-
1.
Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.
Xia, J, Yu, J, Xu, H, Zhou, Y, Li, H, Yin, S, Xu, D, Wang, Y, Xia, H, Liao, W, et al
Pharmacological research. 2023;188:106647
-
-
-
-
Free full text
-
Plain language summary
Type 2 diabetes mellitus (T2DM), characterised by sustained hyperglycaemia and insulin resistance, remains a severe driver of chronic metabolic diseases such as cardiovascular diseases. The aim of this study was to investigate and compare the efficacy of vitamin and mineral supplements in the management of glycaemic control and lipid metabolism for type 2 diabetic patients to inform clinical practice. This study is a systematic review and meta-analysis of one hundred and seventy articles with a total of 4223 adults with T2DM. Participants were randomised to either the placebo/no treatment group (n= 6345) or to the treatment group (n= 7878). Results show that: - chromium was the most effective micronutrient for decreasing fasting blood glucose and insulin resistance. - vitamin K was the top-ranked micronutrient in reducing haemoglobin A1C and fasting insulin levels. - vanadium was the top-ranked micronutrient in total cholesterol reductions. - niacin was ranked as the most effective in triglycerides reductions and increasing high-density lipoprotein cholesterol levels. - vitamin E was the top-ranked micronutrient in low-density lipoprotein cholesterol reductions. Authors conclude that micronutrient supplements especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more effective in the management of T2DM compared with other micronutrients.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Clinicians could consider the adjunctive effect of micronutrients supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements in a nutrition protocol to manage T2DM and slow or prevent its complications.
- The study authors state that the vitamin and mineral supplements under review had a statistically significant improvement, however they did not reach the study threshold for clinical significance. Therefore they advise caution in utilising micronutrient supplements in the management of glucose and lipid metabolism for T2DM.
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:
Objectives
The aim of this systematic review was to evaluate the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM).
Methodology
This systematic review is registered with PROSPERO and adhered to PRISMA-2020 guidelines for network meta-analysis
The Cochrane Collaboration’s risk-of-bias tool was used to assess eligible randomised trials
8 prespecified markers identified and assessed in this study : 1) HbA1c (%), 2) fasting blood glucose (mmol/L), 3) total cholesterol (mmol/L), 4) triglycerides (mmol/L), 5) fasting insulin (μIU/mL), 6) HOMA-IR, 7) LDL-c (mmol/L), and 8) HDL-c (mmol/L).
Results
- 170 RCT trials of 14223 participants with T2DM treated with vitamin supplements, mineral supplements, or placebo/no treatment were included
- Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively)
- Vitamin K supplements ranked best in reducing glycated haemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence
- Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%)
- Niacin supplements ranked best in triglyceride reductions and increasing high-density lipo-protein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively)
- Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%).
Conclusion
- Micronutrient supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be efficacious in managing T2DM
- It should be noted that the evidence certainty for all was low.
Clinical practice applications:
- Chromium plays an important role in carbohydrate and lipid metabolism and was the most effective micronutrient for decreasing fasting blood glucose, HbA1c, fasting insulin, and HOMA-IR reductions. More pronounced effects were seen for chromium than vitamin E, vitamin C, niacin, selenium, and magnesium supplements
- Vitamin K was the top-ranked micronutrient in reducing HbA1c and fasting insulin levels. The mechanism through which Vitamin K affects glucose metabolism is proposed as activation of the AMP-activated protein kinase/sirtuin 1, that in turn increases phosphocreatine 3-kinase and glucose transporter 2 to decrease insulin resistance and fasting glucose.
- Vanadium was the top-ranked micronutrient in total cholesterol (TC) reductions, where supplementation dosage should be carefully considered, as vanadium compounds can be moderately or highly toxic. Vanadium supplementation is only recommended in cases of vanadium deficiency or diabetes, hyperlipidemia, and hypertension, where the intake of vanadium from food should be enhanced in preference to supplementation
- Niacin was ranked as the most effective in triglyceride (TG) reductions and increasing HDL cholesterol levels. The dose of niacin could not be determined
- Vitamin E was the top-ranked micronutrient in low-density lipo- protein (LDL) cholesterol reductions.
