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Polyphenol supplementation and executive functioning in overweight and obese adults at risk of cognitive impairment: A systematic review and meta-analysis.
Farag, S, Tsang, C, Murphy, PN
PloS one. 2023;18(5):e0286143
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It is recognised that overweight and obesity pose an increased risk for the development of cardiometabolic disease, and increasing evidence indicates a link to cognitive impairment associated with early onset dementia in such populations. This study's aim was to elaborate on existing knowledge of the effectiveness or otherwise of polyphenols in general to improve executive function (EFs) in an obese/ overweight population at risk of cognitive impairment. This study was a systematic review and meta-analysis of twenty-three randomised controlled trials. Results showed a nonsignificant effect of polyphenols on EFs. Authors concluded that further research should consider investigating polyphenols supplementation in a younger population at risk of cognitive impairment.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Overweight and obesity have increasing evidence that indicates a link to compromised executive functions such as memory and decision-making processes and cognitive impairment
- This meta-analysis revealed a non-significant effect of polyphenol supplementation on executive functions among overweight and/or obese populations with a susceptibility to cognitive impairment.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
A systematic review and meta-analysis were undertaken to investigate the impact of polyphenol supplementation on executive functions (cognitive functions which constitute part of the working memory and decision-making processes) among overweight and/or obese populations.
Method:
A comprehensive literature search was conducted using four electronic databases: PubMed/Medline, PsycInfo, Scopus and the Cochrane Trials Library. Inclusion criteria encompassed primary research studies which investigated the impact of polyphenols versus placebo on executive function in overweight or obese adults.
The review comprised a total of 23 randomised controlled trials (RCTs), incorporating a participant pool of N = 1,976 individuals. The mean ages of participants in all 23 studies receiving polyphenol supplementation were 62.92 years (SD = 8.06 years) and the mean BMIs ranged from 25.5 kg/m2 to 33.7 kg/m2. Various dietary polyphenols were investigated in the studies, with the main groups being isoflavones, flavonoids, resveratrol, phenolic acid, curcumin, walnuts and blueberry powder.
- The JADAD scale was employed to assess the methodological quality of the incorporated studies
- Hedges g, accompanied by 95% confidence intervals (CI) for endpoints, was computed utilising a random effects model whenever applicable
- Various statistical methods were considered for potential application in evaluating publication bias
- Sensitivity analysis was conducted to assess the robustness of the obtained results.
Results
- Meta analysis of the 23 primary studies produced a non-significant effect of polyphenol supplementation on executive function (g = 0.076, CI = -0.018 to 0.170)
- A double-blind, randomised, placebo-controlled parallel study reported significant benefits in 60 participants (mean age 67 years) taking 80mg of curcumin over placebo for digital vigilance and serial subtraction tasks (p=0.041)
- A double-blind, randomised, placebo-controlled parallel intervention trial showed significant benefits in 79 patients (mean age of 61 years) taking 150mg of resveratrol for visuospatial working memory double span and trail making test (p= 0.012).
Conclusion:
This meta-analysis revealed a non-significant effect of polyphenol supplementation on executive functions among overweight and/or obese populations.
Clinical practice applications:
- Research has documented the association between compromised executive functions and obesity/overweight, emphasising neuroinflammation and oxidative stress as potential mechanisms
- A plausible intervention involves the utilisation of polyphenols, known for their antioxidant and anti-inflammatory properties
- This systematic review and meta-analysis revealed a non-significant effect of polyphenol supplementation on executive functions
- A potential beneficial impact for 80mg of curcumin and 150mg of resveratrol was revealed in younger populations (mean ages of 67 and 61 years).
Considerations for future research:
- A potential beneficial impact of 80mg of curcumin and 150mg of resveratrol supplementation was revealed in a younger population (mean ages of 67 and 61 years), highlighting the necessity for in-depth exploration in subsequent studies
- The diversity in tasks employed for assessing executive functions and the comprehensive reporting of the phenolic composition of supplements had limitations that warrant consideration in future research
- The exact constituent and dose of supplementation needs to be described as this is necessary for the identification of the potential beneficial compounds for cognitive health and to support clinical practice.
