Predictive model for vitamin C levels in hyperinsulinemic individuals based on age, sex, waist circumference, low-density lipoprotein, and immune-associated serum proteins.

Vitamin C (ascorbic acid) is an important water-soluble antioxidant associated with decreased oxidative stress in type 2 diabetes (T2D) patients. A previous targeted plasma proteomic study has indicated that ascorbic acid is associated with markers of the immune system in healthy subjects. However, the association between the levels of ascorbic acid and blood biomarkers in subjects at risk of developing T2D is still unknown. Serum ascorbic acid was measured by ultra-performance liquid chromatography and serum proteins were quantified by untargeted liquid-chromatography mass spectrometry in 25 hyperinsulinemia subjects that were randomly assigned a high dairy intake diet or an adequate dairy intake diet for 6 weeks, then crossed-over after a 6-week washout period. Spearman correlation followed by gene ontology analyses were performed to identify biological pathways associated with ascorbic acid. Finally, machine learning analysis was performed to obtain a specific serum protein signature that could predict ascorbic acid levels. After adjustments for waist circumference, LDL, HDL, fasting insulin, fasting blood glucose, age, gender, and dairy intake; serum ascorbic acid correlated positively with different aspects of the immune system. Machine learning analysis indicated that a signature composed of 21 features that included 17 proteins (mainly from the immune system), age, sex, waist circumference, and LDL could predict serum ascorbic acid levels in hyperinsulinemia subjects. In conclusion, the result reveals a correlation as well as modulation between serum ascorbic acid levels and proteins that play vital roles in regulating different aspects of the immune response in individuals at risk of T2D. The development of a predictive signature for ascorbic acid will further help the assessment of ascorbic acid status in clinical settings.

Dairy Intake Modifies the Level of the Bile Acid Precursor and Its Correlation with Serum Proteins Associated with Cholesterol Clearance in Subjects with Hyperinsulinemia.

Bile acids regulate glucose homeostasis and lipid metabolism. Further, the levels of bile acids can be influenced by the intake of dairy products. Although the serum proteome can provide information on the biological pathways associated with different metabolites, it is unknown whether the intake of dairy modifies such associations between bile acids and the proteome. The objectives of this study were to examine plasma bile acid profiles, find the correlations between bile acids and lipid as well as glycemic markers, and to uncover the correlation between bile acids and proteins after high dairy (HD) and adequate dairy (AD) intake among 25 overweight individuals with hyperinsulinemia. In this randomized crossover-trial study, hyperinsulinemia adults were randomized to both HD (≥4 servings/day) and AD (≤2 servings/day) for 6 weeks. Measurements and analyses were performed on before- as well as after- AD and HD conditions. The results indicated that plasma 7α-hydroxy-4-cholesten-3-one (7AC4) increased after HD in comparison with before HD intake (p = 0.03). After adjusting for BMI, age, and sex, 7AC4 positively correlated with triglyceride levels in the pre-AD (r = 0.44; p = 0.03) and post-HD (r = 0.42; p = 0.04). Further, 7AC4 correlated positively with proteins associated with high-density lipoprotein particle remodeling pathway and reverse cholesterol transport only after HD consumption. Thus, the consumption of higher dairy intake modifies the association between 7AC4-a biomarker for bile acid synthesis-and serum proteins involved in cholesterol clearance. Overall, higher dairy consumption may have a positive effect on cholesterol metabolism in subjects at risk of type 2 diabetes.

The effect of probiotics on oxidized LDL levels: A systematic review and meta-analysis of clinical trials.

