-
1.
The Effect of Resveratrol on Blood Lipid Profile: A Dose-Response Meta-Analysis of Randomized Controlled Trials.
Cao, X, Liao, W, Xia, H, Wang, S, Sun, G
Nutrients. 2022;14(18)
-
-
-
Free full text
Plain language summary
It is well known that cardiovascular disease is a leading cause of death. Imbalances in the blood lipid levels, such as elevation of total cholesterol, Triglycerides and LDL cholesterol, may increase the risk of cardiovascular disease. It has been shown that resveratrol, a polyphenol found in grapes, blueberries, mulberries, raspberries, peanuts, and knotweeds, has protective effects against cardiovascular disease. In this meta-analysis, 17 randomised controlled trials were included, with varying durations of 4 to 48 weeks and intervention dosages ranging from 10 to 3000 mg/day. According to the results of this meta-analysis, Resveratrol supplementation significantly reduced total cholesterol, triglycerides, and LDL cholesterol, but not HDL cholesterol. In addition, the reduction in LDL cholesterol was more significant in type 2 diabetic patients when resveratrol was supplemented for 12 weeks or more. A crucial factor in determining the effectiveness of resveratrol supplementation is its dosage. High doses over 500 mg/day were found to have the opposite effect of increasing body mass index and body weight and suppressing the cardioprotective effect. The effects of different dosages and durations of resveratrol supplementation on cardiometabolic health require further robust research. Healthcare professionals may use the results of this study to understand the importance of careful consideration when supplementing resveratrol as a nutraceutical.
Abstract
(1) Background: The effects of resveratrol on blood lipids are controversial. Whether there is a dose-response of the lipid profile upon resveratrol supplementation is unknown. (2) Methods: This dose-response meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of resveratrol supplementation on lipid profile. A systematical and comprehensive search of several databases was conducted by 30 June 2022. (3) Results: The results indicated that the intake of resveratrol could significantly decrease the total cholesterol (TC) (mean difference = -10.28; 95%CI: -13.79, -6.76, p < 0.001), triglyceride (TG) (Mean difference = -856; 95%CI: -12.37, -4.75, p < 0.001) and low-density lipoprotein cholesterol (LDL-C) (mean difference = -5.69; 95%CI: -11.07, -0.31, p = 0.038) level, but did not alter the level of high-density lipoprotein cholesterol (HDL-C). In the non-linear dose-response analysis, we observed a significant effect of the supplementation dosage on the level of LDL-C (p-nonlinearity = 0.002). Results from the sub-group analysis showed that the reduction of LDL-C was more significant in the trials with a duration of ≥12 weeks and in subjects with type 2 diabetes mellitus. (4) Conclusion: Findings from this study suggest that resveratrol may be beneficial to reduce TC, TG, and LDL-C levels in the blood. The dosage of the resveratrol intervention is an essential factor that affects the level of LDL-C.
-
2.
The Effect of Walnut Intake on Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Alshahrani, SM, Mashat, RM, Almutairi, D, Mathkour, A, Alqahtani, SS, Alasmari, A, Alzahrani, AH, Ayed, R, Asiri, MY, Elsherif, A, et al
Nutrients. 2022;14(21)
-
-
-
Free full text
Plain language summary
The prevalence of cardiovascular disease increases as the modifiable risk factors increase, such as metabolic syndrome, obesity, type 2 diabetes, dyslipidaemia, and high blood pressure. Walnuts are a rich source of anti-inflammatory polyunsaturated fatty acids and omega-3 fatty acids. Walnuts are also known for their antioxidant properties and have been found to improve dyslipidaemia by reducing total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c). This systematic review and meta-analysis of thirteen randomised controlled trials evaluated the effects of walnut intake on lipid profile. Most of the included studies used walnut dosage ranging from 15 g to 99 g/day for six to sixteen weeks of intervention. The results of this systematic review and meta-analysis showed significant improvements in TC, LDL-c, and triglyceride (TG) levels. Subgroup analysis revealed greater improvement in TC, LDL-c, and TG in overweight and other comorbidities but had normal levels of TC and LDL-C. Additionally, female participants showed greater improvements in TG levels, followed by the walnut intervention. Intervention duration also affected the beneficial effect of the walnut intervention. Further robust studies are required to determine the effects of walnut intake on cardiovascular disease risk reduction due to the high heterogeneity between the included studies. However, healthcare professionals can use the results of this research to understand the benefits of including walnuts as part of a healthy diet and their impact on reducing dyslipidaemia.
