A network meta-analysis on the comparative effect of nutraceuticals on lipid profile in adults.

It is estimated that 2.6 million deaths worldwide can be attributed to hypercholesterolemia. The main reason for non-adherence to statin therapy are the statin-associated muscle symptoms (including nocebo/drucebo effect). In this case, apart from ezetimibe, nutraceuticals are prescribed. We aimed to assess the comparative efficacy of different nutraceuticals in terms of lowering low density lipoprotein cholesterol (LDL-C) and improving lipid profile. Electronic and hand searches were performed until February 2021. The inclusion criteria were the following: (1) randomized trial with any of the reportedly LDL-C lowering nutraceutical: artichoke, berberine, bergamot, garlic, green tea extract, plant sterols/stanols, policosanols, red yeast rice (RYR), silymarin or spirulina. (2) outcome either LDL-C (primary outcome), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) or serum triglycerides (TG). Random effects network meta-analysis (NMA) was performed to rank the effect of each intervention using frequentist approach. Finally, a total of 131 trials enrolling 13,062 participants were included. All analysed nutraceuticals except for policosanols were more effective in lowering LDL-C (-1.21 [-46.8 mg/dL] to -0.17 [-6.6 mg/dL] mmol/l reduction) and TC (-1.75 [-67.7 mg/dL] to -0.18 [7 mg/dL] mmol/l reduction) than placebo/no intervention. The most effective approaches in terms of LDL-C- and TC-lowering were bergamot and RYR (-1.21 [-46.8 mg/dl] and -0.94 [-36.4 mg/dl] mmol/l) reduction respectively. In conclusion, bergamot and RYR appear to be the most effective nutraceuticals in terms of LDL-C and TC reduction. Evidence for bergamot effect was based on relatively small study group and may require further investigations. Policosanols have no effect on the lipid profile.

Comparative effect of nutraceuticals on lipid profile: a protocol for systematic review and network meta-analysis.

INTRODUCTION: According to the common definition, nutraceuticals are components found in food that can act as therapeutic substances. Recently, the International Lipid Expert Panel published two position papers covering the topic of lipid-lowering nutraceuticals and their potential use as a complementary treatment in addition to statins or as an alternative treatment in statin-intolerant patients. The aim of this study was to compare the effect of different nutraceuticals on lipid profiles in a systematic review with pairwise and network meta-analyses. METHODS AND ANALYSIS: Three databases, including PubMed, Embase and the Cochrane Central Register of Controlled Trials, will be searched without time or publication language restrictions. The estimated end date for the searches will be 29 March 2020. Each stage of the review, including the study section, data extraction, and risk of bias and quality of evidence assessments, will be performed in duplicate. Randomised controlled trials meeting the following criteria will be eligible for inclusion: (1) participants aged ≥18 years, (2) intervention with a selected nutraceutical (artichoke, berberine, bergamot, soluble fibres, green tea, garlic, lupin, plant sterols and stanols, red yeast rice, soybean, spirulina or a combination of the aforementioned nutraceuticals), (3) administration of the treatment in the form of capsules, pills, powders, solutions, tablets or enriched food items, (4) comparison with another nutraceutical or placebo, (5) intervention period ≥3 weeks and (6) lipid profile (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglycerides) as an outcome. Random-effect pairwise and network meta-analyses will be used to summarise the relative effect of each nutraceutical in comparison to the effect of every other nutraceutical. Subgroup analyses will be stratified by age, sex, ethnicity, sample size, length of trial follow-up, baseline cholesterol level and presence of other comorbidities. ETHICS AND DISSEMINATION: This review will summarise findings from primary studies, and therefore no ethics approval is required. The results will be presented at conferences as well as published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019132877.

Total antioxidant status reduction conditioned by a serum selenium concentration decrease as a mechanism of the ultrasonographically measured brachial artery dilatation impairment in patients with arterial hypertension.

The objective of the study was to determine the relationship between serum concentrations of selenium (SeS) and zinc (ZnS), total antioxidant status (TAS) and endothelial function assessed by ultrasonographic method of dilatation of the brachial artery in 141 hypertensive patients. Patients with SeS < median were characterized by a statistically significantly lower flow-mediated dilation (FMD) than patients with SeS ≥ median. Patients with TAS < median were characterized by a significantly lower FMD than patients with TAS ≥ median. Older age, higher BMI, male gender, higher blood total cholesterol, ischemic heart disease, smoking and lower SeS constitute independent predictors of inferior endothelial function, expressed in lower FMD values. Smoking is an independent predictor of lower TAS, and the use of ß-blockers and higher serum selenium levels are independent predictors of higher TAS. In summary, a decrease in TAS should be considered as a mechanism of inferior endothelial function in hypertensive patients conditioned by a decrease in SeS.