Considerations for future research:
- Considering the clinical importance of these findings, new research is needed to get better insight into the efficacy of micronutrient supplements in managing T2DM
- Selenium homeostasis, selenoprotein, insulin signaling/secretion, and carbohydrate/lipid metabolism are linked in multiple and complex ways but the authors could not explain why chromium supplementation would lower blood glucose more effectively than selenium supplementation, and suggest more research is needed to clarify this
- While vitamin K status could be an emerging treatment target in T2DM prevention and management, it remains to be determined whether vitamin K supplementation has an advantage over other nutrients in terms of hypoglycemic effect, and further research is necessary
- The beneficial effect of vitamin E and niacin supplements regarding lipid metabolism warrant investigation through more rigorous comparative studies.
Abstract
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
-
2.
The Effect of Curcumin on Lipid Profile and Glycemic Status of Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.
Tian, J, Feng, B, Tian, Z
Evidence-based complementary and alternative medicine : eCAM. 2022;2022:8278744
-
-
-
-
Free full text
Plain language summary
Dyslipidaemia is a common comorbidity of type 2 diabetes mellitus (T2DM), which is characterised by elevated triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) level, and/or decreased high-density lipoprotein cholesterol (HDL-c) concentrate serum. Dyslipidaemia and dysglycemia interact with each other, and they are the main risk factors of macro- and microvascular diseases in T2DM. The aim of this study was to outline curcumin’s efficacy and possible uses in clinical practice. This study is a meta-analysis of nine randomised controlled trials (RCTs). A total of 604 participants (284 in the curcumin group and 281 in the control group) were included in the selected studies. The design of all trials was parallel; seven of them were double-blind RCTs, and the other two were open label RCTs. Results show that curcumin significantly decreased TG, TC, fasting blood glucose, and haemoglobin A1C levels and also led to a reduction in LDL-c and an elevation in HDL-c concentration, although with no statistical difference. Authors conclude that curcumin has promising effects on the lipid profile and glycaemic status in patients with T2DM. It indicated that curcumin might be a favourable therapeutic option for T2DM patients with mixed dyslipidaemia.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Dyslipidemia and dysglycemia interact with each other, and are risk factors of macro- and microvascular diseases in T2DM.
Although effective intervention strategies exist for improving glycemic status of T2DM patients, they often need lipid-lowering drugs simultaneously to prevent CVD.
- Novel therapeutic interventions are needed to manage dyslipidemia and dysglycemia in diabetic patients, when statin therapy to treat dyslipidemia, may increase the risk of new-onset diabetes and myopathy.
- Other clinical studies have highlighted the benefits of curcumin supplementation on lipid profile and glycemic status. Clarifying its effects is important for assessing its potential as an alternative and complementary medicine on improving the metabolic status of T2DM patients.
- Overall there is limited evidence and further research is required.
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:
Introduction
This meta-analysis aimed to evaluate the effects of curcumin on lipid profile in patients with type 2 diabetes mellitus (T2DM), including: serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-c), and/or high-density lipoprotein cholesterol (HDL-c). Fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) were also assessed.
Methods
A search was performed on Pubmed, Embase, Web of Sciences, and the Cochrane Library up to March 2022. Quality assessment of all included studies was performed.
Results
9 studies were included in the review, with a total of 604 participants (284 in the curcumin group and 281 in the control group) of mean age from 41 to 60.95 years. Curcumin forms varied among the studies including, turmeric, curcuminoids, and curcumin. The dosage of curcumin in the intervention group ranged from 80 to 2100 mg/day. The duration of intervention was between 4 weeks and 3 months in different studies.
