The effectiveness of nano-curcumin on patients with COVID-19: A systematic review of clinical trials.

The main aim of the current study was to summarize the findings of available clinical studies to assess nano-curcumin's influence on COVID patients. A comprehensive online search was performed in Scopus, PubMed, ISI Web of Science, and Google Scholar until March 2022 to identify trials that investigated the effects of nano-curcumin in patients with COVID-19. Eight studies comprising 569 patients were included in this review. Compared with placebo, nano-curcumin had no significant effect on C-reactive protein (CRP) and high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). However, gene expression of IL-6 and gene expression as well as secretion of interleukin-1 beta (IL-1ß) significantly decreased following nano-curcumin intervention. Nano-curcumin had beneficial effects on fever, cough, chills, myalgia, and olfactory and taste disturbances. The duration of hospitalization and mortality rate were significantly lower in the nano-curcumin group compared with the control group. Lymphocyte count was significantly increased after curcumin supplementation. Nano-curcumin also had favorable effects on O2 saturation, sputum, chest pain, wheeze, and dyspnea in patients with COVID-19. No major adverse effects were reported in response to nano-curcumin supplementation. In summary, the results of this systematic review of clinical trials suggested that nano-curcumin supplementation has beneficial effects on inflammation, respiratory function, disease manifestations, and complications in patients with COVID-19 viral infection.

Curcumin-piperine co-supplementation and human health: A comprehensive review of preclinical and clinical studies.

Curcumin is extracted from the rhizomes Curcuma longa L. It is known for its anti-inflammatory and anti-oxidant activities. Despite its safety and potential for use against various diseases, curcumin's utility is restricted due to its low oral bioavailability. Co-administration of curcumin along with piperine could potentially improve the bioavailability of curcumin. The present review aimed to provide an overview of the efficacy and safety of curcumin-piperine co-supplementation in human health. The findings of this comprehensive review show the beneficial effects of curcumin-piperine in improving glycemic indices, lipid profile and antioxidant status in diabetes, improving the inflammatory status caused by obesity and metabolic syndrome, reducing oxidative stress and depression in chronic stress and neurological disorders, also improving chronic respiratory diseases, asthma and COVID-19. Further high-quality clinical trial studies are needed to firmly establish the clinical efficacy of the curcumin-piperine supplement.

Effect of nano-curcumin on various diseases: A comprehensive review of clinical trials.

The antioxidant, anti-inflammatory, and antibacterial properties of curcumin have made it a valuable herbal product for improving various disorders, such as COVID-19, cancer, depression, anxiety, osteoarthritis, migraine, and diabetes. Recent research has demonstrated that encapsulating curcumin in nanoparticles might improve its therapeutic effects and bioavailability. To our knowledge, the efficacy of nano-curcumin on different aspects of health and disease has not been summarized in a study. Therefore, this review aimed to evaluate nano-curcumin's efficacy in various diseases based on the findings of clinical trials. In order to review publications focusing on nanocurcumin's impact on various diseases, four databases were searched, including PubMed, Scopus, Web of Science, and Google Scholar. This review highlights the potential benefits of nano-curcumin in improving a wide range of human diseases including COVID-19, neurological disorders, chronic disease, oral diseases, osteoarthritis, metabolic syndrome, and other diseases, especially as an adjunct to standard therapy and a healthy lifestyle.

Evaluation of the effectiveness of the modified nutrition risk in the critically ill (mNUTRIC) score in critically ill patients affected by COVID-19 admitted to the intensive care unit (ICU).