BACKGROUND: It has been widely reported that the use of probiotics has beneficial effects on the prevention and treatment of a wide range of human diseases. Previous clinical trials have investigated the effect of probiotics on oxLDL, but the results are controversial. OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis of clinical trials to assess the effect of probiotic consumption on oxLDL levels. METHOD: A comprehensive search was conducted in PubMed, ISI Web of Science, and Scopus using the appropriate search strategy. After the screening, seven studies comparing the effects of probiotic consumption with the control were included in the analysis. A random-effects analysis was used to estimate the overall effect size. RESULTS: Probiotic supplementation significantly reduced oxLDL (Hedge's: -1.18; 95% CI:-1.85, -0.52) compared to the control group. Subgroup analysis showed that reduction was greater in the unhealthy group compared to healthy subjects (-2.05 vs. -0.84). The results also showed that probiotic supplementation reduced TC by -14.77 mg/dl (95% CI: -24.46, -5.08), LDL-C by -10.03 mg/dl (95% CI: -16.05, -4.001), LDL-C/HDL-C ratio by -0.37 (95% CI: -0.66, 0.07), and TG by -14.86 mg/dl (95% CI: -23.45, -6.28) but the effects on HDL-C and glucose were not significant. CONCLUSION: In this study, probiotic supplementation was found to improve oxLDL concentrations and have favorable effects on lipid profiles, but no significant positive effect on HDL-C and glucose was reported. However, the findings should be interpreted with caution due to the low number of included studies.

The relationship between a plant-based diet and mental health: Evidence from a cross-sectional multicentric community trial (LIPOKAP study).

BACKGROUND: Dietary patterns emphasizing plant foods might be neuroprotective and exert health benefits on mental health. However, there is a paucity of evidence on the association between a plant-based dietary index and mental health measures. OBJECTIVE: This study sought to examine the association between plant-based dietary indices, depression and anxiety in a large multicentric sample of Iranian adults. METHODS: This cross-sectional study was performed in a sample of 2,033 participants. A validated food frequency questionnaire was used to evaluate dietary intakes of participants. Three versions of PDI including an overall PDI, a healthy PDI (hPDI), and an unhealthy PDI (uPDI) were created. The presence of anxiety and depression was examined via a validated Iranian version of the Hospital Anxiety and Depression Scale (HADS). RESULTS: PDI and hPDI were not associated to depression and anxiety after adjustment for potential covariates (age, sex, energy, marital status, physical activity level and smoking). However, in the crude model, the highest consumption of uPDI approximately doubled the risk of depression (OR= 2.07, 95% CI: 1.49, 2.87; P<0.0001) and increased the risk of anxiety by almost 50% (OR= 1.56, 95% CI: 1.14, 2.14; P= 0.001). Adjustment for potential confounders just slightly changed the associations (OR for depression in the fourth quartile= 1.96; 95% CI: 1.34, 2.85, and OR for anxiety in the fourth quartile= 1.53; 95% CI: 1.07, 2.19). CONCLUSIONS: An unhealthy plant-based dietary index is associated with a higher risk of depression and anxiety, while plant-based dietary index and healthy plant-based dietary index were not associated to depression and anxiety.

The beneficial therapeutic effects of plant-derived natural products for the treatment of sarcopenia.

Sarcopenia is an age-related muscle disorder typically associated with a poor quality of life. Its definition has evolved over time, and several underlying causes of sarcopenia in the elderly have been proposed. However, the exact mechanisms involved in sarcopenia, as well as effective treatments for this condition, are not fully understood. The purpose of this article was to conduct a comprehensive review of previous evidence regarding the definition, diagnosis, risk factors, and efficacy of plant-derived natural products for sarcopenia. The methodological approach for the current narrative review was performed using PubMed, Scopus, and Web of Science databases, as well as Google Scholar (up to March 2021) in order to satisfy our objectives. The substantial beneficial effects along with the safety of some plant-derived natural products including curcumin, resveratrol, catechin, soy protein, and ginseng on sarcopenia are reported in this review. Based on clinical studies, nutraceuticals and functional foods may have beneficial effects on physical performance, including handgrip and knee-extension strength, weight-lifting capacity, time or distance travelled before feeling fatigued, mitochondrial function, muscle fatigue, mean muscle fibre area, and total number of myonuclei. In preclinical studies, supplementation with herbs and natural bioactive compounds resulted in beneficial effects including increased plantaris mass, skeletal muscle mass and strength production, increased expression of anabolic factors myogenin, Myf5 and MyoD, enhanced mitochondrial capacity, and inhibition of muscle atrophy and sarcopenia. We found that several risk factors such as nutritional status, physical inactivity, inflammation, oxidative stress, endocrine system dysfunction, insulin resistance, history of chronic disease, mental health, and genetic factors are linked or associated with sarcopenia. The substantial beneficial effects of some nutraceuticals and functional foods on sarcopenia, including curcumin, resveratrol, catechin, soy protein, and ginseng, without any significant side effects, are reported in this review. Plant-derived natural products might have a beneficial effect on various components of sarcopenia. Nevertheless, due to limited human trials, the clinical benefits of plant-derived natural products remain inconclusive. It is suggested that comprehensive longitudinal clinical studies to better understand risk factors over time, as well as identifying a treatment strategy for sarcopenia that is based on its pathophysiology, be undertaken in future investigations.