Alleviating Effect of α-Lipoic Acid and Magnesium on Cadmium-Induced Inflammatory Processes, Oxidative Stress and Bone Metabolism Disorders in Wistar Rats.

Cadmium exposure contributes to internal organ dysfunction and the development of chronic diseases. The aim of the study was to assess the alleviating effect of α-lipoic acid and/or magnesium on cadmium-induced oxidative stress and disorders in bone metabolism, kidney and liver function, and hematological and biochemical parameters changes. Male rats were exposed to cadmium (30 mg Cd/kg of feed) for three months. Some animals exposed to Cd were supplemented with magnesium (150 mg Mg/kg of feed) and/or with α-lipoic acid (100 mg/kg body weight, four times a week). Cd intake inhibited body weight gain and lowered hemoglobin concentration, whereas it increased the activities of liver enzymes, as well as the level of oxidative stress, CTX-1 (C-terminal telopeptide of type I collagen, bone resorption marker), and CRP (C-reactive protein, marker of inflammation); it decreased vitamin D3, GSH (reduced glutathione), and the serum urea nitrogen/creatinine index. Mg and/or α-lipoic acid supplementation increased the antioxidant potential, and partially normalized the studied biochemical parameters. The obtained results show that both magnesium and α-lipoic acid decrease oxidative stress and the level of inflammatory marker, as well as normalize bone metabolism and liver and kidney function. Combined intake of α-lipoic acid and magnesium results in reinforcement of the protective effect; especially, it increases antioxidant defense.

Blood Selenium Concentration and Blood Cystatin C Concentration in a Randomly Selected Population of Healthy Children Environmentally Exposed to Lead and Cadmium.

This study aimed at evaluation of a relationship between blood selenium concentration (Se-B) and blood cystatin C concentration (CST) in a randomly selected population of healthy children, environmentally exposed to lead and cadmium. The studies were conducted on 172 randomly selected children (7.98 ± 0.97 years). Among participants, the subgroups were distinguished, manifesting marginally low blood selenium concentration (Se-B 40-59 µg/l), suboptimal blood selenium concentration (Se-B: 60-79 µg/l) or optimal blood selenium concentration (Se-B ≥ 80 µg/l). At the subsequent stage, analogous subgroups of participants were selected separately in groups of children with BMI below median value (BMI <16.48 kg/m2) and in children with BMI ≥ median value (BMI ≥16.48 kg/m2). In all participants, values of Se-B and CST were estimated. In the entire group of examined children no significant differences in mean CST values were detected between groups distinguished on the base of normative Se-B values. Among children with BMI below 16.48 kg/m2, children with marginally low Se-B manifested significantly higher mean CST values, as compared to children with optimum Se-B (0.95 ± 0.07 vs. 0.82 ± 0.15 mg/l, p < 0.05). In summary, in a randomly selected population of healthy children no relationships could be detected between blood selenium concentration and blood cystatin C concentration. On the other hand, in children with low body mass index, a negative non-linear relationship was present between blood selenium concentration and blood cystatin C concentration.

Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers.

N-Acetylcysteine (NAC) could be included in protocols designed for the treatment of lead toxicity. Therefore, in this study, we decided to investigate the influence of NAC administration on homocysteine (Hcy) levels, oxidative damage to proteins, and the levels of iron (Fe), transferrin (TRF), and haptoglobin (HPG) in lead (Pb)-exposed workers. The examined population (n = 171) was composed of male employees who worked with Pb. They were randomized into four groups. Workers who were not administered any antioxidants, drugs, vitamins, or dietary supplements were classified as the reference group (n = 49). The remaining three groups consisted of workers who were treated orally with NAC at three different doses (1 × 200, 2 × 200, or 2 × 400 mg) for 12 weeks. After the treatment, blood Pb levels significantly decreased in the groups receiving NAC compared with the reference group. The protein concentration was not affected by NAC administration. In contrast, Hcy levels significantly decreased or showed a strong tendency toward lower values depending on the NAC dose. Levels of the protein carbonyl groups were significantly decreased in all of the groups receiving NAC. Conversely, glutamate dehydrogenase activity was significantly elevated in all of the groups receiving NAC, while the level of protein thiol groups was significantly elevated only in the group receiving 200 mg of NAC. Treatment with NAC did not significantly affect Fe and TRF levels, whereas HPG levels showed a tendency toward lower values. Treatment with NAC normalized the level of Hcy and decreased oxidative stress as measured by the protein carbonyl content; this effect occurred in a dose-dependent manner. Moreover, small doses of NAC elevated the levels of protein thiol groups. Therefore, NAC could be introduced as an alternative therapy for chronic Pb toxicity in humans.