BACKGROUND: COVID-19 is a very harmful pandemic, and its recovery process is highly influenced by nutritional status; however, an appropriate nutritional scale has not yet been proposed for these patients. Therefore, the purpose of this study was to evaluate the effectiveness of the modified Nutrition Risk in the Critically ill (mNUTRIC) score in critically ill patients affected by COVID-19 admitted to the intensive care unit (ICU). MATERIAL AND METHODS: This was a cross-sectional study performed on 204 critically ill patients affected by COVID-19 admitted to the ICU wards. Evaluated indicators include the mNUTRIC Score as well as demographic, and biochemical indicators. RESULTS: A high percentage of COVID-19 patients (67.2%) had severe disease. Hospital and ICU stay (p > 0.001) and PH (p > 0.001) values were significantly lower in non-survivors than in survivors. mNUTRIC score (p > 0.001), PCO2 (p = 0.003), and CRP levels (p = 0.021) were significantly higher in non-survivors than survivors. mNUTRIC score had a direct correlation with age (p > 0.001), AST (p = 0.000), LDH (p = 0.026), and CRP (p = 0.014) and an inverse correlation with hospital duration (p = 0.031), albumin (p = 0.003) and PH (p < 0.001). Furthermore, there was a non-significant correlation between the mNUTRIC score and mortality chance (OR = 1.085, 95%CI [0.83, 1.42], p = 0.552). While, patients with more severe COVID-19 disease (OR = 8.057, 95%CI [1.33, 48.64], p = 0.023) and higher PCO2 (OR = 1.042, 95%CI [1.01, 1.08], p = 0.023) levels had higher odds of mortality. CONCLUSIONS: Our findings revealed that COVID-19 patients with higher CRP levels and lower PH had higher mortality and poor nutritional condition. Moreover, there was a non-significant association between the mNUTRIC score and mortality chance.

The effects of adjunctive treatment with L-carnitine on monitoring laboratory variables in ICU patients: a double-blinded randomized controlled clinical trial.

BACKGROUND: Critically ill patients must be monitored constantly in intensive care units (ICUs). Among many laboratory variables, nutritional status indicators are a key role in the prognosis of diseases. We investigated the effects of L-carnitine adjunctive therapy on monitoring variables in critical illness. METHOD: A prospective, double-blind, randomized controlled trial was implemented in a medical ICU. Participants were 54 patients, aged > 18 years, with multiple conditions, randomly assigned to receive 3 g L-carnitine per day or placebo, along with enteral feeding, for 1 week. Primary outcomes included monitoring variables related to nutritional status. RESULT: Of 54 patients randomly assigned, 51 completed the trial. Serum albumin (Alb) (P-value: 0.001), total protein (P-value: 0.003), and calcium (Ca) (0.044) significantly increased in the intervention vs. control group. Alanine transaminase (ALT) (0.022), lactate (<0.001), creatinine (Cr) (0.005), and international normalized ratio (INR) (0.049) decreased meaningfully in the intervention vs. control group. CONCLUSION: L-Carnitine supplementation in critically ill patients can improve several parameters including INR, Cr, ALT, lactate, Ca, Alb, and total protein. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT 20151108024938N2. This trial was approved by the Research Ethics Committee of Mashhad University of Medical Sciences (registration code: IR.MUMS.fm.REC.1396.671) (available at https://en.irct.ir/trial/30748 , May 2018).

The efficacy of curcumin-piperine co-supplementation on clinical symptoms, duration, severity, and inflammatory factors in COVID-19 outpatients: a randomized double-blind, placebo-controlled trial.

BACKGROUND: COVID-19 pandemic has made the disease a major global problem by creating a significant burden on health, economic, and social status. To date, there are no effective and approved medications for this disease. Curcumin as an anti-inflammatory agent can have a positive effect on the control of COVID-19 complications. This study aimed to assess the efficacy of curcumin-piperine supplementation on clinical symptoms, duration, severity, and inflammatory factors in patients with COVID-19. METHODS: Forty-six outpatients with COVID-19 disease were randomly allocated to receive two capsules of curcumin-piperine; each capsule contained 500 mg curcumin plus 5 mg piperine or placebo for 14 days. RESULTS: Mean changes in complete blood count, liver enzymes, blood glucose levels, lipid parameters, kidney function, and c-reactive protein (CRP) were not significantly different between the two groups. There was a significant improvement in health status, including dry cough, sputum cough, ague, sore throat, weakness, muscular pain, headache, and dyspnea at week 2 in both curcumin-piperine and placebo groups (P value < 0.05); however, the improvement in weakness was more in the curcumin-piperine group than with placebo group (P value 025). CONCLUSION: The present study results showed that curcumin-piperine co-supplementation in outpatients with COVID-19 could significantly reduce weakness. However, in this study, curcumin-piperine co-supplementation could not significantly affect the other indices, including biochemical and clinical indices. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20121216011763N46 . 2020-10-31.

