Nutritional factors and physical frailty: Highlighting the role of functional nutrients in the prevention and treatment.

Physical frailty, an age-related decline in the physiological capacity and function of various organs, is associated with higher vulnerability to unfavorable health outcomes. The mechanisms proposed for physical frailty including increased inflammation and oxidative stress are closely related to nutritional status. In addition to traditional nutritional factors such as protein malnutrition and nutrient deficiencies, emerging evidence has focused on the role of functional nutrients including polyphenols, carotenoids, probiotics, prebiotics, omega-3 long-chain polyunsaturated fatty acids (n-3 PUFAs), ß-hydroxy-ß-methylbutyrate (HMB), coenzyme Q10 (CoQ10), and L-carnitine in modifying the risk of physical frailty syndrome. Although several clinical trials have suggested the beneficial effects of supplementation with polyphenols, HMB, and prebiotics on frailty indices, the current evidence is still not robust to support recommendations on the routine clinical use of such functional nutrients for the management of frailty. Similarly, the association between CoQ10 and frailty was mainly assessed in observational studies, and more randomized controlled trials are needed in this regard. A limited number of studies have reported the beneficial effect of L-carnitine supplementation on frailty indices. Since carnitine is mainly found in skeletal muscle and its measurement is thus challenging due to ethical constraints, it is necessary to examine the effect of different doses of L-carnitine on frailty and its indices in future studies. A large number of interventional studies evaluated the impact of n-3 PUFA supplementation on physical frailty in the elderly and many of them reported improved physical performance following supplementation, especially when combined with resistance training programs. Although promising findings from experimental and observational studies have been reported on functional nutrients, high-quality evidence from randomized controlled trials as well as detailed mechanistic studies are still required to affirm their role in the prevention and/or treatment of physical frailty. This review aims to describe the current state of research on functional nutrients that may modify the development or prognosis of frailty syndrome.

The effectiveness of phytosomal curcumin on clinical and laboratory parameters of patients with multiple trauma admitted to the intensive care unit: a double-blind randomized placebo-controlled trial.

BACKGROUND: Multiple trauma has serious complications, which increases the risk of morbidity and mortality in the patients. This study aimed to evaluate the impact of supplementation with phytosomal curcumin on clinical and laboratory factors in critically ill patients with multiple trauma. METHODS: In this double-blind trial, 53 patients with multiple trauma, who were admitted to the intensive care unit (ICU) were randomized to receive either 2 capsules, each capsule containing 250 mg phytosomal (a total of 500 mg daily) as an intervention group or 2 identical capsules (placebo capsules), each containing 250 mg maltodextrin for 7 days. Clinical and laboratory were parameters assessed before and after the intervention. RESULTS: After seven days of intervention, the mean increase from baseline in the Glasgow coma scale (GCS) score was significantly higher in the curcumin compared with the placebo group (P-value: 0.028), while the reduction in the APACHE-II score in the curcumin group was greater than that the placebo group in a marginally non-significant fashion (P-value: 0.055). Serum total bilirubin (P-value: 0.036) and quantitative C-reactive protein (CRP) (P-value: 0.044) levels significantly decreased while potassium (P-value: 0.01) significantly increased in the curcumin compared with the placebo group. Moreover, supplementation with phytosomal curcumin significantly increased platelet count (P-value: 0.024) as compared with placebo. The 28-day mortality rate was 7.7% (n: 2 patients) and 3.7% (n: 1 patients) in the placebo and curcumin groups, respectively (P-value > 0.05). CONCLUSION: Phytosomal curcumin had beneficial effects on several clinical and laboratory factors including GCS, APACHEII, serum total bilirubin, CRP, and platelet count in ICU-admitted patients with multiple trauma. TRIAL REGISTRATION: IRCT20090306001747N1, Available on: https://www.irct.ir/trial/52692 . The first registration date was 12/01/2021.

