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1.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33947005

RESUMO

Beneficial metabolic effects of inorganic nitrate (NO3-) and nitrite (NO2-) in type 2 diabetes mellitus (T2DM) have been documented in animal experiments; however, this is not the case for humans. Although it has remained an open question, the redox environment affecting the conversion of NO3- to NO2- and then to NO is suggested as a potential reason for this lost-in-translation. Ascorbic acid (AA) has a critical role in the gastric conversion of NO2- to NO following ingestion of NO3-. In contrast to AA-synthesizing species like rats, the lack of ability to synthesize AA and a lower AA body pool and plasma concentrations may partly explain why humans with T2DM do not benefit from NO3-/NO2- supplementation. Rats also have higher AA concentrations in their stomach tissue and gastric juice that can significantly potentiate gastric NO2--to-NO conversion. Here, we hypothesized that the lack of beneficial metabolic effects of inorganic NO3- in patients with T2DM may be at least in part attributed to species differences in AA metabolism and also abnormal metabolism of AA in patients with T2DM. If this hypothesis is proved to be correct, then patients with T2DM may need supplementation of AA to attain the beneficial metabolic effects of inorganic NO3- therapy.


Assuntos
Ácido Ascórbico/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Nitratos/farmacocinética , Oxirredutases do Álcool/deficiência , Animais , Arginina/metabolismo , Ácido Ascórbico/metabolismo , Ácido Ascórbico/farmacologia , Deficiência de Ácido Ascórbico/complicações , Deficiência de Ácido Ascórbico/tratamento farmacológico , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/complicações , Dieta , Suco Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Glucose/metabolismo , Cobaias , Homeostase , Humanos , Insulina/metabolismo , Camundongos , Modelos Animais , Nitratos/administração & dosagem , Nitratos/metabolismo , Nitratos/uso terapêutico , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Nitritos/metabolismo , Nitritos/farmacocinética , Necessidades Nutricionais , Oxirredução , Ratos , Especificidade da Espécie
2.
Clin Nutr ESPEN ; 43: 39-48, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34024545

RESUMO

BACKGROUND: The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population. METHODS: Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity. RESULTS: The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of COVID-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population. CONCLUSION: There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with a combination of moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups.


Assuntos
COVID-19/tratamento farmacológico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Fatores Imunológicos/uso terapêutico , Oligoelementos/uso terapêutico , Vitaminas/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , COVID-19/imunologia , Comorbidade , Ácidos Graxos Ômega-3/farmacologia , Feminino , Humanos , Fatores Imunológicos/farmacologia , Masculino , Micronutrientes/farmacologia , Micronutrientes/uso terapêutico , Estado Nutricional , Pandemias , Gravidez , SARS-CoV-2 , Selênio/farmacologia , Selênio/uso terapêutico , Suíça , Oligoelementos/farmacologia , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Vitaminas/farmacologia , Zinco/farmacologia , Zinco/uso terapêutico
3.
Artigo em Alemão | MEDLINE | ID: mdl-34038976

RESUMO

Vitamin C deficiency often occurs in critical illness and especially in patients with sepsis. Low plasma levels correlate with organ dysfunction and outcome parameters. Vitamin C offers pleiotropic effects possibly attenuating pathophysiology in sepsis. This includes antioxidative effects like scavenging reactive oxygen species or restoring other antioxidants. Vitamin C is a cofactor for norepinephrine biosynthesis and it protects endothelial function. In addition, it modulates immune response. A combined therapy with vitamin C, hydrocortisone and thiamine could be beneficial because of synergistic effects. Some clinical studies have shown reduced mortality due to vitamin C alone or in combination with hydrocortisone and thiamine, others do not. Adverse events are rare. So data supporting a therapy with vitamin C is still unclear. Further randomised controlled trials are necessary.