Abstract
Cardiovascular diseases (CVD) are the leading causes of death worldwide. Dyslipidemia is a cardiometabolic risk factor of CVD, yet it can be modifiable. Walnuts have been suggested as a dietary intervention to improve the lipid profile. Therefore, we reviewed the literature to assess the evidence linking walnut intake to the improvement of blood lipids, including total cholesterol (TC), low-density lipoprotein (LDL-C) cholesterol, high-density lipoprotein (HDL-C) cholesterol, and triglycerides (TG). PubMed and Embase databases were searched from 2010 up to March 2022. We limited our search to randomized controlled trials conducted on humans and published in English during the specified period. Cochrane's risk of bias tool for interventional studies was used. A random-effects model was used for the meta-analysis, and weighted mean differences were obtained (WMD) Thirteen trials from the U.S., Europe, and Asia were included. Walnut intake was associated with significant reductions in TC (WMD: -8.58 mg/dL), LDL-C (WMD: -5.68 mg/dL), and TG (WMD: -10.94 mg/dL). Walnut consumption was not associated with HDL-C. Subgroup analysis showed that overweight/obese and those with comorbidities had more lipid improvement. A longer trial duration did result in further improvements. However, our results may be prone to bias due to extraneous confounding factors. Additionally, levels of heterogeneity were considerable for some outcomes of interest. Results from this meta-analysis provide evidence for the health benefits of walnuts on blood lipids. Walnuts possibly reduce the risk of CVD; thus, they can be successfully added to a dietary pattern to enhance health benefits.
-
3.
Adverse Effects of Excessive Zinc Intake in Infants and Children Aged 0-3 Years: A Systematic Review and Meta-Analysis.
Ceballos-Rasgado, M, Lowe, NM, Mallard, S, Clegg, A, Moran, VH, Harris, C, Montez, J, Xipsiti, M
Advances in nutrition (Bethesda, Md.). 2022;13(6):2488-2518
-
-
-
Free full text
-
Plain language summary
The upper limit of a nutrient’s intake has been defined as the maximum intake from food, water, and supplements that is unlikely to pose risk of adverse health effects to most individuals in the general population. The aim of this study was to determine the levels of zinc intake at which adverse effects are observed in children aged 0–3 years. This study is a systematic review and meta-analysis of fifty-eight articles from fifty-five studies. Almost all studies were randomised controlled studies (n=52) and the rest were quasi-experimental studies. Results show: - that zinc supplementation had a significant adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, haemoglobin, haematocrit, and the odds of anaemia in ≥1 of the subgroups of pooled data. - a significant reduction of the lactulose:mannitol ratio. - that there weren’t significant effects of zinc supplementation on c-reactive protein, erythrocyte superoxide dismutase [antioxidant enzyme], zinc protoporphyrin [chemical compound], blood cholesterol, or iron deficiency anaemia Authors conclude that the recommended maximum zinc doses might need to be adjusted for children at risk or recovering from iron or copper deficiency. Additionally, the study’s findings may be used to undertake dose–response modelling to estimate tolerable upper intake levels of zinc in children aged 0–3 years.
Abstract
Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of zinc intake for young children are extrapolated from adult data. This systematic review (PROSPERO; registration no. CRD42020215187) aimed to determine the levels of zinc intake at which adverse effects are observed in young children. Studies reporting potential adverse effects of zinc intake in children aged 0-3 y were identified (from inception to August 2020) in MEDLINE, Embase, and the Cochrane Library, with no limits on study design. Adverse clinical and physical effects of zinc intake were synthesized narratively, and meta-analyses of biochemical outcomes were conducted. Random effects models were used to generate forest plots to examine the evidence by age category, dose, dose duration, chemical formula of zinc, and zinc compared with placebo. The Joanna Briggs Institute Critical Appraisal Checklist, Cochrane Risk of Bias 2, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline were employed to assess risk of bias and to appraise the certainty of evidence. Fifty-eight studies assessed possible adverse effects of zinc doses ranging from 3 to 70 mg/d. Data from 39 studies contributed to meta-analyses. Zinc supplementation had an adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, hemoglobin, hematocrit, and the odds of anemia in ≥1 of the subgroups investigated. Lactulose:mannitol ratio was improved with zinc supplementation, and no significant effect was observed on C-reactive protein, erythrocyte superoxide dismutase, zinc protoporphyrin, blood cholesterol, and iron deficiency anemia. The certainty of the evidence, as assessed using GRADE, was very low to moderate. Although possible adverse effects of zinc supplementation were observed in some subgroups, it is unclear whether these findings are clinically important. The synthesized data can be used to undertake a dose-response analysis to update current guidelines of ULs of zinc intake for young children.
-
4.
Astaxanthin Influence on Health Outcomes of Adults at Risk of Metabolic Syndrome: A Systematic Review and Meta-Analysis.
