Ginger supplementation does not increase energy expenditure in female adults.

Food components with thermogenic properties are promising antiobesity agents. Ginger (Zingiber officinale Rosc.) bioactive compounds have a capsaicin-like vanillyl portion, which has been attributed to thermogenic effect in previous experimental studies. However, studies conducted in humans have evaluated only the acute thermogenic effect of ginger, and demonstrated contradictory results. We evaluated the effect of long-term consumption of dry ginger extract on the resting energy expenditure (REE) of female adults with high body adiposity. METHODS: This is a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial (NCT02570633). Participants age 18 to 60 y were randomly assigned into two groups: Intervention (600 mg of ginger extract daily) and placebo (cellulose). The intervention lasted 3 mo. Anthropometric measurements, blood pressure, and REE were assessed at each visit. RESULTS: A total of 66 female participants with high body adiposity were included in the analysis (mean age: 29 y [range, 20-55 y]; body mass index: 23.3 ± 2.7), with 30 participants in the ginger group and 36 in the placebo group. There were no significant differences in baseline characteristics between the groups. No differences were observed for group × time interaction on REE. Body composition and blood pressure followed the same pattern (all P > 0.05). CONCLUSIONS: Ginger extract consumption for 3 mo did not change the REE, anthropometric, and clinical data of female adults with excess adiposity.

The link between nutrition and Alzheimer's disease: from prevention to treatment.

Alzheimer's disease (AD) is the most common cause of dementia. To date, there is no effective pharmacological strategy to slow or stop disease progression. In this context, multiple alternative therapeutic strategies have been investigated for AD. This review addresses the potential role of nutrition interventions in AD prevention and treatment. Nutritional strategies for AD have been based on four pillars: maintaining a healthy weight (i.e., prevention and/or treatment of obesity, especially in midlife and prevention of weight loss in the later stages of AD); correction of nutritional deficiencies; adequate consumption of micronutrients (vitamins and minerals), especially those implicated in the pathways of AD pathophysiology; and microbiota modulation.

Acute effects of dry extract of ginger on energy expenditure in eutrophic women: A randomized clinical trial.

BACKGROUND & AIMS: The thermic effect of food (TEF) is one of the components of total energy expenditure (TEE). Some bioactive compounds present in food could be useful to increase TEE. In this context, ginger has been extensively used as a thermogenic food despite no clear effect has been demonstrated yet. Herein, we evaluated the acute thermogenic effect of gingerol, a bioactive compound present in ginger, in healthy women. METHODS: We carried out a randomized double-masked, cross-over and placebo-controlled clinical trial with 20 healthy eutrophic women. Anthropometric, body composition, indirect calorimetry and clinical variables were collected at baseline and throughout the intervention phase. A standardized breakfast was offered together with two dry extract of ginger capsules (5% gingerol) or a placebo (cellulose). Indirect calorimetry, blood pressure, heart rate, axillary temperature and blood collection were assessed at baseline and thereafter, at 30, 60, 120, 180 and 240 min postprandial. The analyses were repeated with a minimum of seven days' washout period. RESULTS: Ginger intake did not increase the TEF of a standardized breakfast compared to the placebo. Oxygen consumption, respiratory quotient, blood pressure, heart rate, axillary temperature and metabolic profile were not different as well. CONCLUSIONS: Our data show that gingerol did not modify the acute TEF in healthy women. More studies in human subjects, using different concentrations of gingerol, administration methods and intervention type (chronic effect) are necessary to clarify the putative thermogenic effect of ginger. Registered at ClinicalTrials.gov (Thermogenic Effect of Ginger - NCT03089593).

Double-blind placebo-controlled randomized clinical trial of ginger (Zingiber officinale Rosc.) in the prophylactic treatment of migraine.