The effect of curcumin-piperine supplementation on lipid profile, glycemic index, inflammation, and blood pressure in patients with type 2 diabetes mellitus and hypertriglyceridemia.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with insulin resistance and ensuing dysglycemia, dyslipidemia, and inflammation. Owing to the putative metabolic benefits of curcumin-piperine combination, we explored the efficacy of this combination in improving cardiometabolic indices of patients with T2DM and hypertriglyceridemia. In this double-blind clinical trial, 72 patients with T2DM and hypertriglyceridemia were randomized to receive either a tablet containing 500 mg of curcuminoids plus 5 mg of piperine, or a matched placebo for 12 weeks. Anthropometric indices, blood pressure, glycemic indices, lipid profile, C-reactive protein (CRP), quality of life, and mood were evaluated at baseline and end of the study. After 12 weeks of intervention, the levels of triglycerides (p-value = 0.001) and fasting blood glucose (p-value = 0.004) were significantly reduced in the curcumin-piperine compared with the placebo group. CRP levels were marginally reduced in the curcumin-piperine compared with the placebo group (p-value = 0.081). In addition, energy/fatigue significantly increased in the curcumin-piperine group compared to the control group (p-value = 0.024). However, between-group comparisons showed no significant change in other parameters, including anthropometric indices (waist circumference and body mass index (BMI)), biochemical parameters (low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c), and insulin), HOMA-IR, blood pressure, quality of life, and DASS-21 items between the studied groups (p-value >0.05). The current study showed that curcumin-piperine supplementation can improve serum CRP, triglycerides, and glucose concentrations in patients with T2DM and hypertriglyceridemia.

The effect of astaxanthin supplementation on inflammatory markers, oxidative stress indices, lipid profile, uric acid level, blood pressure, endothelial function, quality of life, and disease symptoms in heart failure subjects.

BACKGROUND: Heart failure is a chronic and progressive disease where the heart muscle is unable to pump enough blood and oxygen to meet the body's needs. Oxidative stress and inflammation are key elements in the development and progression of heart failure. Astaxanthin, a carotenoid, has strong anti-inflammatory and antioxidant effects that may protect the cardiovascular system. A study will evaluate the effect of astaxanthin supplementation on inflammatory status, oxidative stress, lipid profile, uric acid levels, endothelial function, quality of life, and disease symptoms in people with heart failure. METHODS: The current study is a double-blind controlled randomized clinical trial for 8 weeks, in which people with heart failure were randomly assigned to two groups: intervention (one capsule containing 20 mg of astaxanthin per day, n = 40) and placebo (one capsule containing 20 mg of maltodextrin per day, n = 40) will be divided. At the beginning and end of the intervention, uric acid, lipid profile, oxidative stress indices, inflammatory markers, blood pressure, nitric oxide, and anthropometric factors will be measured, and questionnaires measuring quality of life, fatigue intensity, shortness of breath, and appetite will be completed. SPSS version 22 software will be used for statistical analysis. DISCUSSION: There is a growing global interest in natural and functional food products. This RCT contributes to the expanding body of research on the potential benefits of astaxanthin in heart failure patients, including its antioxidant, lipid-lowering, and anti-inflammatory effects. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20200429047235N3. Registered on 26 March 2024.

Effect of dairy products fortified with vitamin d3 on restless legs syndrome in women with premenstrual syndrome, abdominal obesity and vitamin d deficiency: a pilot study.