Leung, LY, Chan, SM, Tam, HL, Wong, ES
Nutrients. 2022;14(10)
-
-
-
Free full text
Plain language summary
Metabolic syndrome is a term used to describe a combination of three or more health issues that can increase the risk of cardiovascular disease by 70%. Risk factors include hypertension, hyperglycaemia, obesity, and dyslipidaemia. Astaxanthin is a powerful antioxidant that can potentially reduce the risk of metabolic syndrome. This systematic review and meta-analysis included seven double-blinded randomised controlled trials that evaluated the beneficial effects of Astaxanthin in reducing the risk factors associated with metabolic syndrome. More than eight weeks of daily ≤6 mg Astaxanthin supplementation significantly reduced systolic blood pressure, total cholesterol, triglycerides, and LDL cholesterol. The therapeutic value of Astaxanthin supplementation requires long-term robust research since studies included in this study are highly heterogeneous in terms of the intervention period, the dosage of the supplements, participant health, and sample size. This study can assist healthcare professionals in understanding the beneficial effects of Astaxanthin supplements on people with metabolic syndrome.
Abstract
The use of medication is effective in managing metabolic syndrome (MetS), but side effects have led to increased attention on using nutraceuticals and supplements. Astaxanthin shows positive effects in reducing the risk of MetS, but results from individual studies are inconclusive. This systematic review summarizes the latest evidence of astaxanthin in adults with risk factors of MetS. A systematic search of English and Chinese randomized controlled trials in 14 electronic databases from inception to 30 June 2021 was performed. Two reviewers independently screened the titles and abstracts, and conducted full-text review, quality appraisal, and extraction of data. Risk of bias was assessed by PEDro. A total of 7 studies met the inclusion criteria with 321 participants. Six studies were rated to have excellent methodological quality, while the remaining one was rated at good. Results show marginal effects of astaxanthin on reduction in total cholesterol and systolic blood pressure, and a significant attenuating effect on low-density lipoprotein cholesterol. Further robust evidence is needed to examine the effects of astaxanthin in adults at risk of MetS.
-
5.
Effects of the 5:2 intermittent fasting diet on non-alcoholic fatty liver disease: A randomized controlled trial.
Kord Varkaneh, H, Salehi Sahlabadi, A, Găman, MA, Rajabnia, M, Sedanur Macit-Çelebi, M, Santos, HO, Hekmatdoost, A
Frontiers in nutrition. 2022;9:948655
-
-
-
Free full text
Plain language summary
Non-alcoholic fatty liver disease (NAFLD) is associated with modifiable risk factors such as obesity, diabetes and metabolic syndrome. The 5:2 diet is an intermittent fasting regimen in which you fast for two days and eat liberally for five days per week. Time-restricted eating or intermittent fasting is a great way to limit energy intake and manage metabolic markers, making fasting diets like the 5:2 a viable option for the treatment of NAFLD. In this study, fifty patients with NAFLD were randomly assigned to either the intermittent fasting (5:2) or the control group. In the 5:2 group, the intervention resulted in a modest reduction in calorie intake. Participants on the 5:2 diet showed significant improvements in biomarkers of NAFLD, inflammatory markers, and body composition after 12 weeks of intervention. An evaluation of the effectiveness of a 5:2 diet on improving lipid profiles and diabetes requires further robust research. This study provides healthcare professionals insight into the benefits of implementing intermittent fasting as a cost-effective and safe therapeutic method.
Abstract
Background and aims: Dietary regimens are crucial in the management of non-alcoholic fatty liver disease (NAFLD). The effects of intermittent fasting (IF) have gained attention in this regard, but further research is warranted. Thus, we aimed to ascertain the overall effects of the 5:2 IF diet (5 days a week of normal food intake and 2 consecutive fasting days) in patients with NAFLD compared to a control group (usual diet). Methods and results: A 12-week randomized controlled trial was performed to evaluate the effects of the 5:2 IF diet on anthropometric indices, body composition, liver indices, serum lipids, glucose metabolism, and inflammatory markers in patients with NAFLD. The IF group (n = 21) decreased body weight (86.65 ± 12.57-82.94 ± 11.60 kg), body mass index (30.42 ± 2.27-29.13 ± 1.95 kg/m2), waist circumference (103.52 ± 6.42-100.52 ± 5.64 cm), fat mass (26.64 ± 5.43-23.85 ± 5.85 kg), fibrosis (6.97 ± 1.94-5.58 ± 1.07 kPa), steatosis scores/CAP (313.09 ± 25.45-289.95 ± 22.36 dB/m), alanine aminotransferase (41.42 ± 20.98-28.38 ± 15.21 U/L), aspartate aminotransferase (34.19 ± 10.88-25.95 ± 7.26 U/L), triglycerides (171.23 ± 39.88-128.04 ± 34.88 mg/dl), high-sensitivity C-reactive protein (2.95 ± 0.62 -2.40 ± 0.64 mg/L), and cytokeratin-18 (1.32 ± 0.06-1.19 ± 0.05 ng/ml) values compared to the baseline and the end of the control group (n = 23)-p ≤ 0.05 were considered as significant. However, the intervention did not change the levels of high-density lipoprotein cholesterol, total cholesterol, low-density lipoprotein cholesterol, fasting blood sugar, insulin, HOMA-IR, and total antioxidant capacity. Conclusion: Adhering to the 5:2 IF diet can reduce weight loss and related parameters (fat mass and anthropometric indicators of obesity), as well as hepatic steatosis, liver enzymes, triglycerides, and inflammatory biomarkers in patients with NAFLD.