The Level of Selenium and Oxidative Stress in Workers Chronically Exposed to Lead.

The possible beneficial role of selenium (Se) on the oxidative stress induced by lead (Pb) is still unclear in humans. Therefore, the aim of the present study was to explore the associations among the Se levels, chronic Pb exposure, oxidative stress parameters, and parameters characterizing the function of the antioxidant defense system in men who are occupationally exposed to Pb. Based on the median serum Se concentrations, the 324 study subjects were divided into two subgroups: a subgroup with a low Se level (L-Se) and a subgroup with a high Se level (H-Se). The levels of lead (PbB) and zinc protoporphyrin (ZPP) in the blood and the delta-aminolevulinic acid (ALA) level in the urine served as indices of Pb exposure. The PbB level was significantly lower in the H-Se group compared to that in the L-Se group by 6 %. The levels of 8-hydroxyguanosine and lipofuscin (LPS) and the activity of superoxide dismutase were significantly lower in the H-Se group compared to that in the L-Se group by 17, 19, and 11 %, respectively. However, the glutathione level (GSH) and the activities of glutathione peroxidase (GPx) and catalase were significantly higher by 9, 23, and 3 %. Spearman correlations showed positive associations between the Se level and GPx activity and GSH level. A lower serum Se level in chronically Pb-exposed subjects is associated with higher Pb blood levels and an elevated erythrocyte LPS level, which reflects the intensity of oxidative stress. Besides, in a group of Pb-exposed subjects with lower serum Se level, depleted GSH pool and decreased activity of GPx in erythrocytes were reported. However, the present results are inadequate to recommend Se supplementation for chronic lead exposure at higher doses than would be included in a normal diet except for selenium deficiency.

Telomere length, telomerase expression, and oxidative stress in lead smelters.

The negative health effects caused by lead (Pb) exposure are widely recognized; however, the molecular mechanisms remain unknown. The aim of this study was to assess the effect of occupational Pb exposure on telomere length and to investigate the potential mechanisms leading to telomere shortening. A cohort of 334 male Pb smelters (exposed group) and 60 age-adjusted males unexposed to Pb (control group) were examined. Assessments of relative telomere length (rTL) and telomerase reverse transcriptase (TERT) gene expression were performed using quantitative real-time polymerase chain reactions. Assessments of whole blood Pb (B-Pb) and whole blood cadmium (B-Cd) concentrations and serum selenium concentration (S-Se) were performed using graphite furnace atomic absorption spectrometry. We analyzed total oxidation status (TOS), lipid hydroperoxides (LHPs), malonylodialdehyde levels in serum (MDA) and in erythrocyte hemolysates (MDA-hgb), and 8-hydroxy-deoxy-guanosine (8-OHdG). The Pb-exposed group had higher B-Pb values and shorter rTL than the control group. The arithmetic mean values calculated for B-Pb were 33 µg/dL versus 2.2 µg/dL (p < 0.0001), and the rTL values were 0.928 and 1.126 relative units (p = 0.001), respectively, for the Pb-exposed and control groups. The rTL was found to gradually shorten in response to the increasing levels of Pb exposure. The Pb-exposed group also demonstrated a higher level of oxidative stress than the control group, which was indicated by increased TOS and MDA-hgb values. rTL was negatively associated with parameters that indicated increased oxidative stress, including TOS (Spearman's rank coefficient (rS) = -0.16; p < 0.01) and MDA-hgb (rS = -0.17; p < 0.001). No correlations were found between rTL and B-Cd and S-Se or smoking and MDA and LHP levels. Univariate analysis indicated that B-Pb was associated with decreased rTL (ß =-0.0041; p = 0.0063) and that the association between B-Pb and rTL remained significant, even when adjusting for age (ß = -0.0041; p = 0.0065) and in multivariable-adjusted model (ß = -0.0042; p = 0.0063). In conclusion, occupational Pb exposure resulted in decreased rTL and may represent a mechanism that contributes to Pb-related diseases.

Interaction between blood selenium concentration and a levels of oxidative stress and antioxidative capacity in healthy children.