- Effect of Curcumin on TG: A difference was observed between curcumin supplementation and control (p = 0.03), indicating curcumin could reduce serum TG.
- Effect of Curcumin on TC: The mean difference in net changes of TC between intervention and control groups was −8.91mg/dL (p = 0.001), suggesting that curcumin could decrease serum TC.
- Effect of Curcumin on LDL-C: No difference in the net change of LDL-c between intervention and control groups (p = 0.26).
- Effect of Curcumin on HDL-C: No difference in HDL-c between intervention and control groups (p = 0.56).
- Effect of Curcumin on FBG: Curcumin reduced blood glucose levels compared with control treatment (p = 0.002). The effect was greater in trials with the treatment duration >8w (p = 0.037), curcumin dose >100mg/day (p = 0.004), and with the participants receiving the other therapy (p = 0.002).
- Effect of Curcumin on HbA1c: HbA1c (%) decreased in the intervention group compared with the control group (p ≤ 0.001).
Conclusion
Curcumin has promising effects on the lipid profile and glycemic status of T2DM patients and might be a therapeutic option for T2DM patients with mixed dyslipidemia.
Clinical practice applications:
- Limitations were the small number of included studies, mostly with small sample sizes. In some studies, treatment duration was short (<2 months) and may be insufficient to see a difference in some metabolic parameters.
- The reduction of FBG and HbA1c after treatment with curcumin suggested that it improved the glycemic metabolism in the T2DM patients studied.
- Studies have shown that curcumin could promote insulin release through inducing β-cell electrical activity and lower serum glucose level via decreasing the production of hepatic glucose and increasing glucose uptake. While changes of LDL-c and HDL-c was not statistically significant, the authors note the effect of curcumin on LDL-c/HDL-c and its potential clinical significance could not be neglected.
- The reduction of dyslipidemia by curcumin supplementation could improve the glucose metabolic status of T2DM patients, and multiple molecular targets including PPAR-c, cholesteryl ester transfer protein, and lipoprotein lipase contribute to the beneficial effects of curcumin.
Considerations for future research:
- While significant heterogeneity was found in pooled analyses of TG, LDL-c, FBG, and Hb1Ac, a random-effects model revealed that trial duration, curcumin dosage, and other therapy may contribute to the variation in pooled effects, and these aspects could be discussed in future studies.
- The study found that a higher dose of curcumin was more powerful in reducing plasma TG and FBG concentrations, but further large-scale multicenter RCTs are required to confirm the clinical improvement of curcumin.
Abstract
Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder, some natural compounds are thought to be beneficial in improving the metabolic status of patients with T2DM. Curcumin is the main bioactive agent of turmeric, the impact of curcumin on T2DM is still controversial. This meta-analysis aimed to evaluate the effects of curcumin on lipids profile and glucose status in patients with T2DM. Randomized controlled trials (RCTs) examining the effects of curcumin on lipids profile and glycemic control of T2DM patients were searched in PubMed, Embase, Web of Science and Cochrane Library. Pooled estimates of weighted mean difference (WMD) were calculated between intervention and control groups using random-effects or fixed-effects model. Subgroup and sensitivity analyses were conducted to assess the effects. Nine eligible RCT with 604 subjects were included. The estimated pooled mean changes with curcumin were -18.97 mg/dL (95% CI: -36.47 to -1.47; P=0.03) for triglyceride (TG), -8.91 mg/dL (95% CI: -14.18 to -3.63, P=0.001) for total cholesterol (TC), -4.01 mg/dL (95% CI: -10.96 to 2.95, P=0.259) for low density lipoprotein cholesterol (LDL-c), 0.32 mg/dL (95% CI: -0.74 to 1.37, P=0.557) for high density lipoprotein cholesterol (HDL-c), -8.85 mg/dL (95% CI: -14.4 to -3.29, P=0.002) for fasting blood glucose (FBG), -0.54 (95% CI: -0.81 to -0.27, P ≤ 0.001) for glycated hemoglobin (HbA1c) (%) compared with controls. There was a significant heterogeneity for the influence of curcumin on TG, LDL-c, FBG and HbA1c. Subgroup analysis revealed that the heterogeneity mainly attributed to trial period, curcumin dosage and other therapy. The results of this study showed that curcumin supplementation had beneficial effects on glycemic status and some lipid parameters in patients with T2DM. Further studies with large-scale are still needed to confirm the results.
