The effects of L-carnitine supplementation on inflammation, oxidative stress, and clinical outcomes in critically Ill patients with sepsis: a randomized, double-blind, controlled trial.

BACKGROUND: Sepsis, a life-threatening organ dysfunction caused by a host's dysregulated response to infection with an inflammatory process, becomes a real challenge for the healthcare systems. L-carnitine (LC) has antioxidant and anti-inflammatory properties as in previous studies. Thus, we aimed to determine the effects of LC on inflammation, oxidative stress, and clinical parameters in critically ill septic patients. METHODS: A randomized double-blinded controlled trial was conducted. A total of 60 patients were randomized to receive LC (3 g/day, n = 30) or placebo (n = 30) for 7 days. Inflammatory and oxidative stress parameters (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), superoxide dismutase (SOD), malondialdehyde (MDA), total antioxidant capacity (TAC), 28-day mortality rate, and some monitoring variables were evaluated. RESULTS: There was no statistically significant difference between study arms in baseline characteristics and disease severity scores. CRP (p < 0.001) and ESR (p: 0.004) significantly reduced, and SOD (p < 0.001) and TAC (p < 0.001) significantly improved in the LC group after 7 days. Between-group analysis revealed a significant reduction in CRP (p: 0.001) and serum chloride (p: 0.032), an increase in serum albumin (p: 0.036) and platelet (p: 0.004) significantly, and an increase in SOD marginally (p: 0.073). The 28-day mortality rate was also lower in the LC group compared with placebo (7 persons vs. 15 persons) significantly (odds ratio: 0.233, p: 0.010). CONCLUSIONS: L-carnitine ameliorated inflammation, enhanced antioxidant defense, reduced mortality, and improved some clinical outcomes in critically ill patients with sepsis. TRIAL REGISTRATION: IRCT20201129049534N1; May 2021.

Evaluation of Curcumin-Piperine Supplementation in COVID-19 Patients Admitted to the Intensive Care: A Double-Blind, Randomized Controlled Trial.

BACKGROUND: Curcumin is a traditional remedy for diseases associated with hyper-inflammatory responses and immune system impairment. Piperine, a bioactive compound in black pepper, has the potential to enhance curcumin bioavailability. 0This study aims to examine the effect of the curcumin-piperine co-supplementation in patients infected with SARS-CoV-2 and admitted to the intensive care unit (ICU). MATERIAL AND METHODS: In this parallel randomized, double-blind, placebo-controlled trial, 40 patients with COVID-19 admitted to ICU were randomized to receive three capsules of curcumin (500 mg)-piperine (5 mg) or placebo for 7 days. RESULTS: After 1 week of the intervention, serum aspartate aminotransferase (AST) (p = 0.02) and C-reactive protein (CRP) (p = 0.03) were significantly decreased, and hemoglobin was increased (p = 0.03) in the curcumin-piperine compared to the placebo group. However, compared with the placebo, curcumin-piperine had no significant effects on the other biochemical, hematological, and arterial blood gas and 28-day mortality rate was three patients in each group (p = 0.99). CONCLUSION: The study results showed that short-term curcumin-piperine supplementation significantly decreased CRP, AST, and increased hemoglobin in COVID-19 patients admitted to the ICU. Based on these promising findings, curcumin appears to be a complementary treatment option for COVID-19 patients, although some parameters were not affected by the intervention.

The effects of L-carnitine supplementation on inflammatory factors, oxidative stress, and clinical outcomes in patients with sepsis admitted to the intensive care unit (ICU): study protocol for a double blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Sepsis is a common cause for admission to the intensive care unit (ICU), and its incidence has been increasing. It is associated with a significant increase in serum inflammatory biomarkers such as C-reactive protein (CRP) and cytokines such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF). Sepsis is also associated with pathophysiological changes that include fluid accumulation in the lungs, eventually leading to acute respiratory distress syndrome (ARDS), tissue edema, hypotension, and acute kidney injury (AKI). Conventional therapies include antibiotics, but these may have important adverse effects, so novel therapeutic approaches are required. In animal studies, L-carnitine improves antioxidant status, and in some clinical trials, it has been shown to reduce inflammation. It has also been shown to improve respiratory distress and help maintain coenzyme A homeostasis, metabolic flexibility, promoting the normal function of the tricarboxylic acid (TCA) cycle, and oxidation of fatty acids by peroxisomes. We aim to determine the effects of very high doses of L-carnitine on inflammatory factors, oxidative stress, and clinical outcomes of patients with sepsis in ICU. METHOD AND DESIGN: In this double-blind, randomized controlled clinical trial, we will use block randomization of 60 patients with sepsis, aged between 20 and 65 years from Al-Zahra Hospital, Isfahan, Iran. The intervention group (n = 30) will receive three capsules of L-carnitine (each capsule contains 1000 mg L-carnitine; totally 3000 mg/day) for 7 days, and a control group (n = 30) will receive a placebo with the same dose and for the same duration in addition to usual care. At baseline, scores for clinical and nutritional status (Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), and NUTRIC Score) will be assessed. At beginning and end point of the study, inflammatory markers (CRP, erythrocyte sedimentation rate (ESR)), oxidative stress status (total oxidative stress (TOS), total antioxidant capacity (TAC)), and clinical variables will be evaluated also. The mortality rate will be assessed within 28 days of the beginning of the intervention. DISCUSSION: Because of the anti-inflammatory and antioxidant properties of L-carnitine, it is possible that using a high dose of 3000 mg daily of this nutritional supplement may reduce inflammation and oxidative stress and improve subsequent mortality of critically ill patients with sepsis. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20201129049534N1 . Registered on 2 May 2021.