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 phytochemicals and herbal bio-active compounds on tumour necrosis factor-α in overweight and obese individuals: a clinical review.

Obesity is abnormal fat accumulation in the body which acts as a risk factor for various cardiometabolic states. Adipose tissue in excess can release inflammatory factors, including TNF-α and IL-6, and suppress adiponectin production. TNF-α increases the levels of IL-6 and acute phase reactants such as C-reactive protein. Inflammation has a crucial role in developing and progressing various cardiometabolic diseases and a wide range of obesity-related complications. It has been shown that TNF-α has a significant role in the development of insulin resistance. Recently, a growing body of evidence has focused on herbal medicine, phytochemicals and natural bioactive compounds as inexpensive, relatively easy accessible agents with low adverse effects to reduce inflammatory markers such as TNF-α and simultaneously decrease insulin resistance, glucose intolerance, and dyslipidemia in obesity. The main focus of the current review is to summarize the results of the studies, which assessed the effects of phytochemicals and herbal bio-active compounds on serum TNF-α in subjects with overweight or obesity. This review suggests that herbal medicine have favorable effects on the reduction of TNF-α concentration; however, the results were not uniform for different products. Among the reviewed plants, ginger, ginseng, resveratrol, and flaxseed had more promising effects.

The effect of the Dietary Approaches to Stop Hypertension (DASH) diet on body composition, complete blood count, prothrombin time, inflammation and liver function in haemophilic adolescents.

There is no dietary strategy that has yet been specifically advocated for haemophilia. Therefore, we sought to assess the effect of the Dietary Approaches to Stop Hypertension (DASH) diet in adolescents with haemophilia. In this parallel trial, forty male adolescents with haemophilia were dichotomised into the DASH group or control group for 10 weeks. The serum high sensitivity C-reactive protein, IL-6, complete blood count (CBC), serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, partial thromboplastin time (PTT), waist circumference (WC), percentage of body fat, fat-free mass and liver steatosis were measured at the beginning and end of the study. Serum vitamin C was measured as a biomarker of compliance with the DASH diet. The DASH diet was designed to include high amounts of whole grains, fruits, vegetables and low-fat dairy products, as well as low amounts of saturated fats, cholesterol, refined grains, sweets and red meat. Serum vitamin C in the DASH group was significantly increased compared with the control (P = 0·001). There was a significant reduction in WC (P = 0·005), fat mass (P = 0·006), hepatic fibrosis (P = 0·02) and PTT (P = 0·008) in the DASH group, compared with the control. However, there were no significant differences regarding other selected outcomes between groups. Patients in the DASH group had significantly greater increase in the levels of erythrocyte, Hb and haematocrit, as compared with the control. Adherence to the DASH diet in children with haemophilia yielded significant beneficial effects on body composition, CBC, inflammation and liver function.