-
3.
Efficacy and Safety of Q10 Ubiquinol With Vitamins B and E in Neurodevelopmental Disorders: A Retrospective Chart Review.
Cucinotta, F, Ricciardello, A, Turriziani, L, Mancini, A, Keller, R, Sacco, R, Persico, AM
Frontiers in psychiatry. 2022;13:829516
-
-
-
-
Free full text
Plain language summary
The literature shows that oxidative stress represents a shared feature present in many brain disorders and more specifically in neurodevelopmental disorders (NDDs) including autism spectrum disorder, attention-deficit/hyperactivity disorder, and intellectual disability. The aim of this study was to verify retrospectively the clinical efficacy and safety of a metabolic support therapy (MST) with coenzyme Q10 (Q10 ubiquinol), vitamin E and complex-B vitamins in various neurodevelopmental disorders. This study is a retrospective chart review of 59 patients with NDDs. Results show that in terms of efficacy, MST was associated with clinical improvement in 45/59 (76.27%) patients. Whereas in terms of safety, side effects were mild and always manageable. Thus, this study provides retrospective evidence of efficacy and tolerability for a MST encompassing Q10-ubiquinol, vitamin E and complex-B vitamins in patients with different neurodevelopmental disorders. Authors conclude that their findings encourage further investigations of MST efficacy in neurodevelopmental disorders in order to confirm the generalisability of the study’s observations, verifying both efficacy, safety, treatment response rates and therapeutic effect size, separately in each major neurodevelopmental disorder.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Oxidative stress and mitochondrial dysfunction are reported to play a role in brain and neurological disorders.
- This retrospective chart review suggests that metabolic support therapy with Q10 ubiquinol, vitamin E and complex-B vitamins is well tolerated and produces some improvement in most patients with neurodevelopmental disorders, especially in the presence of intellectual disability.
Evidence Category:
-
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
X
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
A retrospective chart review study was conducted on the clinical efficacy and safety of metabolic support therapy (MST) with Q10 ubiquinol, vitamin E and complex-B vitamins in various neurodevelopmental disorders.
59 patients (49 Children and 6 Adults) between the ages of 2.5–39 years old diagnosed with Autism Spectrum Disorder (n=17), Autism Spectrum Disorder with co-morbid Intellectual Disability (n=19), Intellectual Disability or Global Developmental Delay (n=15), Attention-Deficit/Hyperactivity Disorder (n=3), and Intellectual Disability in Phelan-McDermid syndrome due to chr. 22q13.33 deletions (n=5) were included in the study.
Methods
Participants received 50-100mg Q10 ubiquinol, 30-60mg of vitamin E, 5.5mg-11mg of nicotinamide, 3mg-6mg of dexpanthenol, 0.45mg-0.09mg of riboflavin-5’-sodium phosphate, 5mg-10mg of inositol, pyridoxine hydrochloride, and 0.07mcg -1.40mcg of cyanocobalamin for three months. Different dosage levels were administered based on the participant’s body weight and the maximum daily allowance stated by Italy’s Ministry of Health. Patients remained on their prescribed antipsychotic medications during the study.
The Clinical Global Impression of Severity (CGI-S) scale, as well as the Clinical Global Impression of Improvement (CGI-I) scale was assessed by experienced Child and Adolescent or Adult Psychiatrists.