Abstract
BACKGROUND AND OBJECTIVES Increasing evidence indicates a link between obesity and cognitive impairment. Furthermore, there is limited literature regarding the effect of polyphenols, a plant derived compounds, on executive functioning in an overweight/obese population at-risk of cognitive impairment. The aim of the present systematic review and meta-analysis of randomized controlled trials is to examine the effect of polyphenol supplementation on executive functions in overweight and/or obese populations at risk of cognitive impairment. METHODS A comprehensive literature search was conducted from inception to March 2023 using four electronic databases: PubMed/Medline, PsycInfo, Scopus and Cochrane trials library. Published primary research studies in English that compared the effect of polyphenols with placebo on executive function in overweight/obese adults were considered eligible for the meta-analysis. Jadad scale was used for the methodological quality rating of the included studies. Hedges g with 95% confidence intervals (CI) for endpoints were calculated using random effect model where applicable. Rosenthal's Fail-safe N, funnel plots, the Begg and Mazumdar's rank correlation test (Kendall's S statistic P-Q), Egger's linear regression test, and Duval and Tweedie's trim-and-fill test were identified for potential use as appropriate, to examine publication bias. Sensitivity analysis was conducted to examine the robustness of the results. RESULTS AND CONCLUSION A total of 23 RCT studies involving N = 1,976 participants were included in the review. The results of the meta-analysis revealed a non-significant effect for polyphenol supplementation on executive function (g = 0.076, CI = -0.018 to 0.170). Observations from primary studies within the meta-analysis showed a potential positive effect of polyphenol supplementation in a younger population at-risk of cognitive impairment and it is recommended to investigate this further in future studies. Moreover, the variability of the tasks used to examine executive functions as well as the adequate reporting of supplement's phenolic composition is a limitation that future work should also consider.
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2.
The effects of time-restricted eating on sleep, cognitive decline, and Alzheimer's disease.
Ezzati, A, Pak, VM
Experimental gerontology. 2023;171:112033
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The ageing population is expected to double, with one in four people being over 65 years in Western countries by 2050. As a consequence, the presentation of age-related disorders like Alzheimer's disease (AD) and mild cognitive impairment (MCI) is likely to increase. MCI, a pre-stage of dementia, is considered reversible. However, there are no known cures for AD so far. Hence interventions such as lifestyle modifications that can delay the onset and progression of the disease are of great interest. Previous research demonstrated that calorie restriction (CR) and time-restricted eating (TRE) have beneficial effects on brain function. The authors of this article sought to summarize the current evidence of such eating patterns, as well as their underlying mechanisms and potential benefits concerning MCI and AD. The review also looked at sleep - as sleep disturbances are a risk factor and are associated with both conditions - and the effects of sleep on cognitive decline and neuroinflammatory markers. TRE presents itself as a promising intervention as it can restore the integrity of the blood-brain barrier and support healthy brain function whilst reducing oxidative stress and inflammation. Furthermore, it can be leveraged for weight and glucose management. Preliminary results also indicate a positive impact on sleep, with adequate sleep benefiting cognitive health. As this is a relatively new field, there is still much more to be understood about the underlying mechanisms, with the optimal time window for fasting needing to be determined. The authors advocate for more research on how TRE and sleep relates to neurodegenerative disease.
Expert Review
Conflicts of interest:
None
Take Home Message:
- To highlight the potential benefits of time-restricted eating (TRE) as a potential preventative approach to delay the onset and progression of neurodegenerative disease such as AD
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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X
C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- The authors highlight Alzheimer's disease (AD) is the most prevalent neurodegenerative disease affecting over 50 million aging people worldwide. While no cure is known for AD, this review proposes lifestyle interventions such as time-restricted eating (TRE) as a potential approach to delay the onset and progression of a neurodegenerative disease and could hint at autophagic mechanisms
- TRE involves strategically limiting the eating window to 8- to 12-h with fasting—drinking only water and calorie-free coffee/tea—for 12 to 16 h within a 24-h cycle.
