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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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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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Physical Training and Healthy Diet Improved Bowel Symptoms, Quality of Life, and Fatigue in Children With Inflammatory Bowel Disease.
Scheffers, LE, Vos, IK, Utens, EMWJ, Dieleman, GC, Walet, S, Escher, JC, van den Berg, LEM
Journal of pediatric gastroenterology and nutrition. 2023;77(2):214-221
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Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, are chronic inflammatory diseases of the gastrointestinal tract, characterised by periods of remission and relapse of symptoms. The aim of this study was to assess the effects of a tailored lifestyle intervention on physical fitness (maximal and submaximal exercise capacity, strength, and core stability), the patient-reported outcomes (quality of life, fatigue, and fear), clinical disease activity, and nutritional status. This study was a prospective single-centre randomised semi-crossover-controlled trial. Children were randomized into group A (start exercise) or group B (start control period). Results showed improved physical fitness, quality of life, and parent-reported fatigue. Additionally, a combination of lower clinical disease activity scores accompanied by fewer IBD symptoms suggests positive effects on intestinal inflammation. Authors concluded that based on the findings of their study, children and adolescents with IBD should be motivated and supported to acquire and maintain a healthy lifestyle.
Expert Review
Conflicts of interest:
None
Take Home Message:
- IBD is a chronic inflammatory disease of the gastrointestinal tract, characterised by periods of abdominal pain, severe diarrhoea, and fatigue
- This clinical trial suggests that a 12-week program of physical training plus personalised healthy dietary advice may improve physical fitness, quality of life, and fatigue in children with IBD.
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:
Introduction
A randomised semi-crossover controlled trial was conducted to investigate the impact of a 12-week lifestyle program (3 physical training sessions per week plus personalised healthy dietary advice) in children with Inflammatory Bowel Disease (IBD).
Method
- Sixteen children with a median age of 15 [IQR: 12–16]) that were diagnosed with IBD (CD, UC, or IBD-unclassified) were randomized to group A (start exercise) or group B (start control period). Group A started the intervention immediately after the first assessment and did not have a control period. Group B started after a control period (this was planned to last for 6 weeks but due to the COVID-19 lockdown extended to 6 months)
- The lifestyle intervention lasted 12 weeks and consisted of 3 physiotherapist-supervised training sessions per week, lasting 60 minutes each. In addition, all participants received a recommended caloric intake per day based on measured rest energy expenditure and a brochure regarding healthy diet in children
- Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (faecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition)
- A total of 15 out of 16 participants (93%) completed the program, one patient dropped out after one training session due to motivational problems.
Results
The primary findings of this study were as follows:
- While medical treatment remained unchanged, Paediatric Crohn's Disease Activity Index decreased versus the control period (15 [3–25] vs 2.5 [0–5], P = 0.012)
- The number of patients in clinical remission increased from 5 to 12 (P < 0.001), compared to the control period
- Quality of life (IMPACT-III) improved on 4 out of 6 domains and the total score (+13 points) versus the control period including a large improvement in bowel-related symptoms, P= 0.029)
- Fecal calprotectin decreased, but not compared to the control period, mainly due to relatively large intra-patient fluctuations (400 μg/g [57.1–1662.7] vs 128 μg/g [23.8–642.3], P = 0.016)
- Parents reported an improvement in the quality of life versus the control period on the child health questionnaire and total fatigue score (PedsQoL • Multidimensional Fatigue Scale) (+14 points, P = 0.048)
- Walking distance improved after the 12-week program, compared to the control period (P = 0.001).
Conclusion
This study revealed that a 12-week physical training program and personalised dietary advice improved bowel symptoms, quality of life, and fatigue in children with IBD.
Clinical practice applications:
- The mechanism behind the anti-inflammatory effects of exercise has not been clarified
- Multiple theories have been suggested in previously published studies such as a reduced release of adipokines due to less visceral fat, increased secretion of anti-inflammatory cytokines such as interleukin (IL)-6, and reduced transient stool time
- This clinical trial demonstrated that a 12-week program of physical training sessions plus personalised healthy dietary advice resulted in improved physical fitness, quality of life, and parent-reported fatigue.