The clinical diagnosis was further confirmed using the Autism Diagnostic Observation Schedule – 2nd ed (ADOS-2) and the Autism Diagnostic Interview-Revised (ADIR) for ASD, the Griffiths Mental Development Scale (GMDS) for GDD, a cognitive test (Leiter-R,WPPSI-III,WISC-IV,WAISIV) for ID, the Conners Parent Rating Scale (CPRS) also in Teacher version (TRF) and the Batteria Italiana per l’ADHD (BIA) for ADHD.
At the endpoint, 45/59 (76.2%) of the subjects completed the study. No reasons were given for dropouts.
Results
Primary clinical outcomes were:
- Most widespread improvements were recorded in cognition (n=26 44,1%), adaptive functioning (n=26 44,1%) and social motivation (n=19 32.2%).
- Based on clinical chart reviews 45/59 (76.27%) patients responded to MST according to Clinical Global Impression of Severity scores.
- One 13-year-old boy with an intellectual disability, gained over 20 IQ points after consuming metabolic support therapy for 6 months.
- Mild side effects of hyperactivity and insomnia were reported in 18/59 (30%) of patients.
Clinical practice applications:
- Pharmacological treatments are prescribed to correct comorbid symptoms like sleep disorders, aggressiveness, and irritability in neurodevelopmental disorders like ASD. The efficacy of these treatments displays great interindividual variability depending not only on the treatment approach, therapist experience, and therapeutic setting but also on the genetic background of the patient.
- Oxidative stress and mitochondrial dysfunction have been described in many different brain and neurological disorders.
- Minimising the mitochondrial dysfunction produced by oxidative stress damage in brain disorders, while not directly correcting the primary mechanism responsible for the pathology, may nonetheless help to improve the clinical condition, acting as an indirect therapy.
- This study provides preliminary evidence of the efficacy and tolerability of a ‘metabolic support therapy’ encompassing Q10- ubiquinol, Vitamin E and complex-B vitamins in patients with different neurological disorders.
Considerations for future research:
- This study was based on a retrospective design using a small sample size.
- Randomised controlled trials for each single neurodevelopmental disorder are needed to conclusively demonstrate the efficacy of these mitochondrial bioenergetic and antioxidant agents and to estimate their therapeutic effect size.
Abstract
Increased oxidative stress and defective mitochondrial functioning are shared features among many brain disorders. The aim of this study was to verify retrospectively the clinical efficacy and safety of a metabolic support therapy with Q10 ubiquinol, vitamin E and complex-B vitamins in various neurodevelopmental disorders. This retrospective chart review study included 59 patients (mean age 10.1 ± 1.2 y.o., range 2.5-39 years; M:F = 2.47:1), diagnosed with Autism Spectrum Disorder (n = 17), Autism Spectrum Disorder with co-morbid Intellectual Disability (n = 19), Intellectual Disability or Global Developmental Delay (n = 15), Attention-Deficit/Hyperactivity Disorder (n = 3) and Intellectual Disability in Phelan-McDermid syndrome due to chr. 22q13.33 deletion (n = 5). After a minimum of 3 months of therapy, a positive outcome was recorded in 45/59 (76.27%) patients, with Clinical Global Impression-Improvement scores ranging between 1 ("very much improved") and 3 ("minimally improved"). The most widespread improvements were recorded in cognition (n = 26, 44.1%), adaptative functioning (n = 26, 44.1%) and social motivation (n = 19, 32.2%). Improvement rates differed by diagnosis, being observed most consistently in Phelan-McDermid Syndrome (5/5, 100%), followed by Intellectual Disability/Global Developmental Delay (13/15, 86.7%), Autism Spectrum Disorder with co-morbid Intellectual Disability (15/19, 78.9%), Autism Spectrum Disorder (11/17, 64.7%) and ADHD (1/3, 33.3%). No significant adverse event or side effect leading to treatment discontinuation were recorded. Mild side effects were reported in 18 (30.5%) patients, with the most frequent being increased hyperactivity (9/59, 15.3%). This retrospective chart review suggests that metabolic support therapy with Q10 ubiquinol, vitamin E and complex-B vitamins is well tolerated and produces some improvement in the majority of patients with neurodevelopmental disorders, especially in the presence of intellectual disability. Randomized controlled trials for each single neurodevelopmental disorder are now warranted to conclusively demonstrate the efficacy of these mitochondrial bioenergetic and antioxidant agents and to estimate their therapeutic effect size.