Objectives
- To investigate the effects of TRE on sleep and cognitive decline in healthy individuals
Results
- Nine RCTs with varied length between one and sixteen weeks were examined
- A 5-week randomised controlled trial (RCT) showed no significant change in sleep quality between early TRE (fasting between 6 a.m.–3 p.m.), mid-day TRE (11 a.m.–8 p. m.) and control (ad lib intake) in 82 healthy subjects without obesity but the sleep quality improvement was greater in early TRE group (PSQI:Δ=−1.08±1.78vs.Δ=−0.22±2.19andΔ=−0.36±1.73, respectively).
- Sleep quality using the myCircadianClock app reported significant improvement in sleep quality (23 %) following a 12-week single arm intervention of 10-h TRE.
- Following a 16-week TRE intervention sleep duration was reported to be improved from a subjective score of 6 at base line to 8 after 36 weeks in eight overweight and obese subjects; however, the study used a subjective self-assessment survey for measuring sleep duration.
- The Pittsburgh Sleep Quality Index (PSQI) was carried out to assess sleep quality and disturbances in six trials but no trial reported significant improvement in sleep quality using the PSQI survey with TRE
Conclusion
- Authors highlight TRE as promising for its potential to reduce the markers of aging and neurodegenerative disease.
Clinical practice applications:
- To inform practitioners of the potential benefits of TRE that involves limiting the eating window to 8- to 12-h with fasting—drinking only water and calorie-free coffee/tea—for 12 to 16 h within a 24-h cycle.
- TRE may improve regulation of circadian rhythm and autophagy through aligning food intake with circadian rhythm, which coordinates metabolism and physiological functions including glucose, insulin sensitivity, lipid levels, energy expenditure, inflammation, sleep and cognitive function.
- TRE activates a metabolic switch which occurs 12–36 h after fasting is initiated and free fatty acids are released into the blood.
- TRE improved sleep quality and sleep duration, where a longer fasting period in TRE approach (≥12 h fasting) was associated with significantly higher sleep duration.
Considerations for future research:
- The potential benefits of TRE in neurodegenerative diseases such as AD should be further investigated clinically.
- The optimal time to initiate fasting needs to be identified in future trials.
- The potential benefits of TRE in neurodegenerative diseases such as AD in the context of sleep should be further investigated.
Abstract
According to the United Nations, by 2050, one in six individuals will be over age 65 globally, and one in four people would be aged 65 and older in western countries. The unprecedented growth of the aging population is associated with increased age-related disorders like Alzheimer's disease (AD) and Mild cognitive impairment (MCI). To date, no cure is known for AD, thus lifestyle interventions including calorie restriction (CR) and time-restricted eating (TRE) are proposed as potential approach to delay the onset and progression of the disease. Sleep disturbances are common in people with MCI and AD. Moreover, accumulating data indicates that pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8 and IL-10 increase in individuals with AD and MCI versus healthy subjects. Thus, the purpose of the present review is to describe the potential effects of TRE on sleep, cognition decline, and neuroinflammatory markers in humans. Preliminary evidence suggests that TRE may produce neuroprotective effects on cognition and reduce neuroinflammatory markers related to AD in humans. To date, no studies investigated the effects of TRE on sleep disturbances and patients with AD. Thereby, the impact of TRE on cognition in individuals with cognitive decline and AD needs to be investigated further in randomized controlled trials (RCTs).
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3.
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
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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:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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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.
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4.
Effectiveness of Exercise Training on Male Factor Infertility: A Systematic Review and Network Meta-analysis.