Considerations for future research:
- A sample size calculation was not provided in the study report and it is therefore assumed that the sample size of 16 children in this trial was too small to draw a definite conclusion. A larger study over a longer period is therefore needed across diverse age and ethnic population groups to draw better conclusions
- This study did not measure mucosal inflammation before and after the intervention due to the invasive nature of the procedure. It would however be useful that future research investigate this to gain more insight into the effect of lifestyle interventions on IBD.
Abstract
OBJECTIVES Physical activity programs have been suggested as adjunctive therapy in adult inflammatory bowel disease (IBD) patients. We assessed the effects of a 12-week lifestyle intervention in children with IBD. METHODS This study was a randomized semi-crossover controlled trial, investigating a 12-week lifestyle program (3 physical training sessions per week plus personalized healthy dietary advice) in children with IBD. Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (fecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition). Change in maximal exercise capacity (peak VO 2 ) was the primary endpoint; all others were secondary endpoints. RESULTS Fifteen patients (median age 15 [IQR: 12-16]) completed the program. At baseline, peak VO 2 was reduced (median 73.3% [58.8-100.9] of predicted). After the 12-week program, compared to the control period, peak VO 2 did not change significantly; exercise capacity measured by 6-minute walking test and core-stability did. While medical treatment remained unchanged, Pediatric Crohn's Disease Activity Index decreased significantly versus the control period (15 [3-25] vs 2.5 [0-5], P = 0.012), and fecal calprotectin also decreased significantly but not versus the control period. Quality of life (IMPACT-III) improved on 4 out of 6 domains and total score (+13 points) versus the control period. Parents-reported quality of life on the child health questionnaire and total fatigue score (PedsQoL Multidimensional Fatigue Scale) also improved significantly versus the control period. CONCLUSIONS A 12-week lifestyle intervention improved bowel symptoms, quality of life, and fatigue in pediatric IBD patients.
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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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Adherence to a Mediterranean Diet for 6 Months Improves the Dietary Inflammatory Index in a Western Population: Results from the MedLey Study.
Clark, JS, Dyer, KA, Davis, CR, Shivappa, N, Hébert, JR, Woodman, R, Hodgson, JM, Murphy, KJ
Nutrients. 2023;15(2)
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Chronic inflammation is thought to be an underlying cause of many chronic diseases and diet can be used to modulate inflammation. The dietary inflammatory index (DII) is a tool rating an individual’s diet as pro- or anti-inflammatory, with an anti-inflammatory diet (low DII) being associated with a reduced risk of cardiometabolic disease. The aim of this 6-month randomised controlled trial was to evaluate the effect of a Mediterranean diet (MedD), as compared to a typical Australian diet (AusD), on DII and cardiometabolic risk factors in healthy Australians aged 65 years or older. Participants on the MedD significantly decreased their DII and had reductions in F2-Isoprostanes (marker of oxidative stress), triglycerides and systolic BP at 3 months and 6 months as well as improved endothelial function at 6 months. However, changes in DII did not correlate with changes in cardiometabolic risk factors. Evaluation of baseline parameters of both groups combined showed associations of DII with BMI, weight, abdominal fat, HDL and systolic blood pressure, with a lower DII correlating with lower risks. The authors concluded that a MedD decreases the DII which may help reduce the risk of cardiovascular disease.
Expert Review
Conflicts of interest:
None
Take Home Message:
- When individuals follow The Mediterranean Diet they are able to reduce their dietary inflammation score.
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
- Chronic inflammation is thought to be an underlying cause of many chronic diseases.
- The dietary inflammatory index (DII) is a tool for rating an individual’s diet as pro- or anti-inflammatory. A low DII (anti-inflammatory diet) is associated with reductions in cardiometabolic diseases.