Effect of Curcumin on Glycemic Control in Patients with Type 2 Diabetes: A Systematic Review of Randomized Clinical Trials.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition, which carries considerable morbidity and mortality. There is growing evidence that curcumin could modulate glucose homeostasis and improve vascular risk in patients with T2DM. The aim of this systematic review was to study the effect of curcumin on glycemic indices in patients with diabetes. A comprehensive search was conducted in PubMed, Scopus, Embase, and Google Scholar up to March 5, 2020, to identify randomized control trials investigating the effect of curcumin supplementation on glycemic indices including fasting blood glucose (FBS), hemoglobin A1c (HbA1C), and the homeostatic model assessment for insulin resistance (HOMA-IR). Eleven articles comprising 1131 individuals with T2DM were included in the study. Treatment with curcumin significantly reduced the level of FBS and HbA1c in 8 and 7 studies, respectively. HOMA-IR was evaluated in five studies, and this was reduced significantly by curcumin supplementation in three of those studies. Patients who took curcumin supplementation over longer periods (≥12 weeks) showed a significant reduction in glycemic indices. The current systematic review showed that curcumin can improve glycemic control in patients with T2DM. However, further studies are required to determine the optimum conditions for these effects of curcumin, particularly regarding readouts of insulin resistance.

Medicinal Plants and Phytochemicals Regulating Insulin Resistance and Glucose Homeostasis in Type 2 Diabetic Patients: A Clinical Review.

Diabetes is a major health problem affecting more than four hundred million adults worldwide. The transition from normal glucose tolerance to type 2 diabetes (T2D) is preceded by increased Insulin resistance (IR), an independent predictor of the development of T2D in high risk (e.g. obese populations, pre-diabetes) individuals. Insulin deficiency resulting from increased IR results in progressive glucose homeostasis dysfunction. Data has shown that IR is affected by many different factors such as genetics, age, exercise, dietary nutrients, obesity, and body fat distribution. One of the most important factors is diet, which plays an essential role in addressing T2D and metabolic syndrome. Nutraceuticals and medicinal plants have been shown to have efficacy in preventing chronic diseases like cancer, non-alcoholic fatty liver disease (NAFLD), cardiovascular disease, diabetes mellitus and metabolic syndrome, likely through the anti-inflammatory properties found in nutraceuticals. However, the effect of these compounds, including traditional plant medicines, herbal formulations or their extracts on IR have not been systematically investigated. The objective of this review was to assess the reported effects of medicinal plants and bioactive natural compounds on IR. The findings confirm that most of the herbal bioactive compounds including resveratrol, garlic, curcumin, cinnamon, ginger, nuts, berberine, anthocyanin, soybean, flaxseed, vegetable oils, and soluble fibers have benefit in their efficacy for decreasing IR, fasting blood sugar (FBS), fasting insulin and HbA1c.

Salt intake and its sources in children, adolescents and adults in the Islamic Republic of Iran.

BACKGROUND: There is little evidence about salt intake and its food sources in the Iranian population, especially in children and adolescents. AIMS: To investigate salt intake and dietary sources in Isfahan, Islamic Republic of Iran. METHODS: This was a cross-sectional survey conducted in 2014-2015. We randomly selected 1384 adults (50.3% female, 49.7% male) aged > 18 years [mean 37.9 (10.6) years], and 786 children and adolescents (50.9% male, 49.1% female) aged 6-18 years [mean 12.5 (3.4) years]. All participants underwent a dietary assessment for salt intake, using a validated food frequency questionnaire. RESULTS: The total salt intake was 10.9 (3.4) g/day in adults and 10.3 (2.9) g/day in children and adolescents. Added salt was the primary source of salt intake, followed by bread and cheese in both groups. Salt intake was related significantly to being younger, male, a smoker, less educated and physically active in the adult group. In children and adolescents, it was significantly associated with increasing age, male sex, low physical activity and parents' education level (all P < 0.05). CONCLUSIONS: Salt intake in Isfahan was more than twice that recommended by the World Health Organization. The main source of sodium was added salt, followed bread and cheese. Future national studies are warranted to assess the dietary salt intake and its main sources in different provinces in the Islamic Republic of Iran.