BACKGROUNDS: Restless legs syndrome (RLS) is an unpleasant condition that affects the quality of life of patients. Its prevalence in increased in women with premenstrual syndrome (PMS). Vitamin D plays a key role in female reproduction through its impact on calcium homeostasis and neurotransmitters. We aimed to evaluate the effect of dairy products fortified with Vitamin D3 on RLS in women with PMS. MATERIALS AND METHODS: We conducted a 2.5-month, randomized, total-blinded clinical trial to evaluate the effectiveness of low-fat milk and yogurt fortified with vitamin D on RLS in women with PMS. Among 141 middle-aged women with abdominal obesity, 71 and 70 cases received fortified and non-fortified low-fat dairy products, respectively. All subjects completed a Symptoms Screening Tool (PSST) and RLS questionnaires. RESULTS: The results showed that in the women with severe PMS (PSST > 28), serum levels of vitamin D increased significantly following vitamin D fortification. The mean restless legs score in the severe PMS subgroup (PSST > 28) was significantly lower after the intervention (p < 0.05. Serum Vitamin D levels significantly differed between intervention and control groups in all individuals (PSST < 19, PSST 19-28, and PSST > 28) (p < 0.05), but no significant differences were found between RLS scores of the intervention and control groups in the three PMS subgroups (p > 0.05). CONCLUSION: Fortifying dairy products with vitamin D3 can increase the serum levels of vitamin D and reduce the RLS severity in women with severe PMS, but not in other groups.

Effects of cinnamon on anthropometric indices and headache-related disability of patients with migraine: A randomized double-blind placebo-controlled trial.

Objective: Increased body mass index (BMI) seems to be a risk factor for migraine attacks. Cinnamon has anti-inflammatory, neuroprotective, and anti-obesity effects. This study aimed to assess the effects of cinnamon on anthropometric indices and headache-related disability of patients with migraine. Materials and Methods: This study was conducted as a randomized, double-blind, placebo-controlled trial involving 50 migraine patients. Patients were randomized to receive either 600 mg cinnamon powder or placebo capsules for two months. Height, body weight (BW), waist circumference (WC), and hip circumference (HC) were measured.Furthermore, Minimal or Infrequent Disability (MIDAS) and Headache Daily Result (HDR) Questionnaires were recorded. Results: At the end of the treatment period, BW and BMI did not change in the intervention group; however, both factors were significantly increased in the placebo group (p=0.001). The change of WC, HDR and MIDAS was significantly different between the intervention and placebo groups (p<0.001). Furthermore, HC and WHR significantly decreased (p=0.001). Conclusion: Cinnamon seems to have beneficial effects on anthropometric indices and headache disability of migraine patients.

Evaluation of the effectiveness of curcumin and piperine co-supplementation on inflammatory factors, cardiac biomarkers, atrial fibrillation, and clinical outcomes after coronary artery bypass graft surgery.

BACKGROUND: Coronary artery bypass graft (CABG) is one of the preferred treatments for patients with heart problems, especially in individuals with other comorbidities and when multiple arteries are narrowed. This study aimed to assess the effects of administrating curcumin-piperine on patients who underwent CABG surgery. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial, in which 80 eligible adults who underwent CABG surgery, were randomized into 4 groups. Patients received 3 tablets daily for 5 days after the surgery, which contained curcumin-piperine (each tablet contained 500 mg curcumin +5 mg piperine) or a placebo (each tablet contained 505 mg maltodextrin). Group A received 3 placebo tablets, group B received 2 placebos and one curcumin-piperine tablet, group C received 1 placebo and 2 curcumin-piperine tablets, and group D received 3 curcumin-piperine tablets. Before and after the intervention, C-reactive protein (CRP), total antioxidant capacity (TAC), cardiometabolic factors, clinical outcomes, and 28-day mortality were evaluated. RESULTS: Between-group analysis showed that CRP significantly decreased (P = 0.028), and TAC significantly increased (P = 0.033) after the intervention (Post hoc analysis showed that for CRP, the difference was between group B and D, and for TAC was between group C and D). Between-group analysis also showed that creatine kinase mono-phosphate (CK-MB) marginally reduced (P = 0.077); however, changes for troponin I (P = 0.692), lactate dehydrogenase (LDH) (P = 0.668), ejection fraction (P = 0.340), and arterial fibrillation (P = 0.99) were not significant. Blood urea nitrogen (P = 0.820) and serum creatinine (P = 0.244) did not show notable changes between groups. CONCLUSION: Supplementation with curcumin-piperine had a promising effect on serum CRP and TAC. It also had a favorable impact on CK-MB among patients who underwent CABG surgery. TRIAL REGISTRATION: IRCT20201129049534N4, available on https://en.irct.ir/trial/56930.