-
6.
An oleuropein-based dietary supplement may improve joint functional capacity in older people with high knee joint pain: findings from a multicentre-RCT and post hoc analysis.
Horcajada, MN, Beaumont, M, Sauvageot, N, Poquet, L, Saboundjian, M, Costes, B, Verdonk, P, Brands, G, Brasseur, J, Urbin-Choffray, D, et al
Therapeutic advances in musculoskeletal disease. 2022;14:1759720X211070205
-
-
-
Free full text
Plain language summary
Mobility is an important factor for the quality of life and healthy ageing. Yet, most people as they age will experience some degree of mobility issue, typically linked to problems with joints, bones or muscles. Current medical treatments focus on the management of pain and discomfort with anti-inflammatory drugs and pain relief. However, chronic use of these medications is associated with many side effects. Olive leaf extract (OLE) is a rich source of anti-inflammatory and antioxidant compounds such as oleuropein. Animal studies of OLE showed it had promising effects on inflammation and age-related joint degeneration, and in clinical studies, it was demonstrated to preserve bone mineral density. This 6-month randomized placebo-controlled trial investigated the use of 125mg OLE on knee pain, discomfort and loss of mobility in 124 elderly subjects over 55 who experienced mild to moderate pain during or after physical activity in the absence of diagnosed underlying conditions such as osteoarthritis. The outcome was tracked by scoring questionnaires and blood samples to monitor inflammatory markers, as well as urinary samples to assess compliance. At the end of the trial, there was no significant difference in pain or inflammatory markers, apart from a decline in Prostaglandin E2 in the OLE takers. An adjusted analysis showed that whereby people with mild to moderate pain did not experience any benefits, a significant effect was seen in people who had higher levels of baseline pain to begin with. Due to the good safety profile of OLE, it may be a suitable intervention for those candidates. Larger scale trials may help to enhance these findings.
Abstract
OBJECTIVES To investigate a 6-month intervention with an olive leaf extract (OLE) on knee functionality and biomarkers of bone/cartilage metabolism and inflammation. DESIGN This randomized, double-blind, placebo-controlled, multi-centric trial included 124 subjects with knee pain or mobility issues. Subjects received twice a day one capsule of placebo or 125 mg OLE (Bonolive™, an OLE containing 50 mg of oleuropein) for 6 months. The co-primary endpoints were Knee injury and Osteoarthritis Outcome Score (KOOS) and serum Coll2-1NO2. The secondary endpoints were the subscales of the KOOS, knee pain VAS at rest and at walking, OARSI core set of performance-based tests and multiple inflammatory and bone or cartilage remodeling serum biomarkers and concentration of oleuropein's metabolites in urine. RESULTS At 6 months, OLE group was not efficient on global KOOS score, changes of inflammatory and cartilage remodeling biomarkers compared to placebo. Post hoc analyses demonstrated a large and significant treatment effect of OLE in a sub-group of subjects with high walking pain at baseline (p = 0.03). This was observed at 6 months for the global KOOS score, and each different subscale and for pain at walking (p = 0.02). OLE treatment was well tolerated. CONCLUSION OLE was not effective on joint discomfort excepted in a sub-group of subjects with high pain at treatment initiation. As oleuropein is well tolerated, OLE can be used to relieve knee joint pain and enhance mobility in subjects with articular pain.
-
7.
Effects of Antioxidants on Pain Perception in Patients with Fibromyalgia-A Systematic Review.