BACKGROUND: Previous studies have shown an analgesic effect of ginger in the acute treatment of migraine, and there is anecdotal evidence of its efficacy in migraine prophylaxis. OBJECTIVE: This study aimed to evaluate the potential of ginger to prevent migraine attacks. METHODS: This double-blind, placebo-controlled randomized clinical trial took place at the Headache Clinic, Universidade Federal de Minas Gerais (Belo Horizonte, Minas Gerais, Brazil), involving 107 patients. Only subjects diagnosed with episodic migraine, aged between 18 and 60 years old, and who were not taking any prophylactic medication, were enrolled in the study. After one month of observation, subjects selected for the study were randomized 1:1 into placebo and treatment groups. Patients received capsules three times per day of 200 mg of dry extract of ginger (5% active ingredient) or placebo (cellulose) for three months. Visits were performed monthly and the patients were asked to fill in a migraine diary. The adherence to treatment was evaluated by counting capsules. RESULTS: The percentage of patients who responded to treatment (i.e. a reduction of 50% in the number of migraine attacks at the end of treatment) did not differ between the groups. There was a decrease in the number of days with severe pain, analgesic use for acute migraine and duration of migraine attacks in both groups, without significant difference between ginger and placebo groups. CONCLUSIONS: Ginger provides no greater benefit in the prophylactic treatment of migraine when compared to placebo. This trial is registered at ClinicalTrials.gov (NCT02570633).

Lamotrigine as a mood stabilizer: insights from the pre-clinical evidence.

INTRODUCTION: Lamotrigine (LTG) is a well-established anticonvulsant that is also approved for the prevention of mood relapses in bipolar disorder. However, the mechanisms underlying LTG mood stabilizing effects remain unclear. Areas covered: Herein, the pre-clinical evidence concerning LTG's' mode of action in depression and mania is reviewed. Bottlenecks and future perspectives for this expanding and promising field are also discussed. Pre-clinical studies have indicated that neurotransmitter systems, especially serotoninergic, noradrenergic and glutamatergic, as well as non-neurotransmitter pathways such as inflammation and oxidative processes might play a role in LTG's antidepressant effects. The mechanisms underlying LTG's anti-manic properties remain to be fully explored, but the available pre-clinical evidence points out to the role of glutamatergic neurotransmission, possibly through AMPA-receptors. Expert opinion: A major limitation of current pre-clinical investigations is that there are no experimental models that recapitulate the complexity of bipolar disorder. Significant methodological differences concerning time and dose of LTG treatment, administration route, animal strains, and behavioral paradigms also hamper the reproducibility of the findings, leading to contradictory conclusions. Moreover, the role of other mechanisms (e.g. inositol phosphate and GSK3ß pathways) implicated in the mode of action of different mood-stabilizers must also be consolidated with LTG.

Double-blind placebo-controlled randomized clinical trial of ginger ( Zingiber officinale Rosc.) addition in migraine acute treatment.

BACKGROUND: Previous studies have demonstrated the analgesic effects of ginger in different conditions, but evidence about its efficacy in migraine treatment is scarce. OBJECTIVE: This study aimed to evaluate the potential of ginger to improve acute migraine as an add-on strategy to standard treatment. METHODS: A double-blind placebo-controlled randomized clinical trial in the emergency room of a general hospital was conducted. Patients who sought medical care at the time of migraine attack were enrolled in this study. Only adults with episodic migraine (one to six migraine attacks per month) with or without aura were included. Sixty participants were randomized into two groups in which they received 400 mg of ginger extract (5% active ingredient) or placebo (cellulose), in addition to an intravenous drug (100 mg of ketoprofen) to treat the migraine attack. Patients filled a headache diary before, 0.5 h, 1 h, 1.5 h and 2 h after the medication. Pain severity, functional status, migraine symptoms and treatment satisfaction were also recorded. RESULTS: Patients treated with ginger showed significantly better clinical response after 1 h ( p = 0.04), 1.5 h ( p = 0.01) and 2 h ( p = 0.04). Furthermore, ginger treatment promoted reduction in pain and improvement on functional status at all times assessed. CONCLUSIONS: The addition of ginger to non-steroidal anti-inflammatory drugs may contribute to the treatment of migraine attack. This trial is registered at ClinicalTrials.gov (NCT02568644).

Effects of the inspiratory muscle training and aerobic training on respiratory and functional parameters, inflammatory biomarkers, redox status and quality of life in hemodialysis patients: A randomized clinical trial.