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.

Evaluation of the effectiveness of the Nutritional Risk Screening System 2002 (NRS-2002) in COVID-19 patients admitted to the intensive care unit.

BACKGROUND: Nutritional status of patients with COVID-19 can affect the recovery process of patients; however, no nutritional scale was introduced to evaluate the nutritional status of the patients. Thus, the main objective of this study was to examine the usefulness of Nutritional status-2002 (NRS-2002) among COVID-19 patients admitted to the intensive care unit (ICU). MATERIAL AND METHODS: In this cross-sectional study, 73 patients with definitive corona diagnosis admitted to the ICUs of Al-Zahra hospital, Isfahan, Iran in October 2020 to January 2021 were recruited. Dietary intake, NRS-2002, demographic, anthropometric and biochemical indices of patients were recorded. RESULTS: The majority of patients were at risk for moderate (69.9%) to severe (12.3%) malnutrition. Daily calorie intake (P = .001) and albumin (P = .001) levels in deceased patients were significantly lower than the recovered group. A direct correlation between NRS-2002 and age (P < .001) and an inverse correlation with daily calorie intake (P = .002), albumin (P = .05) and PaO2 (P = .034) was found. Moreover, there is a strong correlation between NRS-2002 score and chance of death among COVID-19 patients (OR=34.5, 95%CI:(5.2 - 228.93), P-value<0.001). Likewise, the levels of bilirubin direct (OR=8, 95%CI:(1.30 - 49.38), P-value=0.025) and creatine-phosphokinase (OR=0.9, 95%CI:(0.99 - 1.00), P-value=0.035) have a significant direct association with chance of death. CONCLUSION: Results showed patients with COVID-19 admitted to the ICU did not have appropriate nutritional status and mortality was higher among patients with lower amounts of the serum albumin and daily calorie intakes. Furthermore, there is a strong association between the NRS-2002 index and the chance of mortality in these patients.

Curcumin and Piperine in COVID-19: A Promising Duo to the Rescue?

COVID-19 is now pandemic throughout the world, and scientists are searching for effective therapies to prevent or treat the disease. The combination of curcumin and piperine is a potential option for the management of COVID-19 based on several mechanisms including antiviral, anti-inflammatory, immunomodulatory, antifibrotic, and antioxidant effects. Here, we describe the probable mechanism of curcumin-piperine against COVID-19. Administration of curcumin-piperine combination appears as a potential strategy to counterbalance the pathophysiological features of COVID-19 including inflammation. The optimal dose and duration of curcumin-piperine supplementation should be determined in the future.

Cinnamon: A Promising Natural Product Against COVID-19.

COVID-19 is a pandemic and acute respiratory disease. Every day, all around the world, researchers are endeavoring to find effective or potential adjuvant therapies. Studies illustrate that essential oils from cinnamon and derivatives such as cinnamaldehyde and cinnamic acid possess numerous biological activities. In this paper, we have reviewed the possible mechanisms of cinnamon on the inflammatory cascade as a potential alternative therapy to decrease oxidative stress and inflammation in COVID-19 patients.

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.