Fernández-Araque, A, Verde, Z, Torres-Ortega, C, Sainz-Gil, M, Velasco-Gonzalez, V, González-Bernal, JJ, Mielgo-Ayuso, J
Journal of clinical medicine. 2022;11(9)
-
-
-
Free full text
Plain language summary
Fibromyalgia (FM) is characterised by widespread chronic pain, fatigue, sleep disturbances, and cognitive impairment. As a result of oxidative stress, reactive oxygen species (ROS) are produced and improperly disposed of, resulting in peripheral and central sensitisations, and a reduction of the pain threshold in FM patients. It is well known that antioxidants are protective against oxidative stress and that reducing antioxidant levels can result in increased pain in patients with FM. An overview of 17 studies was conducted to evaluate the effect of antioxidant supplementation on pain perception and the appropriate duration of treatment for FM patients in this systematic review. This systematic review found that supplementation with Fibromyalgine® (Fib) (that contains vitamin C, acerola ginger root, and freeze-dried royal jelly), 300-400 gm/d of coenzyme Q10 alone in combination with Pregabalin, ferric carboxymaltose, vitamin C, E, and Nigella sativa, magnesium + amitriptyline, acetyl L-carnitine, and Sun Chlorella™ green algae are effective in reducing pain perception in FM patients. In patients with FM, alpha-lipoic acid supplementation significantly reduced pain scores. 80% of FM patients reported reduced pain after supplement treatment for at least six weeks. There is a need for further robust long-term studies to confirm the effectiveness and clinical applicability of antioxidants in the management of FM, as well as to identify the pathophysiology of FM. This research may, however, be used by healthcare professionals to gain a better understanding of the potential benefits of antioxidants in the treatment of pain associated with FM.
Abstract
In recent years, antioxidant supplements have become popular to counteract the effects of oxidative stress in fibromyalgia and one of its most distressing symptoms, pain. The aim of this systematic review was to summarize the effects of antioxidant supplementation on pain levels perceived by patients diagnosed with fibromyalgia. The words used respected the medical search terms related to our objective including antioxidants, fibromyalgia, pain, and supplementation. Seventeen relevant articles were identified within Medline (PubMed), Scopus, Web of Science (WOS), the Cochrane Database of Systematic Review, and the Cochrane Central Register of Controlled Trials. This review found that antioxidant supplementation is efficient in reducing pain in nine of the studies reviewed. Studies with a duration of supplementation of at least 6 weeks showed a benefit on pain perception in 80% of the patients included in these studies. The benefits shown by vitamins and coenzyme Q10 are remarkable. Further research is needed to identify the effects of other types of antioxidants, such as extra virgin olive oil and turmeric. More homogeneous interventions in terms of antioxidant doses administered and duration would allow the effects on pain to be addressed more comprehensively.
-
8.
MitoQ supplementation augments acute exercise-induced increases in muscle PGC1α mRNA and improves training-induced increases in peak power independent of mitochondrial content and function in untrained middle-aged men.
Broome, SC, Pham, T, Braakhuis, AJ, Narang, R, Wang, HW, Hickey, AJR, Mitchell, CJ, Merry, TL
Redox biology. 2022;53:102341
-
-
-
Free full text
Plain language summary
Exercise-induced stressors trigger an acute and transient upregulation of gene expression in skeletal muscle that, if reinforced by repeated exercise bouts as part of an exercise training program, results in phenotypic adaptations that improve skeletal muscle function. The aim of this study was to investigate the effect of mitochondria-targeted coenzyme Q10 (mitoquidone; MitoQ) supplementation on a) skeletal muscle mitochondrial and antioxidant gene transcriptional response to acute high-intensity exercise and b) skeletal muscle mitochondrial content and function following exercise training. This study is a double-blind, placebo-controlled parallel design study. Participants were randomised to receive MitoQ or an identical placebo. Participants were instructed to consume one tablet per day 30 min before breakfast for 10 days before the acute exercise trial until completion of the final study visit. Results show that the acute exercise-induced transcriptional response and training-induced mitochondrial adaptations in skeletal muscle are not attenuated by MitoQ supplementation. Furthermore, MitoQ enhances the effect of exercise training on peak power achieved during a ramp-incremental exercise test. Authors conclude that training-induced increases in peak power are enhanced following MitoQ supplementation. However, these effects do not appear to be related to an effect of MitoQ supplementation on exercise-induced oxidative stress or training-induced mitochondrial biogenesis in skeletal muscle.