Assuntos
Ácido Ascórbico , Sepse , Ácido Ascórbico/uso terapêutico , Humanos , Hidrocortisona , Sepse/tratamento farmacológico , Tiamina , Vitaminas
5.
Food Funct ; 12(9): 3787-3798, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33977997

RESUMO

Liver ischemia-reperfusion injury (IRI) is a phenomenon inherent to hepatic surgery that severely compromises the organ functionality, whose underlying mechanisms involve cellular and molecular interrelated processes leading to the development of an excessive inflammatory response. Liver resident cells and those recruited in response to injury generate pro-inflammatory signals such as reactive oxygen species, cytokines, chemokines, proteases and lipid mediators that contribute to hepatocellular necrosis and apoptosis. Besides, dying hepatocytes release damage-associated molecular patterns that actívate inflammasomes to further stimulate inflammatory responses leading to massive cell death. Since liver IRI is a complication of hepatic surgery in man, extensive preclinical studies have assessed potential protective strategies, including the supplementation with natural compounds, with the objective to downregulate nuclear factor-κB functioning, the main effector of inflammatory responses. This can be accomplished by either the activation of peroxisome proliferator-activated receptor-α, G protein-coupled receptor 120 or antioxidant signaling pathways, the synthesis of specific pro-resolving mediators, downregulation of Toll-like receptor 4 activity or additional contributory mechanisms that are beginning to be understood. The latter aspect is a crucial issue to be accomplished in preclinical studies, in order to establish adequate conditions for the supplementation with natural products before major liver surgeries in man involving warm IR, such as hepatic trauma or resection of large intrahepatic tumors.


Assuntos
Produtos Biológicos/uso terapêutico , Ácidos Graxos Insaturados/uso terapêutico , Fígado/irrigação sanguínea , Álcool Feniletílico/análogos & derivados , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/terapia , Vitaminas/uso terapêutico , Animais , Ácido Ascórbico/uso terapêutico , Humanos , Fígado/fisiopatologia , Álcool Feniletílico/uso terapêutico , Traumatismo por Reperfusão/fisiopatologia , Vitamina E/uso terapêutico
6.
Nutrients ; 13(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916257

RESUMO

Vitamin C is an essential nutrient that serves as antioxidant and plays a major role as co-factor and modulator of various pathways of the immune system. Its therapeutic effect during infections has been a matter of debate, with conflicting results in studies of respiratory infections and in critically ill patients. This comprehensive review aimed to summarize the current evidence regarding the use of vitamin C in the prevention or treatment of patients with SARS-CoV2 infection, based on available publications between January 2020 and February 2021. Overall, 21 publications were included in this review, consisting of case-reports and case-series, observational studies, and some clinical trials. In many of the publications, data were incomplete, and in most clinical trials the results are still pending. No studies regarding prevention of COVID-19 with vitamin C supplementation were found. Although some clinical observations reported improved medical condition of patients with COVID-19 treated with vitamin C, available data from controlled studies are scarce and inconclusive. Based on the theoretical background presented in this article, and some preliminary encouraging studies, the role of vitamin C in the treatment of patients with SARS-CoV-2 infection should be further investigated.


Assuntos
Ácido Ascórbico/uso terapêutico , COVID-19/tratamento farmacológico , Vitaminas/uso terapêutico , Adulto , Idoso , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Ácido Ascórbico/administração & dosagem , Criança , Ensaios Clínicos como Assunto , Suplementos Nutricionais , Vias de Administração de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Índice de Gravidade de Doença , Resultado do Tratamento , Vitaminas/administração & dosagem
7.
Nutrients ; 13(4)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807280

RESUMO

Fatigue is common not only in cancer patients but also after viral and other infections. Effective treatment options are still very rare. Therefore, the present knowledge on the pathophysiology of fatigue and the potential positive impact of treatment with vitamin C is illustrated. Additionally, the effectiveness of high-dose IV vitamin C in fatigue resulting from various diseases was assessed by a systematic literature review in order to assess the feasibility of vitamin C in post-viral, especially in long COVID, fatigue. Nine clinical studies with 720 participants were identified. Three of the four controlled trials observed a significant decrease in fatigue scores in the vitamin C group compared to the control group. Four of the five observational or before-and-after studies observed a significant reduction in pre-post levels of fatigue. Attendant symptoms of fatigue such as sleep disturbances, lack of concentration, depression, and pain were also frequently alleviated. Oxidative stress, inflammation, and circulatory disorders, which are important contributors to fatigue, are also discussed in long COVID fatigue. Thus, the antioxidant, anti-inflammatory, endothelial-restoring, and immunomodulatory effects of high-dose IV vitamin C might be a suitable treatment option.