OBJECTIVE: Evaluate and compare the isolated and combined effects of Inspiratory Muscle Training (IMT) and Aerobic Training (AT) on respiratory and functional parameters, inflamatory biomarkers, redox status and health-related quality of life (HRQoL) in hemodialysis patients. METHODS: A randomised controlled trial with factorial allocation and intention-to-treat analysis was performed in hemodialysis patients. Volunteers were randomly assigned to performe 8-weeks of IMT at 50% of maximal inspiratory pressure (MIP), low intensity AT or combined training (CT). Before the interventions, all the volunteers went 8-weeks through a control period (without training). Measures are taken at baseline, 8-week (after control period) and 16-week (after the interventions). Primary outcomes were functional capacity (incremental shuttle walk test), MIP and lower limbs strength (Sit-to-Stand test of 30 seconds). Plasma levels of interleukin-6 (IL-6), soluble tumor necrosis factor receptor 1 (sTNFR1) and 2 (sTNFR2), adiponectin, resistin and leptin, redox status parameters and HRQoL (KDQOL-SF questionnaire) were the scondary outcomes. Data analyses were performed by two-way repeated measurements ANOVA. RESULTS: 37 hemodialysis patients aged 48.2 years old (IC95% 43.2-54.7) were randomized. Increase of MIP, functional capacity, lower limbs strength and resistin levels, and reduction of sTNFR2 levels in 16-week, compared to baseline and 8-week, were observed in all the groups (p<0.001). IMT improved functional capacity, MIP and lower limbs strength in 96.7m (IC95% 5.6-189.9), 34.5cmH2O (IC95% 22.4-46.7) and 2.2repetitions (IC95% 1.1-3.2) respectively. Increase in resistin leves and reduction in sTNFR2 leves after IMT was 0.8ng/dL (IC95% 0.5-1.1) and 0.8ng/dL (IC95% 0.3-1.3), respectively, without between-group differences. Compared to baseline and 8-week, adiponectin levels (p<0.001) and fatigue domain of the HRQoL (p<0.05) increased in 16-week only in CT. CONCLUSION: IMT, AT and CT improved functional parameters and modulated inflammatory biomarkers, in addition, IMT provoked a similar response to low intensity AT in hemodialysis patients. TRIAL REGISTRATION: Registro Brasileiro de Ensaios clínicos RBR-4hv9rs.

The preclinical discovery and development of quetiapine for the treatment of mania and depression.

INTRODUCTION: Bipolar disorder is a chronic disabling condition characterized by alternating manic and depressive episodes. Bipolar disorder has been associated with functional impairment, poor quality of life, morbidity and mortality. Despite its significant clinical, social and economic burden, treatment options for bipolar disorder are still limited. Several clinical trials have shown efficacy of the atypical antipsychotic quetiapine (QTP) in the treatment of this condition. However, the mechanisms underlying the antidepressant and anti-manic effects of QTP remain poorly understood. Areas covered: The article provides the emerging evidence from pre-clinical studies regarding the antidepressant and anti-manic mechanisms of action of QTP. In combination with its primary active metabolite norquetiapine, QTP modulates several neurotransmitter systems, including serotonin, dopamine, noradrenaline and histamine. QTP also seems to influence mediators of the immune system. Expert opinion: Pre-clinical studies have provided valuable information on the potential antidepressant mechanisms of action of QTP, but pre-clinical studies on QTP's anti-manic effects are still scarce. A major problem refers to the lack of valid experimental models for bipolar disorder. Additionally, immune and genetic based studies are largely descriptive. The role of the QTP metabolite norquetiapine in modulating non-neurotransmitter systems also needs to be further addressed.

A Neuroprotective Effect of the Glutamate Receptor Antagonist MK801 on Long-Term Cognitive and Behavioral Outcomes Secondary to Experimental Cerebral Malaria.

Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection, which can result in long-term cognitive and behavioral deficits despite successful anti-malarial therapy. Due to the substantial social and economic burden of CM, the development of adjuvant therapies is a scientific goal of highest priority. Apart from vascular and immune responses, changes in glutamate system have been reported in CM pathogenesis suggesting a potential therapeutic target. Based on that, we hypothesized that interventions in the glutamatergic system induced by blockage of N-methyl-D-aspartate (NMDA) receptors could attenuate experimental CM long-term cognitive and behavioral outcomes. Before the development of evident CM signs, susceptible mice infected with Plasmodium berghei ANKA (PbA) strain were initiated on treatment with dizocilpine maleate (MK801, 0.5 mg/kg), a noncompetitive NMDA receptor antagonist. On day 5 post-infection, mice were treated orally with a 10-day course chloroquine (CQ, 30 mg/kg). Control mice also received saline, CQ or MK801 + CQ therapy. After 10 days of cessation of CQ treatment, magnetic resonance images (MRI), behavioral and immunological assays were performed. Indeed, MK801 combined with CQ prevented long-term memory impairment and depressive-like behavior following successful PbA infection resolution. In addition, MK801 also modulated the immune system by promoting a balance of TH1/TH2 response and upregulating neurotrophic factors levels in the frontal cortex and hippocampus. Moreover, hippocampus abnormalities observed by MRI were partially prevented by MK801 treatment. Our results indicate that NMDA receptor antagonists can be neuroprotective in CM and could be a valuable adjuvant strategy for the management of the long-term impairment observed in CM.

Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial.

INTRODUCTION: Parkinson's disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target. METHODS: From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H(1)-MRS). RESULTS: We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H(1)-MRS measures. However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05). CONCLUSIONS: Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.

Effect of salivary stimulation therapies on salivary flow and chemotherapy-induced mucositis: a preliminary study.

OBJECTIVE: The objective of this study was to evaluate the effect of salivary stimulation therapies on the salivary flow, oral mucositis, and salivary cytokine levels in patients receiving allogeneic hematopoietic stem cell transplantation. STUDY DESIGN: Thirty-five eligible patients were randomized into 4 groups: control, mechanical sialogogue, transcutaneous electrical nerve stimulation (TENS) sialogogue, and combined mechanical/electrical sialogogue. Saliva was collected from patients before transplantation and at days 3, 7, and 14 after transplantation. The volume was measured and salivary cytokines were assessed using enzyme-linked immunosorbent assay. RESULTS: By day 14, resting and stimulated salivary flow levels were diminished. Resting salivary flow rates decreased the most in the control and mechanical groups. In contrast, TENS alone or in combination with mechanical stimulatory therapy benefited the patients. TENS-treated patients showed increase in resting salivary flow. Also, the groups treated with TENS had fewer patients affected by grades 3 and 4 mucositis, and less mucositis was associated with better patient survival (P = .027). CONCLUSIONS: TENS-associated salivary stimulation therapies minimized the reduction of salivary flow and prevented severe chemotherapy-induced oral mucositis.

Diagnosis of Alzheimers disease in Brazil: supplementary exams / Diagnóstico de doença de Alzheimer no Brasil: exames complementares

This article presents a review of the recommendations on supplementary exams employed for the clinical diagnosis of Alzheimers disease (AD) in Brazil published in 2005. A systematic assessment of the consensus reached in other countries, and of articles on AD diagnosis in Brazil available on the PUBMED and LILACS medical databases, was carried out. Recommended laboratory exams included complete blood count, serum creatinine, thyroid stimulating hormone (TSH), albumin, hepatic enzymes, Vitamin B12, folic acid, calcium, serological reactions for syphilis and serology for HIV in patients aged younger than 60 years with atypical clinical signs or suggestive symptoms. Structural neuroimaging, computed tomography or preferably magnetic resonance exams, are indicated for diagnostic investigation of dementia syndrome to rule out secondary etiologies. Functional neuroimaging exams (SPECT and PET), when available, increase diagnostic reliability and assist in the differential diagnosis of other types of dementia. The cerebrospinal fluid exam is indicated in cases of pre-senile onset dementia with atypical clinical presentation or course, for communicant hydrocephaly, and suspected inflammatory, infectious or prion disease of the central nervous system. Routine electroencephalograms aid the differential diagnosis of dementia syndrome with other conditions which impair cognitive functioning. Genotyping of apolipoprotein E or other susceptibility polymorphisms is not recommended for diagnostic purposes or for assessing the risk of developing the disease. Biomarkers related to the molecular alterations in AD are largely limited to use exclusively in research protocols, but when available can contribute to improving the accuracy of diagnosis of the disease.