Abstract
The role of mitochondrial ROS in signalling muscle adaptations to exercise training has not been explored in detail. We investigated the effect of supplementation with the mitochondria-targeted antioxidant MitoQ on a) the skeletal muscle mitochondrial and antioxidant gene transcriptional response to acute high-intensity exercise and b) skeletal muscle mitochondrial content and function following exercise training. In a randomised, double-blind, placebo-controlled, parallel design study, 23 untrained men (age: 44 ± 7 years, VO2peak: 39.6 ± 7.9 ml/kg/min) were randomised to receive either MitoQ (20 mg/d) or a placebo for 10 days before completing a bout of high-intensity interval exercise (cycle ergometer, 10 × 60 s at VO2peak workload with 75 s rest). Blood samples and vastus lateralis muscle biopsies were collected before exercise and immediately and 3 h after exercise. Participants then completed high-intensity interval training (HIIT; 3 sessions per week for 3 weeks) and another blood sample and muscle biopsy were collected. There was no effect of acute exercise or MitoQ on systemic (plasma protein carbonyls and reduced glutathione) or skeletal muscle (mtDNA damage and 4-HNE) oxidative stress biomarkers. Acute exercise-induced increases in skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) mRNA expression were augmented in the MitoQ group. Despite this, training-induced increases in skeletal muscle mitochondrial content were similar between groups. HIIT-induced increases in VO2peak and 20 km time trial performance were also similar between groups while training-induced increases in peak power achieved during the VO2peak test were augmented in the MitoQ group. These data suggest that training-induced increases in peak power are enhanced following MitoQ supplementation, which may be related to the augmentation of skeletal muscle PGC1α expression following acute exercise. However, these effects do not appear to be related to an effect of MitoQ supplementation on exercise-induced oxidative stress or training-induced mitochondrial biogenesis in skeletal muscle.
-
9.
Effect of mitochondrial-targeted antioxidants on glycaemic control, cardiovascular health, and oxidative stress in humans: A systematic review and meta-analysis of randomized controlled trials.
Mason, SA, Wadley, GD, Keske, MA, Parker, L
Diabetes, obesity & metabolism. 2022;24(6):1047-1060
-
-
-
-
Free full text
-
Plain language summary
Reactive oxygen species (ROS) are free radical oxygen molecules produced by mitochondria, which cause molecular damage known as oxidative stress. Chronic diseases such as diabetes, heart disease, cancer, and Parkinson's disease are more likely to develop when ROS levels are elevated. Mitochondrial‐targeted antioxidants (mitoAOX) may be effective in treating chronic diseases by targeting mitochondrial ROS. In this systematic review and meta-analysis, 19 randomised controlled trials were included to evaluate the effects of mitoAOXs on glycaemic control, cardiovascular health, and oxidative stress in humans. The evidence is limited, but there were improvements in endothelial function, blood pressure, oxidative stress, and functional capacity. The mitoAOX agents, dosage, and participant characteristics varied between the studies, making it difficult to draw conclusions. Due to the heterogeneity of studies included in this study, there is a need for larger, longer-term robust studies to investigate mitoAOXs' effects on mitochondrial ROS and markers of oxidative stress in different clinical populations. As a result of this study, healthcare professionals can gain a better understanding of mitoAOX's potential in tackling oxidative stress. However, caution must be exercised before implementing it as a therapeutic strategy due to concerns over possible adverse effects and a low evidence certainty.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Mitochondria are a major producer of reactive oxygen species (ROS) in cells. Excess mitochondrial ROS has been implicated in the pathophysiology of various chronic diseases including Parkinson’s disease, cardiovascular disease (CVD), Type 2 diabetes and cancer.
- This review reported that there is limited evidence to support the use of mitoAOXs in the management of glycaemic control and cardiovascular health. However, there are promising findings on the effect of mitoAOXs on endothelial function that warrant consideration and further investigation in target clinical population groups.
Evidence Category:
-
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
X
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Background
A systematic review and meta-analysis was conducted to evaluate the current evidence from randomised control trials (RCTs) in humans on the effects of mitochondrial-targeted antioxidant (mitoAOXs) on glycaemic control, cardiovascular health, and oxidative stress.
Methodology
19 Randomised control trials (n= 884 participants) using mitoAOXs (including Elamipretide, MitoQ and MitoTEMPO) were included from MEDLINE-PubMed, Scopus, EMBASE and Cochrane Library databases. A Cochrane Collaboration’s tool was used to assess risk bias and to grade the quality of the trials and their certainty of the evidence.
Results
Primary clinical outcomes were:
- A quantitative analysis on glycaemic control found no significant effect for fasting glucose in response to MitoQ supplementation.
- A quantitative analysis on cardiovascular health related outcomes found a significant lowering effect of mitoAOXs brachial flow-mediated dilation (FMD) (standardized mean difference: 1.19, 95% CI: 0.28, 2.16; I2: 67%) and an improved blood pressure (standardized mean difference: -0.32, 95% CI:-0.95, 0.30; I2: 0%) in patients with atherosclerosis-related impairment of renal blood flow.