Hajizadeh Maleki, B, Tartibian, B, Chehrazi, M
Sports health. 2022;14(4):508-517
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Male factor infertility is characterised by the existence of suboptimal sperm parameters in the male partner of childbearing age and is presently defined as the inability to conceive a child with frequent and unprotected sexual intercourse in the fertile phase of the menstrual cycles for a year or longer. The main aim of this study was to evaluate the effectiveness of 1 or more of the selected types of exercise interventions (moderate-intensity continuous training (MICT), resistance training (RT), combined aerobic and resistance training (CET), high-intensity continuous training (HICT), and high-intensity interval training (HIIT)) in the prevention and treatment of male factor infertility. This study is a systematic review and meta-analysis of seven randomised controlled trials representing 18 groups (11 exercise, 7 non-intervention control [NON-EX]) and 2641 participants and/or patients (1429 exercise, 1212 NON-EX). Results show that in the setting of couples with male factor infertility, when compared with the NON-EX group, selected types of exercise interventions improved the relative risk of pregnancy rate in the following order: CET > MICT > RT > HICT > HIIT. The top-ranking interventions for live birth rate were for MICT, RT, HIIT, CET, and HICT. In addition, the interventions with the highest probability of being the best approach out of all available options in improving semen quality parameters were for CET, MICT, HICT, RT, and HIIT. Authors conclude that when clinicians are formulating clinical recommendations for preventing and treating male factor infertility, the findings of this study should be considered.
Expert Review
Conflicts of interest:
None
Take Home Message:
- For couples with male factor infertility, this review recommends moderate intensity-aerobic exercise in combination with strength training to be the intervention with the highest probability of being the best approach for reproductive health benefits.
- A conservative interpretation of the findings is required because they were based on single studies.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
The World Health Organisation estimates that infertility affects 10% to 15% of couples in industrialised countries. Approximately 50% of all infertility cases are attributed to male-related factors, in particular, poor semen quality (called male factor infertility). The aim of this study was to evaluate the effectiveness of exercise training on male factor infertility and seminal markers of inflammation.
Methods
This is the first study to undertake a systematic review with network meta-analysis of 7 RCTs to evaluate the effectiveness of 1 or more types of exercise interventions on male factor infertility and seminal markers of inflammation, as well as to provide clinicians with a ranking of treatments to inform them of the treatment effects of exercise training and physical activity.
The forms of exercise include: moderate-intensity continuous training (MICT), resistance training (RT), combined aerobic and resistance training (CET), high-intensity continuous training (HICT), and high-intensity interval training (HIIT).
7 RCTs representing 18 groups (11 exercise (supervised, not home-based), 7 non-intervention control [NON-EX]) and 2641 participants and/or patients (1429 exercise, 1212 NON-EX). All the RCTs were conducted in Iran involving healthy adult participants and/or infertile patients (with doctor-diagnosed male factor infertility). The intervention period was ≥10 weeks with a follow-up period.
None of the studies reported changes in either patients’ dietary intakes or normal daily physical activities and lifestyles during the intervention period.
Results
Compared with a non-intervention control group, the top ranking interventions:
For pregnancy rate:
Combined aerobic and resistance training (CET) (p= 0.89 relative risk [RR] = 27.81), moderate-intensity continuous training (MICT) (p=0.87, RR = 26.67), resistance training (RT) (p=0.61,RR = 12.54), high intensity continuous training (HICT) (p=0.34, RR = 5.55), and high-intensity interval training (HIIT) (p=0.28, RR = 4.63).
For live birth rate:
MICT (p=0.82, RR = 10.05), RT (p=0.70, RR = 4.92), HIIT (p=0.66, RR = 4.38)), CET (p=0.45, RR = 2.20), and HICT (p=0.30, RR = 1.55)
The following parameters/markers rank the 5 exercise strategies in order of effectiveness:
- Semen quality parameters were significantly improved after the following types of exercise interventions as compared with the non-intervention group [NON-EX]: CET > MICT > HICT > RT > HIIT
- The following training strategies were significantly better at improving seminal markers of oxidative stress: CET > MICT > HIIT > HICT > RT
- The following training strategies were significantly better at improving seminal markers of inflammation: CET > MICT > HIIT > RT > HICT
- The following training strategies were significantly better at improving measures of body composition and VO2 max: CET > HICT > MICT > HIIT > RT
- There was insufficient evidence of a difference for the selected types of exercise interventions versus NON-EX group for pregnancy and live birth rates in healthy participants.