Assuntos
Ácido Ascórbico/uso terapêutico , COVID-19/complicações , Fadiga/tratamento farmacológico , Fadiga/etiologia , SARS-CoV-2 , Ácido Ascórbico/administração & dosagem , COVID-19/patologia , Estudos de Viabilidade , Humanos , Injeções Intravenosas
8.
Chem Biol Interact ; 342: 109476, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33872575

RESUMO

Ketamine is the prototype for glutamate-based fast-acting antidepressants. The establishment of ketamine-like drugs is still a challenge and ascorbic acid has emerged as a candidate. This study investigated the ascorbic acid's ability to induce a fast antidepressant-like response and to improve hippocampal synaptic markers in mice subjected to chronic corticosterone (CORT) administration. CORT was administered for 21 days, followed by a single administration of ascorbic acid (1 mg ∕Kg, p.o.), ketamine (1 mg ∕Kg, i.p.) or fluoxetine (10 mg ∕Kg, p.o.) in mice. Depressive-like behavior, hippocampal synaptic proteins immunocontent, dendrite spines density in the dentate gyrus (DG) were analyzed 24 h following treatments. The administration of ascorbic acid or ketamine, but not fluoxetine, counteracted CORT-induced depressive-like behavior in the tail suspension test (TST). CORT administration reduced PSD-95, GluA1, and synapsin (synaptic markers) immunocontent, and these alterations were reversed by ascorbic acid or ketamine, but only ketamine reversed the CORT-induced reduction on GluA1 immunocontent. In the ventral and dorsal DG, CORT decreased filopodia-, thin- and stubby-shaped spines, while ascorbic acid and ketamine abolished this alteration only in filopodia spines. Ascorbic acid and ketamine increased mushroom-shaped spines density in ventral and dorsal DG. Therefore, the results show that a single administration of ascorbic acid, in a way similar to ketamine, rapidly elicits an antidepressant-like response and reverses hippocampal synaptic deficits caused by CORT, an effect associated with increased levels of synaptic proteins and dendritic remodeling.


Assuntos
Antidepressivos/uso terapêutico , Ácido Ascórbico/uso terapêutico , Depressão/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Animais , Corticosterona , Espinhas Dendríticas/efeitos dos fármacos , Depressão/induzido quimicamente , Feminino , Elevação dos Membros Posteriores , Ketamina/uso terapêutico , Camundongos , Fármacos Neuroprotetores/uso terapêutico
9.
Biomed Res Int ; 2021: 6638858, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33681359

RESUMO

The effectiveness of additional usage of adjuvants for bowel preparation is still unclear. This study compared 1L polyethylene glycol plus ascorbic acid with adjuvant drug regimens (1L PEG-AA, lower volume) with 2L polyethylene glycol plus ascorbic acid (2L PEG-A, low volume) to evaluate whether the adjuvants can be used to reduce the standard dosage of purgative further. The PubMed/MEDLINE, EMBASE, Cochrane Library, and Web of Science database were searched for randomized controlled trials (RCTs). The primary outcome was the efficacy of bowel preparation, and the secondary outcomes were patients' tolerability and complication rate. The overall quality of evidence was assessed using the GRADEpro guideline development tool. Five RCTs with a total of 1013 patients from Korea were included. The majority of patients were outpatients from different hospitals. The pooled data showed no significant difference in the adequate bowel preparation rate (89.3% versus 89.4%, RR 1, 95% CI 0.95-1.05, I 2 = 47%) as well as in the complication rate (RR for nausea 1.22, 95% CI 0.89-1.65, I 2 = 49%; RR for bloating 0.96, 95% CI 0.73-1.28, I 2 = 0%; RR for vomiting 0.69, 95% CI 0.32-1.50, I 2 = 33%; RR for abdominal pain 1.01, 95% CI 0.61-1.69, I 2 = 0%). But a significantly higher willingness rate was observed in the lower volume (85.1% versus 67.9%, RR 1.25, 95% CI 1.14-1.38, I 2 = 46%). The quality of primary outcome evidence was moderate. The findings of this meta-analysis revealed that 1L PEG-AA may be a viable alternative to 2L PEG-A, with comparable effectiveness, better patient preference, and no statistically significant adverse event occurrence.