-
4.
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.
-
5.
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.
-
6.
Zinc supplementation affects favorably the frequency of migraine attacks: a double-blind randomized placebo-controlled clinical trial.
Ahmadi, H, Mazloumi-Kiapey, SS, Sadeghi, O, Nasiri, M, Khorvash, F, Mottaghi, T, Askari, G
Nutrition journal. 2020;19(1):101
-
-
-
-
Free full text
Plain language summary
Migraine is a chronic neurovascular disorder. Patients with this disorder suffer from severe headaches and also nausea, vomiting, photophobia, and phonophobia during a migraine attack. Several supplementary treatments have been suggested for the management of migraine symptoms. Among these methods, there is the supplementation with micronutrients. The aim of this study was to examine the effect of zinc supplementation on characteristics of migraine attacks in migraine patients. This study is a double-blind randomized clinical trial which included migraine patients, with an age range between 20 and 60 years. Patients were stratified based on age (20–40 and 40–60 years), gender (male and female), and body mass index (18.5–24.9 and 25–30) into different blocks. Then, they were randomly allocated to the intervention or control groups. Results show that when compared to the placebo group, zinc supplementation resulted in a significant reduction in headache severity and migraine attacks frequency. However, the effect on headache severity became statistically non-significant when baseline values of headache severity and potential confounders were taken into account. Authors conclude that zinc supplementation was beneficial for migraine attack frequency but not for migraine attack duration and headache daily results.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Inadequate zinc intake may drive migraine frequency.
- Zinc supplementation may enhance the effectiveness of routine migraine treatment in reducing migraine frequency.
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:
Migraines, characterised by severe headaches, nausea, vomiting, photophobia, and phonophobia affect approximately 10-20% of the global population. The authors refer to observational studies that have identified a moderate rate of zinc deficiency amongst migraine sufferers.
Zinc, an essential trace mineral, may prove beneficial as a supplement to reduce migraine symptoms and frequency possibly due to its effects on the nervous system and its antioxidant and anti-inflammatory capacity..
This double blind randomised clinical trial analysed the effects of 220mg of zinc sulphate (50mg of elemental zinc) combined with a routine migraine treatment versus a control group receiving a placebo and the routine treatment on symptoms of migraine attacks. The study duration was 8 weeks occurring from January 2016 to April 2016. Each group consisted of 40 participants between the ages of 20 and 60 with >5 years of migraines or migraine symptoms.
When compared to the placebo group, zinc supplementation demonstrated:
- A reduction in headache severity (− 1.75 ± 1.79 vs. -0.80 ± 1.57; P = 0.01). This result became statistically non-significant when the analysis was adjusted for potential confounders and baseline values of headache severity.
- A reduction in migraine attacks frequency (− 2.55 ± 4.32 vs. -0.42 ± 4.24; P = 0.02).
Clinical practice applications:
This randomised controlled trial highlights that zinc supplementation combined with routine migraine treatment (200/500 mg sodium valproate (such as Depakin), 50/100 mg sumatriptan, or 1 mg ergotamine) may assist in the reduction of migraine attack frequency amongst migraine sufferers within 8 weeks.
Compliance rate for this study was very high at 100% and there were no adverse effects reported suggesting a potentially safe and convenient treatment for migraine sufferers.
Considerations for future research:
- Further trials with better dietary controls would be useful to eliminate potential confounders.
- Use of CONSORT guidelines for reporting randomised trials would strengthen research reporting.
- Analysis of biomarkers may assist in identifying the mechanisms in which zinc may relieve migraine symptoms..
