investigation to determine whether EVA can be endorsed for the promotion of maternal and child health.
RESUMEN
Vitamin-mineral supplementation may offer older adults health and cognition-related benefits but overuse may contribute to polypharmacy. We examined the prevalence of supplement usage in long-term care facility (LTC) residents (≥ 65 years of age). As cognition may be affected by nutrition, we also examined use in those with diagnosis of dementia and those with no dementia diagnosis. The prevalence of supplement usage and overall "pill count" from pharmaceutical use was assessed in 189 LTC residents and a subsample of 56 older adults with dementia diagnosis, respectively. Participants were residing in an LTC facility of a mid-size metropolitan area during 2009. The average use of supplements was 1.0 per day for all residents, with 35% taking vitamin D supplements, 20% multivitamins, and 26% calcium. Supplement use was similar (p ≥ 0.05) for those with dementia diagnosis (53%, average 2.0 per day) and for those without such diagnosis (45%, average 2.2 per day). Usage ranged between 1-6 supplements per day. In both of these groups, â¼73% of users were taking vitamin D. The number of prescribed medications ranged from 4 to 24 (average 10.2) in a subsample of residents whose supplement intake was 0 to 6 (average 2). These findings suggest an overall low rate of supplement use, with no significant differences (p ≥ 0.05) in use between residents with and without dementia diagnosis. However, some residents were at risk for supplement overuse.
Asunto(s)
Demencia/tratamiento farmacológico , Suplementos Dietéticos , Servicios de Salud para Ancianos , Hogares para Ancianos , Cuidados a Largo Plazo , Casas de Salud , Pautas de la Práctica en Medicina , Vitaminas/uso terapéutico , Anciano , Distribución de Chi-Cuadrado , Estudios Transversales , Suplementos Dietéticos/efectos adversos , Revisión de la Utilización de Medicamentos , Femenino , Adhesión a Directriz , Servicios de Salud para Ancianos/estadística & datos numéricos , Hogares para Ancianos/estadística & datos numéricos , Humanos , Cuidados a Largo Plazo/estadística & datos numéricos , Masculino , Casas de Salud/estadística & datos numéricos , Polifarmacia , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Medicamentos bajo Prescripción/uso terapéutico , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Vitaminas/efectos adversosRESUMEN
We report a rapid and simple HPLC method with fluorescence detection for the quantification of the major flaxseed lignan, secoisolarisiresinol diglucoside (SDG) and its major metabolites. The method is specific for SDG, secoisolarisiresinol (SECO), enterodiol (ED) and entrolactone (EL) in rat serum. The assay procedure involves chromatographic separation using a Waters Symmetry C(18) reversed-phase column (4.6 mm x 150 mm, 5 µm) and mobile phase gradient conditions consisting of acetonitrile (0.1% formic acid) and water (0.1% formic acid). SDG extraction from serum requires the use of Centrifuge filters while SECO, ED and EL are extracted with diethyl ether. The organic layer is evaporated and reconstituted in 100 µL of mobile phase and 50 µL of reconstituted sample or filtrate is injected onto the column. Total run time is 25 min. Calibration curves are linear (r² ≥ 0.997) from 0.05 to 10 µg/mL for SDG and EL and 0.01-10 µg/mL for SECO and ED. Precision and accuracy are within USFDA specified limits. The stability of all lignans is established in auto-injector, bench-top, freeze-thaw and long-term stability at -80 °C for 30 days. The method's reasonable sensitivity and reliance on more widely available HPLC technology should allow for its straightforward application to pharmacokinetic evaluations of lignans in animal model systems such as the rat.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Lino/química , Lignanos/análisis , Extractos Vegetales/análisis , Animales , Cromatografía Líquida de Alta Presión/instrumentación , Fluorescencia , Lignanos/sangre , Lignanos/farmacocinética , Masculino , Extractos Vegetales/sangre , Extractos Vegetales/farmacocinética , Ratas , Ratas WistarRESUMEN