The clinical use of curcumin on neurological disorders: An updated systematic review of clinical trials.

Neuroprotective effects of curcumin have been shown in previous studies. This updated systematic review of clinical trials aimed to investigate the effect of curcumin on neurological disorders. Databases including PubMed, Scopus, Web of Science, and Google Scholar were systematically searched to identify clinical trials investigating the effects of curcumin/turmeric supplements alone, or in combination with other ingredients, on neurological diseases. Nineteen studies comprising 1,130 patients met the inclusion criteria. Generally, intervention and study outcomes were heterogeneous. In most of the studies, curcumin had a favorable effect on oxidative stress and inflammation. However, with the exception of AD, curcumin supplementation either alone, or in combination with other ingredients, had beneficial effects on clinical outcomes for the other aforementioned neurodegenerative diseases. For example, the frequency, severity, and duration of migraine attacks, scores on the revised ALS functional rating scale, and the occurrence of motor complications in PD were all significantly improved with curcumin supplementation either alone or in combination with other ingredients. However, in three studies, several adverse side effects (mostly gastrointestinal in nature) were reported. Curcumin supplementation may have favorable effects on inflammatory status and clinical outcomes of patients with neurological disease, although the results were not consistent.

Curcumin for the Treatment of Prostate Diseases: A Systematic Review of Controlled Clinical Trials.

Prostate cancer is one of the significant causes of morbidity and mortality worldwide. Benign prostatic hyperplasia is another condition of the prostate which, like prostate cancer, is more common among ageing men and is linked to inflammation. In this study, a systematic review was undertaken to estimate the effect of turmeric or curcumin supplementation on prostate diseases. A comprehensive search was conducted in PubMed, Scopus, ISI Web of Science and Google Scholar up to 15 April 2020 to identify clinical trials assessing the effects of curcumin/turmeric alone or in combination with other herbs on prostate diseases. This led to the identification of 11 records comprising 745 patients who met the eligibility criteria. Eight studies were conducted on patients with prostate cancer, and three were on other diseases of the prostate. Although outcomes across the studies were heterogeneous, in some studies curcumin/turmeric supplementation had some favourable effects. This included beneficial effects on the levels of prostate-specific antigen (PSA) (2/6 studies), quality of life (1/2 studies), as well as on oxidative stress markers, feelings of incomplete bladder emptying, urination frequency, intermittency, urgency, weak stream, straining and nocturia. Curcumin/turmeric supplementation had no significant adverse effects among patients. This study demonstrated that turmeric or curcumin supplementation might have beneficial effects on some parameters related to prostate diseases, but it should be noted that some studies showed no effect. Therefore, further studies using curcumin-related compounds, particularly in highly bioavailable forms, are needed to assess the impact of curcumin on prostate conditions.