- A quantitative analysis on oxidative stress-related outcomes found no significant effect of mitoAOX on malondialdehyde or F2-Isoprostanes.
Clinical practice applications:
- The findings from this review suggest limited evidence to support the use of mitoAOX in the management of glycaemic control or cardiovascular health.
- However, there are some potential promising findings which included improved endothelial function (particularly brachial FMD) and improved blood pressure in patients with atherosclerosis-related impairment of renal blood flow.
- Based on this review, practitioners may consider recommending the use of mitoAOXs only in quite specific circumstances, namely to improve endothelial function in patients with a risk of brachial FMD or high blood pressure associated with atherosclerosis-related impairment of renal blood flow.
Considerations for future research:
- The studies included in this review were mostly one to three months in duration therefore, there is a need for long-term, follow-up studies to be conducted to better investigate these outcomes.
- Given the pathogenic factors of elevated mitochondrial ROS and oxidative stress in chronic diseases such as CVD and Type2 diabetes, further investigation is needed into the effects of mitoAOXs on mitochondrial ROS and oxidative stress markers in target clinical population groups.
- It appears that mitoAOXs may improve endothelial function, therefore further research is needed to focus on the effect of mitoAOXs on endothelial function in target clinical populations.
- Additionally, further reviews are required to provide a more comprehensive review of the safety and adverse effects of mitoAOXs.
- Furthermore, only antioxidants specific to microconidia were included in this review. It is possible that other more general acting antioxidants may have redox-related effects in mitochondria. Therefore, a more comprehensive review is needed to include all possible antioxidant compounds that have mitochondrial effect.
Abstract
AIM: To investigate the effects of mitochondrial-targeted antioxidants (mitoAOXs) on glycaemic control, cardiovascular health, and oxidative stress outcomes in humans. MATERIALS AND METHODS Randomized controlled trials investigating mitoAOX interventions in humans were searched for in databases (MEDLINE-PubMed, Scopus, EMBASE and Cochrane Library) and clinical trial registries up to 10 June 2021. The Cochrane Collaboration's tool for assessing risk of bias and Grading of Recommendations, Assessment, Development and Evaluations were used to assess trial quality and evidence certainty, respectively. RESULTS Nineteen studies (n = 884 participants) using mitoAOXs (including Elamipretide, MitoQ and MitoTEMPO) were included in the systematic review. There were limited studies investigating the effects of mitoAOXs on glycaemic control; and outcomes and population groups in studies focusing on cardiovascular health were diverse. MitoAOXs significantly improved brachial flow-mediated dilation (n = 3 trials; standardized mean difference: 1.19, 95% CI: 0.28, 2.16; I2 : 67%) with very low evidence certainty. No significant effects were found for any other glycaemic, cardiovascular or oxidative stress-related outcomes with mitoAOXs in quantitative analyses, with evidence certainty rated mostly as low. There was a lack of serious treatment-emergent adverse events with mitoAOXs, although subcutaneous injection of Elamipretide increased mild-moderate injection site-related events. CONCLUSION While short-term studies indicate that mitoAOXs are generally well tolerated, there is currently limited evidence to support the use of mitoAOXs in the management of glycaemic control and cardiovascular health. Review findings suggest that future research should focus on the effects of mitoAOXs on glycaemic control and endothelial function in target clinical population groups.
-
10.
Serum vitamin E levels and chronic inflammatory skin diseases: A systematic review and meta-analysis.
Liu, X, Yang, G, Luo, M, Lan, Q, Shi, X, Deng, H, Wang, N, Xu, X, Zhang, C
PloS one. 2021;16(12):e0261259
-
-
-
-
Free full text
Plain language summary
Vitiligo, Psoriasis, Acne and Atopic Dermatitis are chronic immune-mediated inflammatory skin conditions characterised by itchy skin. In previous studies, decreased serum vitamin E levels have been associated with an increased risk of skin diseases. Nuts, oils from plants, and vegetables contain vitamin E, which is a dietary bioactive compound that has anti-inflammatory and antioxidant properties. In this systematic review and meta-analysis, twenty case-controlled studies were included, of which thirteen specifically examined alpha-tocopherol levels. Psoriasis, Vitiligo, atopic dermatitis, and acne patient groups had significantly lower levels of serum Vitamin E than the control groups. There is no clear understanding of the pathogenesis of chronic inflammatory skin conditions. One of the underlying mechanisms is the interaction between oxidative stress and the immune system, as well as the accumulation of free radicals in the epidermal layers of the skin. As there is limited evidence regarding the benefits of Vitamin E in improving chronic inflammatory skin conditions, further robust studies are necessary. Healthcare professionals can use this research to gain a better understanding of the potential clinical applications of vitamin E in the treatment of skin disorders.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Low serum vitamin E levels are reported to be associated with several chronic inflammatory skin diseases, such as vitiligo, psoriasis, atopic dermatitis, and acne.