Effects of curcumin-piperine co-supplementation on clinical signs, duration, severity, and inflammatory factors in patients with COVID-19: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: This study aims to investigate the efficacy of curcumin-piperine co-supplementation on disease duration, severity and clinical symptoms, and inflammatory mediators in patients with coronavirus (COVID-19). TRIAL DESIGN: This is a randomized, placebo-controlled, double-blind, parallel arm clinical trial. PARTICIPANTS: All patients aged 20-75 years with the diagnosis of Covid-19 based on the PCR test. The exclusion criteria will include an age less than 20 and more than 75 years, current use of warfarin or other anticoagulant drugs, and the presence of sensitivity to herbal products such as turmeric and pepper. This study will be conducted in academic hospitals affiliated to Isfahan University of Medical Sciences, Isfahan, Iran. INTERVENTION AND COMPARATOR: Fifty outpatients will be randomly allocated in a ratio of 1:1 to receive a capsule of curcumin-piperine containing 500 mg curcumin plus 5 mg piperine or matching placebo containing 505 mg maltodextrin twice a daily, after lunch and dinner, over a period of 2 weeks. Similarly, 50 inpatients who are admitted to hospital wards excluding intensive care unit (ICU) will be randomly assigned in a ratio of 1:1 to receive a capsule curcumin-piperine or matching placebo (provided by the Sami Labs company) twice a daily, after lunch and dinner, over a period of 2 weeks. MAIN OUTCOMES: The main outcomes of this study are the efficacy of curcumin-piperine on coronavirus disease's clinical symptoms, duration, severity, and inflammatory mediators after 2 weeks of curcumin-piperine co-supplementation. RANDOMISATION: Randomization sequences will be generated with the use of a random-number table with a permuted block design (block size of 4) and stratification according to the gender variable (male vs. female). These sequences will be prepared by an independent statistician and will be kept in opaque, sealed, numbered envelopes which will be opened only at the time of enrollment. The allocation ratio in intervention and control groups is 1:1. Researchers and all patients will be unaware of the study-group assignment until the completion of data analyses. BLINDING (MASKING): This study is a double-blind clinical trial (participant, researcher). The curcumin-piperine and placebo supplements are packaged in similar numbered drug containers, and the researcher and all patients will be unaware of the study assignment until the end of the study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The calculated total sample size is 100 patients, with 25 patients in each group. TRIAL STATUS: The protocol is Version 2.0, May 24, 2020. Recruitment began May 4, 2020, and is anticipated to be completed by April 19, 2021. TRIAL REGISTRATION: This trial has been registered by the title of "Effect of curcumin-piperine co-supplementation on disease duration, severity and clinical signs, and inflammatory factors in patients with coronavirus (COVID-19): A randomized, double-blind, placebo-controlled clinical trial study" in the Iranian Registry of Clinical Trials (IRCT) with code "IRCT20121216011763N46", https://www.irct.ir/trial/47529 . The registration date is May 4, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting 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 effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: This study aims to assess the effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19). TRIAL DESIGN: This is a Double-Blind, Placebo-Controlled, Parallel Arm, Randomized Phase ΙΙ Clinical Trial. PARTICIPANTS: Patients with the confirmed COVID-19 based on the PCR test are eligible to participate in the trial if they are 18 to 75 years of age and have no history of the current use of warfarin or propolis supplement and presence of sensitivity to bee products. Patients will be recruited from the Al-Zahra hospital in Isfahan city, Isfahan, Iran. INTERVENTION AND COMPARATOR: Participants (N=40) in the intervention group will receive an identical propolis tablet (containing 300 mg Iranian green propolis extract) three times a day for a period of 2 weeks. Participants (N=40) in the control group will receive an identical placebo tablet (containing 300 mg microcrystalline cellulose) three times a day for 2 weeks. All tablets are prepared by the Reyhan Naghsh Jahan Pharmaceutical Co., Isfahan, Iran. MAIN OUTCOMES: The main outcomes are changes in the coronavirus disease's clinical symptoms including duration and severity from baseline to the end of 2 weeks. RANDOMIZATION: Eligible patients will be randomly allocated in a 1:1 ratio to the intervention or control group. Randomization will be performed on the basis of permuted block sizes of 4 and will be stratified according to sex categories. Randomization sequences will be prepared by the trial's pharmacist with the use of random-number tables. BLINDING (MASKING): The trial-group assignment will be concealed from all participants, clinicians, and investigators throughout the trial. To ensure blinding, randomization sequences will be kept in identical, opaque, sealed, sequentially numbered envelopes. Only the trial's pharmacist has access to the randomization list. Also, the placebo tablet will be similar to the propolis tablet in terms of texture, taste, color, odor, and weight. Both tablets will be provided in containers that are completely identical in weight, shape, labelling, and packaging. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The calculated total sample size is 80 patients, with 40 patients in each group. TRIAL STATUS: The protocol is Version 1.0, October 10, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by March 21, 2021. TRIAL REGISTRATION: The name of the trial register: The effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19): A randomized, double-blind, placebo-controlled clinical trial. IRCT registration number: IRCT20200802048267N1 . Date of trial registration: 20 October 2020, retrospectively registered. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional 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.