The Association of Dietary Inflammatory Index and Cognitive Function in Iranian Elders.

BACKGROUND: Cognitive impairment is amongst the most substantial mental health problems in elderly people, and inflammation is an underlying mechanism for cognitive impairment. The dietary inflammatory index (DII®) reflects the overall inflammatory potential of individuals' diets. The current study aimed to assess the relationship between the DII and cognitive function among the Iranian old population. METHODS: This cross-sectional study was conducted on 221 subjects≥65 years old in healthcare centers in five socioeconomically distinct districts of Tehran, Iran. Dietary intake data were obtained using a validated food frequency questionnaire (FFQ). Energy-adjusted-DII (E-DIITM) scores were calculated for each participant according to a total of 35 food parameters, which were available from the FFQ. Mini mental state examination (MMSE), a brief screening questionnaire was used to assess cognitive function. RESULTS: E-DII scores were not significantly associated with cognitive function, both in the crude model (ß=-0.04, p-value=0.82) and after adjusting for potential confounders (ß=0.22, pvalue= 0.14). Additionally, in the unadjusted model, individuals in the highest tertile of E-DII score had increased odds of mild cognitive impairment (OR=1.13, p-trend=0.01) compared to those older adults in the lowest tertile of E-DII score. However, after controlling for potential confounders, these relationships faded (AOR=1.46, p-trend=0.12). CONCLUSION: The findings of the present study showed no significant relationship between E- DII and cognitive function among the Iranian elderly. Future prospective studies should be undertaken to explore the association between diet-associated inflammation and cognitive decline in the elderly.

Relationship Between Diabetes Mellitus and Periodontal/Peri-Implant Disease: A Contemporaneous Review.

The prevalence of diabetes mellitus (DM), a major chronic disease and a leading cause of death and disability around the world, is rising. According to the latest data, the global prevalence of DM has increased to 463 million (9.3% of adults) in 2019 and is estimated to reach 700 million by 2045. Periodontal disease, result of periodontium inflammation, is a common, chronic disease and has long been considered one of the complications of DM. Moreover, literature reflects a spectrum of conflicting viewpoints on the effect of diabetic conditions on the implant treatment strategies. The current review aims to update the recent epidemiologic evidence regarding the relationship between DM and periodontal/peri-implant disease, emphasising the effects of glycaemic control on the severity of these diseases and describing the pathobiological mechanisms underlying this association. This review's findings indicate a bidirectional relationship between DM and periodontal/peri-implant disease and that this relationship seems causal, implying that controlling these two diseases might help prevent each other's incidence. Additionally, the severity of periodontal/peri-implant disease is directly related to metabolic control. Although patients with diabetes can obtain implant success similar to those in systemically healthy individuals, an increased risk of peri-implantitis has been reported in DM patients. Therefore, the importance of glycaemic control and maintaining proper oral hygiene cannot be overstated.

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.

Effect of polyphenols against complications of COVID-19: current evidence and potential efficacy.

The COVID-19 pandemic that started in 2019 and resulted in significant morbidity and mortality continues to be a significant global health challenge, characterized by inflammation, oxidative stress, and immune system dysfunction.. Developing therapies for preventing or treating COVID-19 remains an important goal for pharmacology and drug development research. Polyphenols are effective against various viral infections and can be extracted and isolated from plants without losing their therapeutic potential. Researchers have developed methods for separating and isolating polyphenols from complex matrices. Polyphenols are effective in treating common viral infections, including COVID-19, and can also boost immunity. Polyphenolic-based antiviral medications can mitigate SARS-CoV-2 enzymes vital to virus replication and infection. Individual polyphenolic triterpenoids, flavonoids, anthraquinonoids, and tannins may also inhibit the SARS-CoV-2 protease. Polyphenol pharmacophore structures identified to date can explain their action and lead to the design of novel anti-COVID-19 compounds. Polyphenol-containing mixtures offer the advantages of a well-recognized safety profile with few known severe side effects. However, studies to date are limited, and further animal studies and randomized controlled trials are needed in future studies. The purpose of this study was to review and present the latest findings on the therapeutic impact of plant-derived polyphenols on COVID-19 infection and its complications. Exploring alternative approaches to traditional therapies could aid in developing novel drugs and remedies against coronavirus infection.