Effects of the dietary approach to stop hypertension (DASH) diet on blood pressure, blood glucose, and lipid profile in adolescents with hemophilia: A randomized clinical trial.

Children with hemophilia are an enhanced risk of modifiable cardiovascular and metabolic abnormalities. There is currently no nutritional guideline to prevent or manage cardiometabolic risk factors in these patients. Therefore, the present study sought to investigate the effect of the Dietary Approaches to Stop Hypertension (DASH) diet on cardiovascular and metabolic risk factors among children with hemophilia. In this parallel randomized clinical trial, 40 children (all male) with hemophilia were randomly allocated to the DASH group (n = 20) or control group (n = 20) for 10 weeks. The intervention group received the DASH diet (50%-55% of energy from carbohydrate, 27%-30% of energy from fat and 16%-18% energy from protein), and the control group received nutritional recommendations based on healthy eating practices. Systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood sugar (FBS), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were measured at the beginning and end of the study. Serum vitamin C was measured as a biomarker of compliance with the DASH diet. Study was registered at IRCT.ir (IRCT20130903014551N6). A significant increase in serum vitamin C in the DASH diet group was observed compared to the control group (p = .001), indicating good compliance with the DASH diet. There was a significant reduction in SBP (-0.48 mmHg), DBP (-0.48 mmHg), FBS (-5.86 mg/dl), TC (-16.07 mg/dl), TG (-17.21 mg/dl), and LDL-C (-9.79 mg/dl), and a significant increase in HDL-C (3.39 mg/dl), in the DASH diet group compared with the control group. Adherence to the DASH diet in children with hemophilia yielded beneficial effects in blood pressure, lipid profiles, and FBS.

Effect of levetiracetam drug on antioxidant and liver enzymes in epileptic patients: case-control study.

BACKGROUND: There is a limited amount of data regarding levetiracetam (LEV), an antiepileptic drug. OBJECTIVE: This study was conducted to assess the effect of LEV on antioxidant status and liver enzymes. METHODS: In this case-control study, 33 epileptic patients under treatment with LEV for at least 6 months were compared with 35 healthy subjects. We measured serum total antioxidant capacity (TAC), salivary superoxide dismutase (SOD), alanine aminoteransferase (ALT), and aspartate aminoteransferase (AST) levels in both groups. Dietary intakes were collected using a Food Frequency Questionnaire (FFQ). RESULT: The level of TAC in the healthy subjects was significantly higher than it was in the patients (P=0.02), but the mean of ALT (P=0.02) and AST (P=0.03) was significantly higher in the patients in comparison with the controls. Mean salivary SOD showed no difference between the two groups. In the patients, the duration of drug use was inversely correlated with serum TAC (p=0.04) and had a direct correlation with ALT (p=0.01) and AST (p=0.03.). CONCLUSION: The results of our study indicated that LEV increased liver enzymes Also, treatment with this drug did not improve oxidative stress, but this could be due to the different in the dietary antioxidant intake. Routine screening of the liver and antioxidant enzymes in patients with chronic use of LEV is recommended.

Medicinal plants and bioactive natural compounds as inhibitors of HMG-CoA reductase: A literature review.