Este artigo apresenta revisão das recomendações sobre os exames complementares empregados para o diagnóstico clínico de doença de Alzheimer (DA) no Brasil, publicadas em 2005. Foram avaliados de modo sistemático consensos elaborados em outros países e artigos sobre o diagnóstico de DA no Brasil disponíveis no PUBMED ou LILACS. Os exames laboratoriais recomendados são hemograma completo, creatinina sérica, hormônio tíreo-estimulante, albumina, enzimas hepáticas, vitamina B12, ácido fólico, cálcio, reações sorológicas para sífilis e, em pacientes com idade inferior a 60 anos, com apresentações clínicas atípicas ou com sintomas sugestivos, sorologia para HIV. Exame de neuroimagem estrutural, tomografia computadorizada ou ? preferencialmente ? ressonância magnética, é indicado na investigação diagnóstica de síndrome demencial, para exclusão de causas secundárias. Exames de neuroimagem funcional (SPECT e PET), quando disponíveis, aumentam a confiabilidade diagnóstica e auxiliam no diagnóstico diferencial de outras formas de demência. O exame do líquido cefalorraquidiano é preconizado em casos de demência de início pré-senil, com apresentação ou curso clínico atípicos, hidrocefalia comunicante e quando há suspeita de doença inflamatória, infecciosa ou priônica do sistema nervoso central. O eletroencefalograma de rotina auxilia no diagnóstico diferencial de síndrome demencial com outras condições que interferem no funcionamento cognitivo. A genotipagem da apolipoproteína E ou de outros polimorfismos de susceptibilidade não é recomendada com finalidade diagnóstica ou para avaliação de risco de desenvolvimento da doença. Os biomarcadores relacionados às alterações moleculares da DA ainda são de uso quase exclusivo em protocolos de pesquisa, mas quando disponíveis podem contribuir para maior precisão diagnóstica da doença.

Diagnosis of Alzheimer's disease in Brazil: Supplementary exams.

This article presents a review of the recommendations on supplementary exams employed for the clinical diagnosis of Alzheimer's disease (AD) in Brazil published in 2005. A systematic assessment of the consensus reached in other countries, and of articles on AD diagnosis in Brazil available on the PUBMED and LILACS medical databases, was carried out. Recommended laboratory exams included complete blood count, serum creatinine, thyroid stimulating hormone (TSH), albumin, hepatic enzymes, Vitamin B12, folic acid, calcium, serological reactions for syphilis and serology for HIV in patients aged younger than 60 years with atypical clinical signs or suggestive symptoms. Structural neuroimaging, computed tomography or - preferably - magnetic resonance exams, are indicated for diagnostic investigation of dementia syndrome to rule out secondary etiologies. Functional neuroimaging exams (SPECT and PET), when available, increase diagnostic reliability and assist in the differential diagnosis of other types of dementia. The cerebrospinal fluid exam is indicated in cases of pre-senile onset dementia with atypical clinical presentation or course, for communicant hydrocephaly, and suspected inflammatory, infectious or prion disease of the central nervous system. Routine electroencephalograms aid the differential diagnosis of dementia syndrome with other conditions which impair cognitive functioning. Genotyping of apolipoprotein E or other susceptibility polymorphisms is not recommended for diagnostic purposes or for assessing the risk of developing the disease. Biomarkers related to the molecular alterations in AD are largely limited to use exclusively in research protocols, but when available can contribute to improving the accuracy of diagnosis of the disease.

Este artigo apresenta revisão das recomendações sobre os exames complementares empregados para o diagnóstico clínico de doença de Alzheimer (DA) no Brasil, publicadas em 2005. Foram avaliados de modo sistemático consensos elaborados em outros países e artigos sobre o diagnóstico de DA no Brasil disponíveis no PUBMED ou LILACS. Os exames laboratoriais recomendados são hemograma completo, creatinina sérica, hormônio tíreo-estimulante, albumina, enzimas hepáticas, vitamina B12, ácido fólico, cálcio, reações sorológicas para sífilis e, em pacientes com idade inferior a 60 anos, com apresentações clínicas atípicas ou com sintomas sugestivos, sorologia para HIV. Exame de neuroimagem estrutural, tomografia computadorizada ou ­ preferencialmente ­ ressonância magnética, é indicado na investigação diagnóstica de síndrome demencial, para exclusão de causas secundárias. Exames de neuroimagem funcional (SPECT e PET), quando disponíveis, aumentam a confiabilidade diagnóstica e auxiliam no diagnóstico diferencial de outras formas de demência. O exame do líquido cefalorraquidiano é preconizado em casos de demência de início pré-senil, com apresentação ou curso clínico atípicos, hidrocefalia comunicante e quando há suspeita de doença inflamatória, infecciosa ou priônica do sistema nervoso central. O eletroencefalograma de rotina auxilia no diagnóstico diferencial de síndrome demencial com outras condições que interferem no funcionamento cognitivo. A genotipagem da apolipoproteína E ou de outros polimorfismos de susceptibilidade não é recomendada com finalidade diagnóstica ou para avaliação de risco de desenvolvimento da doença. Os biomarcadores relacionados às alterações moleculares da DA ainda são de uso quase exclusivo em protocolos de pesquisa, mas quando disponíveis podem contribuir para maior precisão diagnóstica da doença.