- Larger randomised controlled trials with increased sample sizes and longer durations are needed in order to definitively determine the effect of zinc supplementation on migraine attacks and any differences between genders.
- Additional studies trialling various zinc dosages and forms may provide insight into an optimal zinc dose and form for migraine attacks.
Abstract
BACKGROUND Observational studies have shown a link between zinc deficiency and migraine headaches. We aimed to examine the effect of zinc supplementation on the characteristics of migraine attacks in patients with migraine. METHODS This randomized clinical trial was conducted on 80 patients with migraine. Patients were randomly assigned to receive either zinc sulfate (220 mg/d zinc sulfate) or placebo (lactose) for 8 weeks. Anthropometric measures, serum zinc concentrations, and characteristics of migraine attacks (headache severity, frequency and duration of migraine attacks, and headache daily results) were assessed at baseline and end of the trial. RESULTS Compared with the placebo, zinc supplementation resulted in a significant reduction in headache severity (- 1.75 ± 1.79 vs. -0.80 ± 1.57; P = 0.01) and migraine attacks frequency (- 2.55 ± 4.32 vs. -0.42 ± 4.24; P = 0.02) in migraine patients. However, the observed reduction for headache severity became statistically non-significant when the analysis was adjusted for potential confounders and baseline values of headache severity. Other characteristics of migraine attacks including the duration of attacks and headache daily results were not altered following zinc supplementation either before or after controlling for covariates. CONCLUSION Zinc supplementation had a beneficial effect on the frequency of migraine attacks in migraine patients. Additional well-designed clinical trials with a long period of intervention and different dosages of zinc are required. TRIAL REGISTRATION CODE IRCT20121216011763N23 at www.irct.ir .
-
7.
Effect of 12-Week Daily Intake of the High-Lycopene Tomato (Solanum Lycopersicum), A Variety Named "PR-7", on Lipid Metabolism: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.
Nishimura, M, Tominaga, N, Ishikawa-Takano, Y, Maeda-Yamamoto, M, Nishihira, J
Nutrients. 2019;11(5)
-
-
-
-
Free full text
Plain language summary
Tomatoes are a rich source of lycopene, a compound believed to have many health benefits. Researchers in Japan conducted a randomised, double-blind, placebo-controlled trial to investigate the effects of eating a type of tomato bred to be high in lycopene on 74 healthy volunteers with raised cholesterol levels. Participants were given 50g per day of either semi-dried high-lycopene tomato or lycopene-free tomato. Those eating the high-lycopene tomatoes significantly reduced their levels of LDL cholesterol over 12 weeks. The researchers concluded that their findings support the health benefits of eating tomatoes rich in lycopene.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Lycopene, a carotenoid, has antioxidant effects and exhibits the highest physical quenching rate constant for singlet oxygen.
- Lycopene has also been reported to inhibit the production of serum lipid peroxide and oxidize low-density lipoprotein (LDL)
- This study reported that the intake of 50g of high-lycopene (lycopene, 22.0-27.8mg) for 12 weeks significantly decreased LDL-C in subjects with LDL-C ranging from 120–139 mg/dL.
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:
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group study was conducted to investigate the effects of the regular and continuous intake of high-lycopene tomato, a variety named PR-7, for 12 weeks on 74 healthy Japanese subjects with low-density lipoprotein cholesterol (LDL-C) levels > 120 to <160mg/dL.
The subjects were randomly assigned to either the high-lycopene tomato or placebo (lycopene-free tomato) group. Each subject in the high-lycopene group ingested 50g of semi-dried PR-7 (lycopene, 22.0-27.8mg) per day. Medical interviews were conducted, vital signs were monitored, and blood and saliva samples were taken at 0 (baseline) and at 4, 8 and 12 weeks.
Primary clinical outcomes were:
- The intake of high-lycopene tomato improved LDL-C at week 12 when compared to the placebo group (Week 12: placebo, 4,1 +- 15.7mg/dL; high-lycopene tomato, -3.7 +- 13.8.mg/dL; p=0.027).