Effect of curcumin-pipeine supplementation on clinical status, mortality rate, oxidative stress, and inflammatory markers in critically ill ICU patients with COVID-19: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This study aims to investigate the efficacy of curcumin-piperine co-supplementation on oxidative stress factors, clinical symptoms, and mortality rate in patients with coronavirus (COVID-19) admitted to the intensive care unit (ICU). TRIAL DESIGN: This study is a randomized, placebo-controlled, double-blind, parallel-arm clinical trial. PARTICIPANTS: The study participants will be recruited from patients admitted to the ICU of Al-Zahra hospital with a definitive diagnosis of COVID-19. The inclusion criteria are aged between 20 and 75 years, confirmation of COVID-19 based on the PCR test, and admitted to the ICU. The exclusion criteria include the present use of parenteral nutrition support, a history of underlying diseases such as congenital disorders, immune diseases, renal and hepatic insufficiency, and pancreatitis, a history of sensitivity to herbal remedies such as turmeric and pepper, and regular use of anticoagulant drugs such as warfarin. This study will be performed in the Al-Zahra hospital, an academic hospital affiliated with Isfahan University of Medical Sciences, Isfahan, Iran. INTERVENTION AND COMPARATOR: Sixty eligible patients will be randomly assigned, in a 1:1 ratio, to receive curcumin-piperine capsules (three capsules/day; each capsules containing 500 mg curcumin plus 5 mg piperine; in total 1500 mg curcumin and 15 mg piperine/daily) for seven days (n=30) or matching placebo capsules (three capsules/day; each capsules containing 505 mg maltodextrin; totally 1515 mg, maltodextrin/ daily) for same duration (n=30). Capsules will be administered after oral or enteral feeding at 9, 15 and 21 o'clock. MAIN OUTCOMES: The primary outcome is the time from initiation of supplementation (curcumin-piperine or placebo) to normalization of fever, respiratory rate, and blood oxygen saturation. The secondary outcomes are the mortality rate, length of stay in ICU, temperature, levels of blood oxygen saturation, ventilator dependency, respiratory rate, levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), levels of liver markers (ALT, AST, LDH), and levels of kidney function markers (BUN, Creatinine). FOLLOW UP: All of the parameters will be assessed at baseline and end of the study (7 days intervention). In addition, the rate of mortality will be collected after 4 weeks (28 days' mortality in the ICU, 4 weeks follow up). RANDOMISATION: Eligible patients will be randomly assigned to either the intervention group (Curcumin-piperine) or the control group (Placebo). Randomization sequences will be generated using an electronic table of random numbers to allocate the included participants into either control or intervention groups (in a 1:1 ratio) using the stratified block randomization method. Stratification was conducted according to sex (male and female), with a block size of four. The allocation sequences will be prepared by an independent statistician and will be kept inside sealed, opaque, and consecutively numbered envelopes. Participants, investigators, nurses, and physicians will be unaware of the trial-group assignment. BLINDING (MASKING): This study is a double-blind clinical trial (participants, investigators, nurses, and physicians). The curcumin-piperine and placebo supplements will be similar in the terms of texture, taste, color, odor, and weight. Both tablets will be provided in containers that are completely identical in weight, shape, labeling, and packaging. All participants, investigators, nurses, and physicians will be unaware of the trial-group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is estimated at 60 participants, including 30 patients in the intervention group and 30 patients in the placebo group. TRIAL STATUS: The protocol is Version 2, registered on May 13, 2021. Recruitment began May 20, 2021, and is anticipated to be completed by September 20, 2021. TRIAL REGISTRATION: This trial has been registered in Iranian Registry of Clinical Trials (IRCT) with the title of "Evaluation of the effect of curcumin-piperine supplementation in patients with coronavirus admitted to the intensive care unit (ICU): a double-blind clinical trial study". IRCT registration number is IRCT20121216011763N52 . The registration date was May 13, 2021. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (File 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

The role of phytochemicals in sepsis: A mechanistic and therapeutic perspective.

Sepsis and septic shock are still a leading cause of mortality and morbidity in intensive care units worldwide. Sepsis is an uncontrolled and excessive response of the innate immune system toward the invading infectious microbes, characterized by the hyper-production of pro-inflammatory mediators such as interleukin (IL)-1ß, IL-6, tumor-necrosis factor (TNF)-α, and high-mobility group box 1 (HMGB1). In severe sepsis, the overwhelming production of pro-inflammatory cytokines and reactive oxygen species may compromise organ function and lead to the induction of abnormal apoptosis in different organs, resulting in multiple organ dysfunction syndrome and death. Hence, compounds that are able to attenuate inflammatory responses may have therapeutic potential for sepsis treatment. Understanding the pathophysiology and underlying molecular mechanisms of sepsis may provide useful insights in the discovery and development of new effective therapeutics. Therefore, numerous studies have invested much effort into elucidating the mechanisms involved with the onset and development of sepsis. The present review mainly focuses on the molecules and signaling pathways involved in the pathogenicity of sepsis. Additionally, several well-known natural bioactive herbal compounds and phytochemicals, which have shown protective and therapeutic effects with regard to sepsis, as well as their mechanisms of action, are presented. This review suggests that these phytochemicals are able to attenuate the overwhelming inflammatory responses developed during sepsis by modulating different signaling pathways. Moreover, the anti-inflammatory and cytoprotective activities of phytochemicals make them potent compounds to be included as complementary therapeutic agents in the diets of patients suffering from sepsis in an effort to alleviate sepsis and its life-threatening complications, such as multi-organ failure.

Evaluation of the effect of curcumin on pneumonia: A systematic review of preclinical studies.

Pneumonia is a major cause of morbidity and mortality worldwide and causes a significant burden on the healthcare systems. Curcumin is a natural phytochemical with anti-inflammatory and anti-neoplastic characteristics. The aim of this study was to conduct a systematic review of published studies on the effect of curcumin on preclinical models of pneumonia. A comprehensive search was conducted in PubMed/Medline, Scopus, Web of Science and Google Scholar from inception up to March 1, 2020 to recognize experimental or clinical trials assessing the effects of curcumin on pneumonia. We identified 17 primary citations that evaluated the effects of curcumin on pneumonia. Ten (58.8%) studies evaluated the effect of curcumin on mouse models of pneumonia, generated by intranasal inoculation of viruses or bacteria. Seven (41.2%) studies evaluated the inhibitory effects of curcumin on the pneumonia-inducing bacteria. Our results demonstrated that curcumin ameliorated the pneumonia-induced lung injury, mainly through a reduction of the activity and infiltration of neutrophils and the inhibition of inflammatory response in mouse models. Curcumin ameliorates the severity of pneumonia through a reduction in neutrophil infiltration and by amelioration of the exaggerated immune response in preclinical pneumonia models.