Coenzyme Q10 supplementation in burn patients: a double-blind placebo-controlled randomized clinical trial.

BACKGROUND: Burn injuries are important medical problems that, aside from skin damage, cause a systemic response including inflammation, oxidative stress, endocrine disorders, immune response, and hypermetabolic and catabolic responses which affect all the organs in the body. The aim of this study was to determine the effect of coenzyme Q10 (CoQ10) supplementation on inflammation, oxidative stress, and clinical outcomes in burn patients. METHODS: In a double-blind placebo-controlled randomized clinical trial, 60 burn patients were randomly assigned to receive 100 mg CoQ10 three times a day (total 300 mg/day) or a placebo for 10 days. Inflammatory markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), oxidative stress markers including total antioxidant capacity (TAC), malondialdehyde (MDA) and superoxide dismutase (SOD) activity, fasting blood glucose (FBG), blood urea nitrogen (BUN), creatinine, white blood cells (WBC), and body temperature were assessed as primary outcomes and albumin, prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), other hematological parameters, blood pressure, O2 saturation, ICU duration, and 28-mortality rate were assessed as secondary outcomes. RESULTS: Fifty-two participants completed the trial. CRP and ESR levels were not significantly different between CoQ10 and placebo groups at the end of the study (P = 0.550 and P = 0.306, respectively). No significant differences between groups were observed for TAC (P = 0.865), MDA (P = 0.692), and SOD activity (P = 0.633) as well. Administration of CoQ10 resulted in a significant increase in albumin levels compared to placebo (P = 0.031). There was no statistically significant difference between the two groups in other measured outcomes (P > 0.05). CONCLUSION: Results showed that in patients with burn injury, CoQ10 administration had no effect on inflammatory markers and oxidative stress, although serum albumin levels were improved after supplementation. Further studies with albumin as the primary outcome are needed to confirm this finding.

Therapeutic effects of saffron and its components on neurodegenerative diseases.

Due to an increase in the number of older people in recent years, neurodegenerative diseases as the most important age-related neurological disorders are considered as a great threat to human health. The treatment strategies for these disorders are symptomatic and there is no known definitive treatment; however, recently, several studies have investigated the effectiveness of some herbs and their components in limiting the progression and treatment of neurodegenerative disorders. In this study, we searched Medline (via PubMed), Scopus, Science Direct, and Google Scholar databases. The keywords used in the search were: saffron [title/abstract] or (saffron compound [title/abstract]) and (neurological disorders [title/abstract]), publication date range (2010-2023), and language (English). After applying inclusion and exclusion criteria, 30 articles remained. Of the 30 articles included in the study, six studies on the treatment of neurodegenerative disorders by saffron and its components were in the clinical trial phase, and 24 studies were in the preclinical phase. Saffron and its compounds can play an important role in inhibiting neuroinflammation and excitotoxic pathways, modulating autophagy and apoptosis, attenuating oxidative damage, and activating defensive antioxidant enzymes, resulting in neuroprotection against neurodegenerative diseases. Therefore, this study aimed to review the studies on the effects of saffron and its compounds on the treatment of neurodegenerative diseases.

Curcumin supplementation effect on liver enzymes in patients with nonalcoholic fatty liver disease: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials.