- Based on a subgroup analysis, the ingestion of high-lycopene tomato significantly decreased LDL-C in subjects with LDL-C ranging from 120–139 mg/dL at week 12 (Week 12: placebo, 4.3 15.1 mg/dL; high-lycopene tomato, +- 5.1 9.5 mg/dL; p = 0.030).
Secondary clinical outcomes were:
- There were no significant differences between the high-lycopene tomato and placebo groups in terms of lipid profiles comprising of total cholesterol (TC), HDL-C, triglycerides (TG), LDL-C/HDL-C ratio, and non-HDL, and adiponectin.
- The intake of high-lycopene tomato increased lycopene levels compared to the placebo group (Week 12: placebo,
+-24.2 49.3 g/dL; high-lycopene tomato, 22.7 47.9 g/dL; p < 0.001).
- In addition, beta-carotene levels increased in the high-lycopene tomato group compared to those in the placebo group at week 12 (Week 12: placebo, 0.9 13.6 g/dL; high-lycopene tomato, 12.0 24.5 g/dL; p = 0.009).
Clinical practice applications:
- A previous meta-analysis demonstrated that LDL-C decreases when more than 25 mg per day of lycopene is ingested. The biological mechanism was associated with a reduction in 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase activity in the liver, activation of LDL-receptors, and increased expression of the ABCA1 transporter gene, the key component of HDL-C production.
- This study also suggests that there is a decrease in LDL-C at 12 weeks in subjects with LDL-C ranging from 120–139 mg/dL.
- Based on these findings, a practitioner could therefore consider recommending 25mg of lycopene to help reduce LDL-C in patients with an LDL-C range of 120–139 mg/dL for at least 12 weeks.
Considerations for future research:
- Lycopene has been reported to possess the strongest singlet oxygen scavenging ability among the eight carotenoids, as measured by the singlet oxygen absorption capacity method, and some researchers have found that lycopene and tomato display antioxidant effects. However, other reports suggest that ingesting lycopene does not affect oxidative markers. These findings suggest that further investigation is needed to evaluate the effect of lycopene on oxidative markers.
- The LOX index is a biomarker for the early risk of arteriosclerosis, cerebral infarction, and myocardial infarction. Lycopene might be ineffective against LOX-1 which is a product of the peroxidation reaction. Additional studies with a longer intake period are required to investigate the effect of lycopene on the risk of arteriosclerosis.
- The subjects in this study were asked to avoid cooking the test food (semi-dried tomato). It is, therefore, necessary to investigate the differences in the effect of the high-lycopene tomato based on various cooking methods.
Abstract
Tomato (Solanum lycopersicum) is a rich source of lycopene, a carotenoid that confers various positive biological effects such as improved lipid metabolism. Here, we conducted a randomized, double-blind, placebo-controlled, parallel-group comparative study to investigate the effects of regular and continuous intake of a new high-lycopene tomato, a variety named PR-7, for 12 weeks, based on 74 healthy Japanese subjects with low-density lipoprotein cholesterol (LDL-C) levels ≥120 to <160 mg/dL. The subjects were randomly assigned to either the high-lycopene tomato or placebo (lycopene-free tomato) group. Each subject in the high-lycopene group ingested 50 g of semidried PR-7 (lycopene, 22.0-27.8 mg/day) each day for 12 weeks, while subjects in the placebo group ingested placebo semidried tomato. Medical interviews were conducted, vital signs were monitored, body composition was determined, and blood and saliva samples were taken at weeks 0 (baseline), 4, 8, and 12. The primary outcome assessed was LDL-C. The intake of high-lycopene tomato increased lycopene levels in this group compared to levels in the placebo group (p < 0.001). In addition, high-lycopene tomato intake improved LDL-C (p = 0.027). The intake of high-lycopene tomato, PR-7, reduced LDL-C and was confirmed to be safe.