Cardiovascular diseases (CVDs) are one of the most important causes for mortality worldwide. Elevated levels of total cholesterol, and particularly LDL-cholesterol (LDL-C) are the main risk factor for acute myocardial infarction (AMI) and ischemic heart disease. The risk of CVDs could be reduced by decreasing the elevated cholesterol levels. ß-hydroxy ß-methylglutaryl-CoA reductase (HMGCoAR) is the primary and rate-limiting enzyme in the cholesterol biosynthesis pathway. Recently, the crucial role of nutraceuticals in maintaining normal physiological function was established. Nutraceuticals play an important role in preventing several non-communicable diseases such as obesity, CVDs, cancer, diabetes, and reducing hyperlipidemia. Although the effect of nutraceuticals and herbal medicine on CVDs and dyslipidemia was previously investigated thoroughly, the effect of these natural products on HMGCoAR as one of the important enzymes involved in CVDs etiopathogenesis has not yet been investigated. Therefore, the major aim of this paper was to review the effects of nutraceuticals and medicinal plants on HMGCoAR. Results indicate that different types of natural foods, isolated nutrients, herbal products, and dietary supplements as nutraceuticals decrease the expression and activity of HMGCoAR. This review shows that medicinal plants and nutraceuticals could be used to decrease HMGCoAR activity as accessible and convenient and economical natural compounds to prevent dyslipidemia and CVDs.

Vitamin B12 and Folate Status in Patients with Epilepsy Under Levetiracetam Monotherapy.

BACKGROUND: Antiepileptic drugs (AEDs) may lead to an increase in the plasma concentration of homocysteine. There is limited information, especially from Iran, regarding the risk in patients who are treated with levetiracetam as a new type of AED. The aim of the present study was to investigate the effect of levetiracetam on plasma homocysteine, vitamin B12, and folate levels in adult patients with epilepsy. METHODS: We conducted a case-control study and enrolled adult patients with epilepsy who had received monotherapy with levetiracetam for at least 6 months at some time prior to the study. homocysteine serum, vitamin B12, and folate were measured, and folate and vitamin B12 intake was determined by the food frequency questionnaire (FFQ). RESULTS: Thirty-three patients on levetiracetam and 35 control subjects aged between 18 and 60 years were enrolled. No statistically significant differences in the means of the serum markers of vitamin B12, FA, and homocysteine levels were found between the two groups. In the first model, i.e., the crude model, no significant differences were observed in the serum concentrations of homocysteine, vitamin B12, and folate. In the second model, education was considered, and body mass index and folate intake was controlled with no significant difference being observed in the mean homocysteine serum level. CONCLUSIONS: Treatment with levetiracetam in patients with epilepsy has no effect on the serum levels concentrations of homocysteine, vitamin B12, and folate. This medication is suggested for patients who use AEDs on a long-term basis and at high dosages.

Do probiotics, prebiotics and synbiotics affect adiponectin and leptin in adults? A systematic review and meta-analysis of clinical trials.

BACKGROUND & AIMS: Human studies have reported controversial findings regarding the health promoting effects of probiotic, prebiotic and synbiotic on adiponectin and leptin levels. This systematic review and meta-analysis was conducted to understand the effect of probiotics, prebiotics or synbiotics on adiponectin and leptin levels in adults. METHODS: Electronic searches were performed in PubMed, Scopus, Web of Science, Cochrane Library and Google scholar up to February 11, 2018 without any restriction. Controlled clinical trials, in any age of adults, which reported the effect of probiotic, prebiotic and synbiotic on serum level of adiponectin and leptin were included. As leptin and adiponectin were reported in different units across the studies, Hedges's adjusted g was used to calculate effect size. A random-effects model was used to pool calculated effect sizes. RESULTS: Of 12 eligible studies, 10 publications focused on probiotics, and only 3 studies reported the effect of prebiotics (n = 2) or synbiotics (n = 1) on leptin and adiponectin. There were no significant changes in adiponectin (Hedges' g = -0.04; 95% CI: -0.27, 0.19) and leptin (Hedges' g = -0.30; 95% CI: -0.86, 0.26) in probiotic group compared with controls. Subgroup analyses ranged in heterogeneity from 0% to 93%, but no subgroup showed an effect of probiotics on adiponectin or leptin. CONCLUSION: There were limited studies regarding the effect of prebiotic and synbiotic on adiponectin and leptin. Although previous studies reported several health promoting effects of probiotics, we could not find any pooled effect on adiponectin and leptin.