Assuntos
Ácido Ascórbico , Catárticos , Polietilenoglicóis , Ácido Ascórbico/efeitos adversos , Ácido Ascórbico/uso terapêutico , Catárticos/efeitos adversos , Catárticos/uso terapêutico , Humanos , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Nutrients ; 13(2)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671646

RESUMO

Gout, known as "the disease of the kings", is the most frequent type of arthritis. It results from sustained hyperuricemia that leads to monosodium urate crystal deposition in joint structures and soft tissue. Environmental factors such as diet affect the incidence of gout; there is a known relationship between the occurrence of an acute attack of gout and the consumption of alcohol and meat; and a low purine diet is a widely recognized nonpharmacological method of supplementing the treatment and preventing recurrence of arthritis. This review aims to summarize the current knowledge about the role of vitamin C in prevention and treatment of gout. A PubMed/Medline database search on the role of vitamin C in purine metabolism was done. Reports from in vitro and animal studies seem to be promising and to allow explanation of the physiological relationship between vitamin C and uric acid. Most epidemiological studies indicate a significant correlation between high vitamin C intake and lower serum uric acid levels. Despite promising observations, there are few observational and interventional studies, and their results do not clearly define the benefits of a high daily intake of vitamin C in preventing the development and recurrence of gout.


Assuntos
Ácido Ascórbico/uso terapêutico , Gota/tratamento farmacológico , Dieta , Gota/patologia , Humanos , Hiperuricemia/prevenção & controle
12.
Biochem Biophys Res Commun ; 551: 46-53, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33714759

RESUMO

Anaplastic thyroid cancer (ATC) is a rare but highly lethal disease. So far, there is no available established treatment which can prolong its survival. In this regard, effective therapies are urgently needed. Vitamin C widely serves as an anti-cancer agent. However, the potential effects of vitamin C against thyroid tumorigenesis remained unclear. The present study demonstrated that vitamin C could significantly inhibit ATC cells growth through ferroptosis activation, evidenced by the GPX4 inactivation, ROS accumulation and iron-dependent lipid peroxidation. Our results demonstrated that vitamin C treatment induced ferritinophagy and subsequent degradation of ferritin, leading to the release of free iron. Excessive iron further triggered ROS generation via Fenton reaction. The positive feedback mediated by ROS and iron sustained lipid peroxidation and further resulted in ferroptosis of ATC cells. The better understanding of the anti-cancer mechanisms of vitamin C provides a potential strategy for ATC therapy.


Assuntos
Ácido Ascórbico/farmacologia , Autofagia/efeitos dos fármacos , Ferritinas/metabolismo , Ferroptose/efeitos dos fármacos , Carcinoma Anaplásico da Tireoide/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ácido Ascórbico/uso terapêutico , Carcinogênese/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos , Estresse Oxidativo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/metabolismo
13.
Int J Mol Sci ; 22(4)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669456