CONTEXT: Clinical evidence from investigations of the effects of curcumin on liver enzymes in patients with nonalcoholic fatty liver disease (NAFLD) have led to inconsistent results. OBJECTIVE: The aim of this systematic review and meta-analysis was to investigate the overall effects of curcumin and curcumin plus piperine supplementation on liver enzymes such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) in patients with NAFLD. DATA SOURCES: The Scopus, Web of Science, PubMed, and Cochrane Library databases were searched from inception through July 2023, using search terms representing NAFLD and liver enzymes. Articles were screened independently by 2 researchers based on PICOS inclusion criteria. DATA EXTRACTION: The following data were extracted: first author's name, study location, year of publication, mean age, study duration, study design, participants' sex, number of participants in each group, dose of curcumin supplementation, and ALT, ALP, and AST concentrations. Risk of bias was assessed using the Cochrane Collaboration's modified risk-of-bias tool. DATA ANALYSIS: Fixed- or random-effects meta-analysis was performed to estimate the effects of curcumin on liver enzymes, considering heterogeneity across studies. The I2 and Cochran's Q tests were used to assess heterogeneity between studies. RESULTS: Overall, 15 randomized controlled trials comprising 905 participants were eligible for this meta-analysis. Curcumin supplementation significantly reduced ALT (weighted mean difference [WMD], -4.10, 95%CI, -7.16 to -1.04) and AST (WMD, -3.27; 95%CI, -5.16 to -1.39), but not ALP (WMD, -0.49; 95%CI, -1.79 to 0.82). Curcumin plus piperine supplementation had no significant effect on ALT (WMD, -3.79; 95%CI, -13.30 to 5.72), and AST (WMD, -1.1; 95%CI, -3.32 to 1.09). CONCLUSIONS: Curcumin supplementation improved AST and ALT levels compared with the control group. However, better-designed randomized controlled trials with larger sample sizes and of higher quality are needed to assess the effects of curcumin on ALP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023448231.

Low plasma vitamin D is associated with increased 28-day mortality and worse clinical outcomes in critically ill patients.

BACKGROUND & OBJECTIVE: Patients in the intensive care unit have a high prevalence of vitamin D deficiency (VDD). In the present study, clinical outcomes in the ICU were analyzed with vitamin D status. MATERIALS AND METHODS: In this prospective, multicenter study, sampling was conducted on seven ICUs in three hospitals. Within the first 24 h of ICU admission, patient's serum vitamin D levels were measured, and their disease severity was monitored using the scores of acute physiologic assessment and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), and the modified Nutrition Risk in Critically ill (mNUTRIC) score. RESULTS: A total of 236 patients were enrolled in this study, of which 163 (69.1%) had lower vitamin D levels than 20 ng/ml upon ICU admission. The patients with VDD had higher APACHE II scores)P = 0.02), SOFA scores (P < 0.001), and mNUTRIC scores (P = 0.01). Patients with sufficient levels of vitamin D (> 30 ng/ml) had a shorter stay at ICU (P < 0.001). VDD was independently associated with 28-day mortality (OR: 4.83; 95% CI: 1.63-14.27; P = 0.004). CONCLUSION: The data showed that VDD was common among the critically ill and was related to a more severe course of illness and a higher mortality rate.

Synthetic Curcumin Analogs in the Treatment of Cancer: A Literature Review.

Treatment of cancer, one of the most fatal diseases in the present century, has become a topic of global concern. Unfavorable unintentional effects of chemotherapy and radiation treatments have been the main reasons for the research on the discovery of drugs with a broader spectrum of effectiveness and efficiency, with minimal side effects. Curcumin (diferuloylmethane) is a naturally occurring phenolic structure with anticancer properties through its inhibition of cell multiplication, metastasis, and prolongation of cell cycle suppression of apoptosis in various tumor cells. The primary restriction regarding the use of curcumin in cancer treatment is related to poor bioavailability and unfavorable pharmacokinetic profiles of curcumin due to its poor absorption rate, fast metabolism, and systemic elimination. A variety of ways have been proposed to overcome these limitations. With this background, the present study focuses on providing a comprehensive overview of the anticancer properties of curcumin derivatives and the synthesis of curcumin analogs with application to different types of cancers. The regulation of various target and signaling pathways is considered in various cancers, including breast, gastrointestinal, pancreatic, prostate, skin, and lung cancers. A review of the literature indicates that modifying the structure of curcumin through the substitution of the phenyl group and unsaturated carbon branch around the two main sites of oxygen can result in the improvement of physical and chemical properties, as well as the enhancement of physiological activities of the curcumin molecule and the anti-cancer activities of this polyphenol. Curcumin analogs demonstrate anticancer properties at multiple targets at different cell stages and by various signaling biochemical pathways. These include cytokines, transcription factors, growth factors, and modulation of genes involved in cellular proliferation and apoptosis in breast, gastrointestinal, skin, prostate, and lung cancers, thereby mitigating tumor progression.