- Practitioners could consider vitamin E therapy in those with low serum concentrations
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
This systematic review and meta-analysis report on the association between serum vitamin E levels and chronic inflammatory skin diseases.
The review which followed PRISMA reporting guidelines, screened 892 studies. After the selection and exclusions, 20 case-control studies were included involving a total of 1172 patients.
The studies that were included focused mainly on chronic inflammatory diseases, including vitiligo, psoriasis, atopic dermatitis, and acne. Eight studies included only adults, five included only children or teenagers and six studies included adults and children. One study had no age description.
Thirteen studies stated that alpha-tocopherol was used in their investigations. However, seven studies did not describe the subunit of vitamin E.
Primary clinical outcomes were:
- Seven studies, with 351 cases and 350 controls reported that compared with the control group, vitiligo patients had lower serum vitamin E concentrations (Standard Mean Difference (SMD):0.70, 95% Cl:121-0.19.
- Six studies investigated the change of serum vitamin E levels in patients with psoriasis, with 278 cases and 257 controls. Compared with the control group, psoriasis patients had lower serum vitamin E concentrations (SMD: -2.37, 95% CI: -3.57 to -1.18).
- The serum vitamin E Levels in patients with atopic dermatitis were observed in 4 studies, with 259 cases and 307 controls. Compared with the control group atopic dermatitis patients had lower serum vitamin E concentrations (SMD: -1.08, 95% CI: -1.80 to -0.36).
Levels of serum vitamin E in acne patients were reported in 3 studies, with 284 cases and 186 controls. Compared with the control group, acne patients had lower serum concentration levels of vitamin E (SMD: -0.67, 95% CI: -1.05 to -0.30).
No publication bias was found in any association (Egger’s test >0.05), though heterogeneity was considerable in every case (I2 > 80%), though this interaction was not significant for acne (p=0.879). Associations were not split by age, or any other cofactor, however sensitivity analyses did not indicate modification of the results.
The authors also assessed the association between skin disease severity and serum vitamin E concentrations. Overall, more severe disease was associated with a lower serum vitamin E concentration (SMD -1.56, 95% CI:-2.53 to -059).
Clinical practice applications:
- Vitamin E has gained the attention of researchers as a potential adjuvant therapy for various skin disorders due to its excellent antioxidant and anti-inflammatory properties.
- This review reports on the low levels of serum vitamin E found in patients with vitiligo, psoriasis, atopic dermatitis, and acne, and also suggests that serum concentrations of vitamin E are lower in those with more severe disease. Based on these findings, practitioners could therefore consider investigating the serum vitamin E levels of patients with inflammatory skin diseases and consider including vitamin E in their treatment protocols if their serum vitamin E levels are low.
Considerations for future research:
- The small number of studies in this review indicates the need for further research to be done on vitamin E and inflammatory skin diseases.
- Although there are reports on the antioxidant and anti-inflammatory properties of vitamin E, further investigations are needed to determine the exact mechanism of action in inflammatory skin diseases.
- Additionally, further investigation is needed to evaluate which chemical forms of vitamin E and their dosage amounts have beneficial effects on inflammatory skin diseases.
Abstract
BACKGROUND Vitamin E has long been linked to skin health, including all of its possible functions in cosmetic products, to its roles in membrane integrity and even the aging process. However, reports on the relationship between serum vitamin E levels and the risk of chronic inflammatory skin diseases have been inconsistent. We performed a systematic review and meta-analysis to evaluate the association between serum vitamin E levels and chronic inflammatory skin diseases. METHODS We searched the PubMed, Web of Science and Scopus databases, with no time limit up to 30.06.2021. Studies examining serum vitamin E levels in patients with chronic inflammatory skin diseases were selected. RESULTS Twenty articles met the inclusion criteria. Compared with controls, a lower vitamin E level was found in patients with vitiligo (SMD: -0.70, 95% CI: -1.21 to -0.19), psoriasis (SMD: -2.73, 95% CI: -3.57 to -1.18), atopic dermatitis (SMD: -1.08, 95% CI: -1.80 to -0.36) and acne (SMD: -0.67, 95% CI: -1.05 to -0.30). CONCLUSIONS Our meta-analysis showed that serum vitamin E levels were lower in patients suffering from vitiligo, psoriasis, atopic dermatitis and acne. This study highlights the need to evaluate vitamin E status to improve its level in patients with skin diseases.