Flaxseed is the richest source of the lignan secoisolariciresinol diglucoside (SDG). After ingestion, SDG is converted to secoisolariciresinol, which is further metabolised to the mammalian lignans enterodiol and enterolactone. A growing body of evidence suggests that SDG metabolites may provide health benefits due to their weak oestrogenic or anti-oestrogenic effects, antioxidant activity, ability to induce phase 2 proteins and/or inhibit the activity of certain enzymes, or by mechanisms yet unidentified. Human and animal studies identify the benefits of SDG consumption. SDG metabolites may protect against CVD and the metabolic syndrome by reducing lipid and glucose concentrations, lowering blood pressure, and decreasing oxidative stress and inflammation. Flax lignans may also reduce cancer risk by preventing pre-cancerous cellular changes and by reducing angiogenesis and metastasis. Thus, dietary SDG has the potential to decrease the incidence of several chronic diseases that result in significant morbidity and mortality in industrialised countries. The available literature, though, makes it difficult to clearly identify SDG health effects because of the wide variability in study methods. However, the current evidence suggests that a dose of at least 500 mg SDG/d for approximately 8 weeks is needed to observe positive effects on cardiovascular risk factors in human patients. Flaxseed and its lignan extracts appear to be safe for most adult populations, though animal studies suggest that pregnant women should limit their exposure. The present review discusses the potential health benefits of SDG in humans, with supporting evidence from animal studies, and offers suggestions for future research.
Asunto(s)
Antioxidantes/uso terapéutico , Butileno Glicoles/uso terapéutico , Lino/química , Glucósidos/uso terapéutico , Lignina/uso terapéutico , Fitoestrógenos/uso terapéutico , Animales , Antioxidantes/metabolismo , Butileno Glicoles/metabolismo , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus/prevención & control , Dieta , Activadores de Enzimas/metabolismo , Activadores de Enzimas/uso terapéutico , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/uso terapéutico , Femenino , Glucósidos/metabolismo , Humanos , Lignina/metabolismo , Neoplasias/prevención & control , Fitoestrógenos/metabolismo , EmbarazoRESUMEN
The objective of the study was to investigate the effect of folate deficiency on formate pharmacokinetics during formate administration in folate-deficient young swine. Methanol is a one of the congeners found in alcoholic beverages. Methanol toxicity is mediated through formic acid and thus plays a significant role in the pathophysiology of alcoholism. Folate is a required cofactor in the metabolism of formate to CO(2) and H(2)O. We investigate the effect of folate deficiency on the pharmacokinetics of formate. Twelve young pigs were pair-matched and randomly placed into 2 groups on acquisition ( approximately 5 weeks). One group was made folate deficient (FFD) by feeding with a folic acid-deficient diet; the other group (FFC) was fed a diet supplemented with folate. Four animals (31-38 kg) from each group were infused (intravenous) with 351 mg/kg of sodium formate. The remaining 2 animals were infused with isotonic sodium chloride solution. Blood samples were collected before and at 10, 20, 30, 45, 60, 90, 120, 180, 240, and 480 minutes post dose and analyzed for formate levels by gas chromatography. Pharmacokinetic parameters were estimated using a noncompartmental approach. Formate (mean +/- SE) accumulation was higher in the FFD group than the FFC group (AUC(0-infinity) of 72.37 +/- 8.29 vs 30.08 +/- 2.58 g min/L, respectively). Elimination was also slower in the FFD group (FFD systemic clearance = 0.12 +/- 0.01 L/min compared with FFC systemic clearance = 0.27 +/- 0.02 L/min). Half-life of elimination was 2.5 times longer in FFD group (113 +/- 1 minute) than in FFC group (45 +/- 6 minutes). Folate deficiency had no influence on the volume of distribution of formate (18.84 +/- 1.05 L in FFD vs 17.21 +/- 1.35 L in FFC). Adequate folate status is important in the elimination of formate. A folate-deficiency state results in a reduction in formate elimination kinetics, which may increase the risk of formate toxicity.