The relation of dietary protein intake before and during the pregnancy with gestational diabetes mellitus (GDM): A GRADE-assessed systematic review and dose-response meta-analysis of epidemiologic studies.

BACKGROUND: Although previous studies investigated the relation of protein intake and gestational diabetes mellitus (GDM), their findings were controversial. Therefore, we aimed to summarize this association, through a comprehensive systematic review and dose-response meta-analysis. METHODS: Electronic databases including MEDLINE (PubMed), ISI Web of Science, Scopus and motor engineering of Google Scholar were systematically searched up to April 2023. Observational studies which investigated odds of GDM in relation to protein intake were included. RESULTS: A total of 31,005 participants with 3451 cases of GDM from 13 eligible investigations were included in the systematic review and meta-analysis. Comparing the highest and lowest intakes of total, animal, and plant proteins revealed the summary RRs of 1.82 (95% CI: 1.42, 2.33), 1.79 (95% CI: 1.50, 2.14), and 0.98 (95% CI: 0.81, 1.20), respectively, indicating a significant positive association between total and animal protein intake and GDM. In the dose-response analyses, each 5% increment in energy intake from total protein during pregnancy was related to 20% increased odds of GDM (RR = 1.20; 95% CI: 1.09, 1.33). In the non-linear dose-response analyses, we found a non-linear association for animal protein intake during pregnancy (P for non-linearity <0.001); so that, a risk increase was seen from zero to 10% of energy intake from animal proteins, however, a risk reduction was seen after 10% of energy intake. However, there was not any significant non-linear trend between plant protein intake during pregnancy and risk of GDM. Based on the GRADE assessment, the quality of evidence for total, animal and plant protein was rated as "moderate", "moderate" and "very low", respectively. CONCLUSION: We found a significant positive association between total protein intake and GDM; however, the associations of animal and plant protein intake with GDM were dose-dependent.

Effects of therapeutic lifestyle change diets on blood lipids, lipoproteins, glycemic parameters, and blood pressure: a systematic review and meta-analysis of clinical trials.

CONTEXT: Cardiovascular disease is the leading cause of death worldwide. Low-calorie, low-fat therapeutic diets (TDs) developed by the US National Cholesterol Education Program, ie, the Step I and II diets and the therapeutic lifestyle changes diet, are approximately similar and are the initial therapeutic interventional approaches for lifestyle modification. OBJECTIVE: This systematic review with meta-analysis was undertaken to evaluate the effects of TDs diet on blood lipids, apolipoprotein A-1, apolipoprotein B, blood pressure, fasting blood glucose, and insulin. DATA SOURCES: A comprehensive search of the PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar databases until October 2022 was performed to identify clinical trials investigating the effects of TDs on the aforementioned parameters. DATA EXTRACTION: One investigator screened the records and extracted data, and another reviewed the extracted data. DATA ANALYSIS: A total of 910 records were retrieved. After records were screened for eligibility, 34 clinical trials met the inclusion criteria. The pooled analysis from the random-effects model revealed a significant reduction in total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-1, and apolipoprotein B in the TD intervention group vs the control group. The overall effects of TDs on fasting blood glucose, insulin, and blood pressure were not significant, but the results of subgroup analysis revealed a significant reduction in fasting blood glucose with the Step II diet and an intervention duration of more than 24 weeks. For blood pressure, the Step I diet and an intervention duration of more than 24 weeks resulted in significant reduction. There was no evidence of publication bias, but strong heterogeneity was observed. CONCLUSION: Therapeutic diets have promising effects on lipid profile parameters, glycemic indexes, and blood pressure, which can promote cardiovascular health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021259355.