- The aim of the study was to evaluate the effect of a dietary intervention (Mediterranean diet) on DII and cardiometabolic risk factors in older Australians.
Methods
- Randomised controlled trial.
- Duration: 6 months.
- Participants: 152 healthy Australian men and women aged 65 years or older.
- Intervention: Traditional Mediterranean diet (MedD, fortnightly sessions with dietician); control: Habitual Australian diet (AusD)
- Outcome measures: DII and energy-adjusted DII (E-DII), blood pressure (BP), anthropometric parameters, endothelial function (measured as flow mediated dilatation, FMD), F2-isoprostanes (F2-IsoP, marker of oxidative stress), inflammatory biomarkers, lipids, glucose, insulin, dietary compliance, cognitive performance.
Results
- Over the 4 months, the E-DII decreased by 1.1 points in the MedD group (<0.001), but did not decrease in the AusD group (p=0.21).
- Compared to AusD, participants on MedD had reductions in F2-IsoP, triglycerides and systolic BP at 3 months and 6 months; improved endothelial function at 6 months (no p-values given as reported elsewhere).
- No associations between changes in DII and changes in cardiometabolic outcomes, independent of whether participants were normal or overweight.
- Baseline E-DII scores of both groups combined were divided into tertiles and associations with cardiometabolic parameters evaluated (p-values refer to highest vs lowest tertile):
- Higher E-DII was associated with higher BMI (p=0.04); body weight (p<0.0001); hip-to-waist ratio (p=0.001) and abdominal fat (p=0.03).
- Lower E-DII was associated with higher HDL cholesterol (p=0.04) and lower systolic BP (p=0.005).
- No associations between E-DII and other outcome measures.
Conclusion
- The authors concluded that adherence to a MedD reduces dietary inflammation index scores, which may be beneficial for reducing chronic disease risk.
Clinical practice applications:
- The Mediterranean diet lowers dietary inflammatory index scores. This may, in turn, help reduce risk of cardiometabolic disease.
Considerations for future research:
- Larger and longer-term trials may confirm whether or not the reduction of DII with a MedD translates into a reduction in measurable inflammation and cardiovascular disease.
Abstract
Increasing evidence supports that a higher dietary inflammatory index (DII®) score is associated with inflammation and cardiovascular disease (CVD) risk, events, and mortality. This randomized trial sought to determine if a change to a Mediterranean diet resulted in a reduction in the DII score, and then it evaluated the relationship between the DII and cardiometabolic outcomes following the administration of a traditional Mediterranean diet in older Australian adults. A total of 152 Australian adults (mean age 71 ± 5 years) was randomly allocated either a MedDiet (n = 80) or to continue their habitual diet (HabDiet) (n = 72) for 6 months. Diet and cardiovascular outcomes were measured at baseline and 3 and 6 months of the intervention. DII and energy-adjusted DII (E-DIITM) scores were calculated from 3-day weighed food records. There was a significant reduction in the DII score at 2 and 4 months for the MedDiet group (−1.40 ± 0.20 p < 0.001 and −1.47 ± 0.20 p < 0.001, respectively), which was significantly different from the HabDiet group over time (p < 0.001). The HabDiet DII score did not change significantly at the 2 and 4 months timepoints (0.47 ± 0.21 p = 0.35 and 0.54 ± 0.21 p = 0.21, respectively). The improvement in the DII in the MedDiet group was not related to any cardiometabolic outcome. Baseline cross-sectional analyses identified a positive association between the E-DII score and average BMI, body weight, WHR, abdominal adiposity, and SBP, and a negative association with HDL-C. We demonstrate that a MedDiet intervention significantly reduced DII scores compared with a habitual Australian diet in older Australians. This could be beneficial for healthy ageing and the avoidance of chronic disease in Western populations.
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A Low-FODMAP Diet Provides Benefits for Functional Gastrointestinal Symptoms but Not for Improving Stool Consistency and Mucosal Inflammation in IBD: A Systematic Review and Meta-Analysis.