The study aimed at defining the relationship between blood selenium concentration (Se-B) and levels of oxidative stress and antioxidative capacity in healthy children. The studies were conducted on 337 children (mean age: 8.53±1.92 years). The groups of individuals with Se-B <1st quartile (group I, Se-B<70µg/L), with Se-B fitting the range of 1st quartile and median (group II, Se-B: 70-76.9µg/L), with Se-B between the median and 3rd quartile (group III, Se-B: 77-83.9µg/L) and those with Se-B above the 3rd quartile (group IV, Se-B≥84µg/L) were distinguished. Level of oxidative stress was defined using determination of urine malonyldialdehyde concentration (MDA) and urine 8-hydroxy-2-deoxyguanosine concentration (8-OHdg). Urine total antioxidant status (TAS) was determined. In group IV TAS was significantly higher than in groups I-III. A positive correlation was detected between Se-B and TAS. In healthy children an appropriately high Se-B seems to ensure higher total antioxidative status.

The effect of occupational lead exposure on blood levels of zinc, iron, copper, selenium and related proteins.

The study objective was to evaluate the effect of occupational lead exposure on blood concentrations of zinc, iron, copper, selenium and proteins related to them, such as transferrin, caeruloplasmin and haptoglobin. The examined group consisted of 192 healthy male employees of zinc-lead works. By the degree of lead exposure, the exposed group was subdivided into three subgroups. The control group was composed of 73 healthy male administrative workers. The markers of lead exposure (blood levels of lead and zinc protoporphyrin) were significantly elevated in the exposed group compared with the control group. Additionally, concentrations of copper and caeruloplasmin were raised. The significant increase in haptoglobin level was observed only in the low exposure group. Selenium levels were significantly decreased, whereas iron, zinc and transferrin levels were unchanged in the exposed group compared with the control group. There were positive correlations between the lead toxicity parameters and the copper and caeruloplasmin levels. In conclusion, the effect of occupational exposure to lead on the metabolism of trace metals appears to be limited. However, significant associations between lead exposure and levels of copper and selenium were shown. Changed levels of positive acute-phase proteins, such as caeruloplasmin and haptoglobin, were also observed.

Blood selenium concentration in a selected population of children inhabiting industrial regions in Upper Silesia (Poland).

PURPOSE: Present study aimed at determining blood selenium concentration (Se-B) in a selected population of children inhabiting industrial regions. METHODS: The studies were conducted on a group of 267 children inhabiting industrial regions in Upper Silesia (Poland). Determination of Se-B was performed using hydride generation atomic absorption technique. RESULTS: In the studied group of children mean Se-B amounted to 76.75±12.52µg/L. Only in 38.20% of studied children the estimated Se-B could be regarded as an optimal. Children with underweight (BMI<15th centile) manifested a significantly lower Se-B than children with BMI within the normal range (BMI 15-85th centile). In the entire study group of children a significant positive linear correlation was disclosed between BMI and Se-B (r=0.16, p<0.05). Regression analysis demonstrated that in the studied subgroup of children (with normal height, body mass and BMI) a higher BMI represented an independent factor of Se-B increase and a more pronounced age an independent factor of Se-B decrease. Moreover, maternal education represented an independent factor of Se-B increase in the studied group of children (with normal height, body mass and BMI). CONCLUSIONS: Se-B in the studied group children from industrial area in Upper Silesia corresponded with the lower range of blood selenium concentrations noted in recent years in other populations. A negative relationship was documented between age and Se-B and a positive relationship between BMI of a child and maternal education on one hand and Se-B of a child on the other.

A multicenter study on the audiometric findings of styrene-exposed workers.

OBJECTIVE: The objective of this study was to evaluate hearing loss among workers exposed to styrene, alone or with noise. DESIGN: This cross-sectional study was conducted as part of NoiseChem, a European Commission 5th Framework Programme research project, by occupational health institutes in Finland, Sweden, and Poland. STUDY SAMPLE: Participants' ages ranged from 18-72 years (n = 1620 workers). Participants exposed to styrene, alone or with noise, were from reinforced fiberglass products manufacturing plants (n = 862). Comparison groups were comprised of workers noise-exposed (n = 400) or controls (n = 358). Current styrene exposures ranged from 0 to 309 mg/m(3), while mean current noise levels ranged from 70-84 dB(A). Hearing thresholds of styrene-exposed participants were compared with Annexes A and B from ANSI S3.44, 1996. RESULTS: The audiometric thresholds of styrene exposed workers were significantly poorer than those in published standards. Age, gender, and styrene exposure met the significance level criterion in the multiple logistic regression for the binary outcome 'hearing loss' (P = 0.0000). Exposure to noise (<85 dBA p = 0.0001; ≥85 dB(A) p = 0.0192) interacted significantly with styrene exposure. CONCLUSIONS: Occupational exposure to styrene is a risk factor for hearing loss, and styrene-exposed workers should be included in hearing loss prevention programs.