The effects of oral trehalose on glycaemia, inflammation, and quality of life in patients with type 2 diabetes: a pilot randomized controlled trial.

Introduction: Trehalose is a naturally occurring disaccharide of 2 glucose molecules, which has been suggested as a potential therapeutic agent to reduce blood glucose and ameliorate diabetes-related complications in type 2 diabetes (T2D). This study aimed to determine the efficacy of medium-term trehalose treatment in patients with T2D. Material and methods: A double-blind, randomized, placebo-controlled trial in 40 patients with T2D was undertaken; 20 ingested trehalose 3.3 g/day and 20 placebo (sucrose), for 3 months. Parameters of glycaemic indices, high-sensitivity C-reactive protein (CRP), mood status, and quality of life were measured. Results: CRP was significantly lower with trehalose treatment (-0.62 ±0.3 mg/l, p = 0.02); however, no differences in glycaemic indices of fasting blood glucose (FBG) (-7.1 ±10.7 mg/dl, p = 0.15), glycated hemoglobin (HbA1c) (-0.1 ±0.4%, p = 0.73), insulin (0.73 ±0.8 µU/ml, p = 0.39), or insulin resistance (HOMA-IR) (0.19 ±0.33, p = 0.56) were seen between groups after 12 weeks. Depression and stress scores were lower with trehalose compared to the placebo group (p = 0.02 and p = 0.05, respectively), whilst the quality-of-life score was higher with trehalose compared to placebo (p = 0.03) at the end of study. Between-group differences in these indices did not reach statistical significance (-2.36 ±1.20, -2.21 ±1.39 and 3.00 ±1.76 for depression, stress, and quality-of-life score, respectively) (p > 0.05). The pro-oxidant antioxidant balance (PAB) did not differ between groups (-4.6 ±12.8, p = 0.72). Conclusions: 12 weeks of treatment with 3.3 g/day of oral trehalose significantly improves CRP as a marker of inflammation, with potential favourable effects on quality of life, depression, and stress levels, but overall glycaemic control and pro-oxidant-antioxidant balance were unaltered during this time frame.

Animal protein intake is directly associated with serum level of pentraxin 3 in hemodialysis patients.

Inflammation plays an important role in Cardiovascular disease (CVD) pathogenesis as the main cause of mortality in hemodialysis (HD) patients. Despite the relevance of nutrition and dietary intakes for inflammation status, the role of dietary protein sources remains unclear. The aim of this study was to evaluate the association between the different types of dietary protein and pentraxin 3 (PTX3) levels in HD patients. In this multi-center cross-sectional study, 227 adult patients undergoing HD for a minimum 90 days were recruited. A validated 168-item food frequency questionnaire was used to assess dietary intakes. Also, 5 ml blood samples were collected from each patient to measure the concentration of serum PTX3. Overall, 227 patients, including 63 women and 164 men, with a mean age of 58 years, participated in this study. There was a greater intake of animal protein per kilogram dry weight among patients with higher levels of PTX3 (0.46 vs. 0.54 g/kg; P = 0.035). In contrast, consumption of total protein and plant protein per kilogram dry weight was not different across PTX3 levels. Moreover, the chance of increased PTX3 concentration was directly associated with a one-unit increase in animal protein intake per kilogram dry weight, after adjusting for confounders. We did not observe any association between one-unit increases in plant protein intake per kilogram dry weight and chance of increased PTX3. In conclusion, animal protein intake was directly associated with circulating PTX3.