RESUMO

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19), is a worldwide pandemic, as declared by the World Health Organization (WHO). It is a respiratory virus that infects people of all ages. Although it may present with mild to no symptoms in most patients, those who are older, immunocompromised, or with multiple comorbidities may present with severe and life-threatening infections. Throughout history, nutraceuticals, such as a variety of phytochemicals from medicinal plants and dietary supplements, have been used as adjunct therapies for many disease conditions, including viral infections. Appropriate use of these adjunct therapies with antiviral proprieties may be beneficial in the treatment and/or prophylaxis of COVID-19. In this review, we provide a comprehensive summary of nutraceuticals, such as vitamins C, D, E, zinc, melatonin, and other phytochemicals and function foods. These nutraceuticals may have potential therapeutic efficacies in fighting the threat of the SARS-CoV-2/COVID-19 pandemic.


Assuntos
COVID-19/tratamento farmacológico , Suplementos Nutricionais , Melatonina/uso terapêutico , Vitaminas/uso terapêutico , Zinco/uso terapêutico , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Suplementos Nutricionais/análise , Alimento Funcional/análise , Humanos , Melatonina/farmacologia , SARS-CoV-2/efeitos dos fármacos , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Vitaminas/farmacologia , Zinco/farmacologia
14.
Cancer Sci ; 112(5): 1975-1986, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33606344

RESUMO

Tissue factor (TF), the trigger protein of the extrinsic blood coagulation cascade, is abundantly expressed in various cancers including gastric cancer. Anti-TF monoclonal antibodies (mAbs) capable of targeting cancers have been successfully applied to armed antibodies such as antibody-drug conjugates (ADCs) and molecular imaging probes. We prepared an anti-TF mAb, clone 1084, labeled with astatine-211 (211 At), as a promising alpha emitter for cancer treatment. Alpha particles are characterized by high linear energy transfer and a range of 50-100 µm in tissue. Therefore, selective and efficient tumor accumulation of alpha emitters results in potent antitumor activities against cancer cells with minor effects on normal cells adjacent to the tumor. Although the 211 At-conjugated clone 1084 (211 At-anti-TF mAb) was disrupted by an 211 At-induced radiochemical reaction, we demonstrated that astatinated anti-TF mAbs eluted in 0.6% or 1.2% sodium ascorbate (SA) solution were protected from antibody denaturation, which contributed to the maintenance of cellular binding activities and cytocidal effects of this immunoconjugate. Although body weight loss was observed in mice administered a 1.2% SA solution, the loss was transient and the radioprotectant seemed to be tolerable in vivo. In a high TF-expressing gastric cancer xenograft model, 211 At-anti-TF mAb in 1.2% SA exerted a significantly greater antitumor effect than nonprotected 211 At-anti-TF mAb. Moreover, the antitumor activities of the protected immunoconjugate in gastric cancer xenograft models were dependent on the level of TF in cancer cells. These findings suggest the clinical availability of the radioprotectant and applicability of clone 1084 to 211 At-radioimmunotherapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Ácido Ascórbico/uso terapêutico , Astato/uso terapêutico , Imunoconjugados/uso terapêutico , Radioimunoterapia/métodos , Neoplasias Gástricas/terapia , Tromboplastina/imunologia , Animais , Anticorpos Monoclonais Humanizados/farmacocinética , Astato/farmacocinética , Coagulação Sanguínea/fisiologia , Peso Corporal , Linhagem Celular Tumoral , Feminino , Xenoenxertos , Humanos , Imunoconjugados/química , Imunoconjugados/farmacocinética , Transferência Linear de Energia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Desnaturação Proteica , Protetores contra Radiação/uso terapêutico , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Tromboplastina/metabolismo
16.
Eur J Med Res ; 26(1): 20, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33573699