Conclusion
Combined aerobic and resistance training (CET) was found to be the intervention with the highest probability of being the best approach for improving the male factor infertility.
Clinical practice applications:
- In light of these findings, it is reasonable to propose that infertile men and at-risk populations take part in the top-ranking interventions identified in this analysis.
- For substantial reproductive health benefits, one should consider doing all of the selected types of exercise interventions (CET, MICT, RT, HICT, and HIIT); however, moderate intensity-aerobic exercise and strength training in combination would generally be more favourable to lend clinically significant improvements.
- To add to this, exercise can offer a myriad of other health benefits, is a possibly safe activity and a cost-effective treatment strategy for male factor infertility.
Considerations for future research:
- There was only a small number of relevant trials available for comparison suggesting the need for additional study in this field.
- Further trials are needed to analyse the dose-response impacts of exercise modalities on male reproductive function.
- The results propose several domains for development in the reporting of RCTs addressing the impacts of interventional exercise studies on male reproductive function.
- Heterogeneity of some findings and discrepancy across the included studies was significant. For example, variations in the characteristics of training programs. Future analyses should aim to continue to address this.
- There is a concern that this study may not relate to already active patients with male factor infertility which future studies should address.
Abstract
CONTEXT Mounting evidence from the literature suggests that different types of training interventions can be successful at improving several aspects of male reproductive function in both fertile and infertile populations. OBJECTIVE The aim of this study was to evaluate the effectiveness of exercise training on male factor infertility and seminal markers of inflammation. DATA SOURCES We searched PubMed, CISCOM, Springer, Elsevier Science, Cochrane Central Register of Controlled Trials, Scopus, PEDro, Ovid (Medline, EMBASE, PsycINFO), Sport Discus, Orbis, CINAHL, Web of Science, ProQuest, and the ClinicalTrials.gov registry for randomized controlled trials (RCTs) that analyzed the impacts of selected types of exercise interventions on markers of male reproductive function and reproductive performance. STUDY SELECTION A total of 336 records were identified, of which we included 7 trials reporting on 2641 fertile and infertile men in the systematic review and network meta-analysis. LEVEL OF EVIDENCE Level 1 (because this is a systematic review of RCTs). DATA EXTRACTION The data included the study design, participant characteristics, inclusion and exclusion, intervention characteristics, outcome measures, and the main results of the study. RESULTS The results of network meta-analysis showed that, compared with a nonintervention control group, the top-ranking interventions for pregnancy rate were for combined aerobic and resistance training (CET) (relative risk [RR] = 27.81), moderate-intensity continuous training (MICT) (RR = 26.67), resistance training (RT) (RR = 12.54), high-intensity continuous training (HICT) (RR = 5.55), and high-intensity interval training (HIIT) (RR = 4.63). While the top-ranking interventions for live birth rate were for MICT (RR = 10.05), RT (RR = 4.92), HIIT (RR = 4.38), CET (RR = 2.20), and HICT (RR = 1.55). Also, with the following order of effectiveness, 5 training strategies were significantly better at improving semen quality parameters (CET > MICT > HICT > RT > HIIT), seminal markers of oxidative stress (CET > MICT > HIIT > HICT > RT), seminal markers of inflammation (CET > MICT > HIIT > RT > HICT), as well as measures of body composition and VO2max (CET > HICT > MICT > HIIT > RT). CONCLUSION The review recommends that the intervention with the highest probability of being the best approach out of all available options for improving the male factor infertility was for CET.
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5.
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
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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:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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X
C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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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.
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6.
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
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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:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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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.
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7.
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
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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:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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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 .
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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)
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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:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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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.