RESUMO

BACKGROUND: Vitamin C is an essential water-soluble nutrient that functions as a key antioxidant and has been proven to be effective for boosting immunity. In this study, we aimed to assess the efficacy of adding high-dose intravenous vitamin C (HDIVC) to the regimens for patients with severe COVID-19 disease. METHODS: An open-label, randomized, and controlled trial was conducted on patients with severe COVID-19 infection. The case and control treatment groups each consisted of 30 patients. The control group received lopinavir/ritonavir and hydroxychloroquine and the case group received HDIVC (6 g daily) added to the same regimen. RESULTS: There were no statistically significant differences between two groups with respect to age and gender, laboratory results, and underlying diseases. The mean body temperature was significantly lower in the case group on the 3rd day of hospitalization (p = 0.001). Peripheral capillary oxygen saturations (SpO2) measured at the 3rd day of hospitalization was also higher in the case group receiving HDIVC (p = 0.014). The median length of hospitalization in the case group was significantly longer than the control group (8.5 days vs. 6.5 days) (p = 0.028). There was no significant difference in SpO2 levels at discharge time, the length of intensive care unit (ICU) stay, and mortality between the two groups. CONCLUSIONS: We did not find significantly better outcomes in the group who were treated with HDIVC in addition to the main treatment regimen at discharge. Trial registration irct.ir (IRCT20200411047025N1), April 14, 2020.


Assuntos
Antivirais/uso terapêutico , Ácido Ascórbico/administração & dosagem , COVID-19/tratamento farmacológico , Antivirais/administração & dosagem , Ácido Ascórbico/uso terapêutico , Temperatura Corporal , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Unidades de Terapia Intensiva , Tempo de Internação , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/virologia , Ritonavir/uso terapêutico , Resultado do Tratamento
17.
JAMA Netw Open ; 4(2): e210369, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33576820

RESUMO

Importance: There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression. Objective: To examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection. Design, Setting, and Participants: This multicenter, single health system randomized clinical factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and Florida. The trial was conducted from April 27, 2020, to October 14, 2020. Intervention: Patients were randomized in a 1:1:1:1 allocation ratio to receive either 10 days of zinc gluconate (50 mg), ascorbic acid (8000 mg), both agents, or standard of care. Outcomes: The primary end point was the number of days required to reach a 50% reduction in symptoms, including severity of fever, cough, shortness of breath, and fatigue (rated on a 4-point scale for each symptom). Secondary end points included days required to reach a total symptom severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed medications, and adverse effects of the study supplements. Results: A total of 214 patients were randomized, with a mean (SD) age of 45.2 (14.6) years and 132 (61.7%) women. The study was stopped for a low conditional power for benefit with no significant difference among the 4 groups for the primary end point. Patients who received usual care without supplementation achieved a 50% reduction in symptoms at a mean (SD) of 6.7 (4.4) days compared with 5.5 (3.7) days for the ascorbic acid group, 5.9 (4.9) days for the zinc gluconate group, and 5.5 (3.4) days for the group receiving both (overall P = .45). There was no significant difference in secondary outcomes among the treatment groups. Conclusions and Relevance: In this randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements did not significantly decrease the duration of symptoms compared with standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT04342728.


Assuntos
Ácido Ascórbico/uso terapêutico , COVID-19/tratamento farmacológico , Suplementos Nutricionais , Zinco/uso terapêutico , Adulto , Assistência Ambulatorial , Antioxidantes/uso terapêutico , COVID-19/complicações , Tosse/tratamento farmacológico , Tosse/etiologia , Dispneia/tratamento farmacológico , Dispneia/etiologia , Fadiga/tratamento farmacológico , Fadiga/etiologia , Feminino , Febre/tratamento farmacológico , Febre/etiologia , Gluconatos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Índice de Gravidade de Doença , Padrão de Cuidado , Oligoelementos/uso terapêutico , Resultado do Tratamento
18.
Aging (Albany NY) ; 13(5): 7020-7034, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33638944

RESUMO

BACKGROUND: The inflammatory reaction is the main cause of acute respiratory distress syndrome and multiple organ failure in patients with Coronavirus disease 2019, especially those with severe and critical illness. Several studies suggested that high-dose vitamin C reduced inflammatory reaction associated with sepsis and acute respiratory distress syndrome. This study aimed to determine the efficacy and safety of high-dose vitamin C in Coronavirus disease 2019. METHODS: We included 76 patients with Coronavirus disease 2019, classified into the high-dose vitamin C group (loading dose of 6g intravenous infusion per 12 hr on the first day, and 6g once for the following 4 days, n=46) and the standard therapy group (standard therapy alone, n=30). RESULTS: The risk of 28-day mortality was reduced for the high-dose vitamin C versus the standard therapy group (HR=0.14, 95% CI, 0.03-0.72). Oxygen support status was improved more with high-dose vitamin C than standard therapy (63.9% vs 36.1%). No safety events were associated with high-dose vitamin C therapy. CONCLUSION: High-dose vitamin C may reduce the mortality and improve oxygen support status in patients with Coronavirus disease 2019 without adverse events.


Assuntos
Ácido Ascórbico/uso terapêutico , COVID-19/tratamento farmacológico , Vitaminas/uso terapêutico , Idoso , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/efeitos adversos , COVID-19/diagnóstico , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação , Resultado do Tratamento , Vitaminas/administração & dosagem , Vitaminas/efeitos adversos
20.
JAMA ; 325(8): 742-750, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33620405

RESUMO

Importance: Sepsis is a common syndrome with substantial morbidity and mortality. A combination of vitamin C, thiamine, and corticosteroids has been proposed as a potential treatment for patients with sepsis. Objective: To determine whether a combination of vitamin C, thiamine, and hydrocortisone every 6 hours increases ventilator- and vasopressor-free days compared with placebo in patients with sepsis. Design, Setting, and Participants: Multicenter, randomized, double-blind, adaptive-sample-size, placebo-controlled trial conducted in adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction. Participants were enrolled in the emergency departments or intensive care units at 43 hospitals in the United States between August 2018 and July 2019. After enrollment of 501 participants, funding was withheld, leading to an administrative termination of the trial. All study-related follow-up was completed by January 2020. Interventions: Participants were randomized to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 hours (n = 252) or matching placebo (n = 249) for 96 hours or until discharge from the intensive care unit or death. Participants could be treated with open-label corticosteroids by the clinical team, with study hydrocortisone or matching placebo withheld if the total daily dose was greater or equal to the equivalent of 200 mg of hydrocortisone. Main Outcomes and Measures: The primary outcome was the number of consecutive ventilator- and vasopressor-free days in the first 30 days following the day of randomization. The key secondary outcome was 30-day mortality. Results: Among 501 participants randomized (median age, 62 [interquartile range {IQR}, 50-70] years; 46% female; 30% Black; median Acute Physiology and Chronic Health Evaluation II score, 27 [IQR, 20.8-33.0]; median Sequential Organ Failure Assessment score, 9 [IQR, 7-12]), all completed the trial. Open-label corticosteroids were prescribed to 33% and 32% of the intervention and control groups, respectively. Ventilator- and vasopressor-free days were a median of 25 days (IQR, 0-29 days) in the intervention group and 26 days (IQR, 0-28 days) in the placebo group, with a median difference of -1 day (95% CI, -4 to 2 days; P = .85). Thirty-day mortality was 22% in the intervention group and 24% in the placebo group. Conclusions and Relevance: Among critically ill patients with sepsis, treatment with vitamin C, thiamine, and hydrocortisone, compared with placebo, did not significantly increase ventilator- and vasopressor-free days within 30 days. However, the trial was terminated early for administrative reasons and may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03509350.


Assuntos
Anti-Inflamatórios/uso terapêutico , Ácido Ascórbico/uso terapêutico , Hidrocortisona/uso terapêutico , Respiração Artificial , Sepse/tratamento farmacológico , Tiamina/uso terapêutico , Vitaminas/uso terapêutico , Adulto , Idoso , Estado Terminal , Método Duplo-Cego , Quimioterapia Combinada , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Sepse/complicações , Sepse/mortalidade , Sepse/terapia , Resultado do Tratamento , Vasoconstritores/uso terapêutico
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