Peng, Z, Yi, J, Liu, X
Nutrients. 2022;14(10)
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The low-FODMAP diet eliminates carbohydrates that cannot be easily digested in order to reduce functional gastrointestinal symptoms associated with irritable bowel disease (IBD). The symptoms of irritable bowel disease include abdominal pain and bloating. This systematic review and meta-analysis aimed to evaluate whether a low-FODMAP diet can alleviate functional gastrointestinal symptoms in individuals with inflammatory bowel disease. In comparison with a regular diet, a low-FODMAP diet significantly reduced symptoms of bloating, wind, flatulence, abdominal pain, fatigue, and lethargy in patients with IBD. In addition, patients with Crohn's disease have achieved remission or reduced symptoms after following a low-FODMAP diet. Healthcare professionals can use this study to understand better the effects of a low-FODMAP diet on patients with IBD who have functional gastrointestinal symptoms. Further robust studies are, however, required to evaluate the evidence's robustness and identify the mechanism behind the improvement of symptoms.
Expert Review
Conflicts of interest:
None
Take Home Message:
- LFD use in IBD improved symptoms of bloating, wind or flatulence, borborygmi, abdominal pain, and fatigue or lethargy, but not nausea and vomiting.
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
This meta-analysis assesses the efficacy of a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet (LFD) in inflammatory bowel disease [IBD: ulcerative colitis (UC) and Crohn’s disease (UC)] participants with functional gastrointestinal symptoms (FGSs).
Methods
A search was performed on PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), WanFang (Chinese) Database up to March 2022. Quality assessment of all included studies was performed.
Results
9 studies (4 randomised controlled trials, 5 non-randomised studies) with a total of 351 participants diagnosed with IBD were included, and compared LFD with a placebo diet or normal diet (ND), overall and individual
LFD Effects of FGS:
- Overall 9 studies: an improvement (0.47, 0.33–0.66, p = 0.0000)
- No difference in the subgroup classified by disease type
- CD and UC: no improvement
Individual improvement:
- Bloating (0.37, 0,24-0,57, p=0.0000); wind or flatulence (0.38, 0,28-0,51, p=0.0000); borborygmi (0.48, 0,26-0,89, p=0.0000), abdominal pain (0.5, 0,37-0,68, p=0.0000), fatigue/lethargy (0.71, 0,61-0,82, p=0.0000)
- No difference in nausea and vomiting (0.54, 0,22-1,32, p=018)
IBS Quality of Life Score:
- 2 studies: reduced Short IBD Questionnaire (SIBDQ) score (11.24, 6.61-15.87, p=0.0000)
Bristol Stool Form Chart:
- 2 studies: normal stool consistency (type 3-4); no difference (5.99, 0.17-216.51, p=0.33)
- 2 other studies: no difference (-0.17, 0.48 - 0.15, p=0.30)
Diseases activity (Harvey-Bradshaw index):
- 2 studies using the Mayo score: no difference (-32, -1,09-0.45, p=0.41)
- 3 studies using BHi score: reduction (-1.09, -1,77-0.42, p=0.002)
Faecal calprotectin:
- 2 studies: no change (-16.03, -36,78-4.73, p=0.13)
Limitations
- Comparison diets were not standardised, suggesting the potential of different dietary habits to bias results..
- Heterogeneity of included studies, and the relatively small sample size of the studies can reduce the reliability of the results.
Conclusion
While the study found inconsistent definition standards for FGS, all the nine studies showed that LFD was associated with an improvement in some symptoms.
Clinical practice applications:
- This study suggests that IBD patients with FGSs may benefit from LFD treatment with the assistance of a healthcare professional.
Considerations for future research:
- This study has shown that LFD can improve FGSs in IBD, but further research with a larger sample size and more comprehensive analysis is warranted to replicate the results.
- The description of the findings and Quality of Life data are a little unclear. The impact on Quality of Life warrants further investigation, as clinicians need to consider the impact of following a restrictive diet on Quality of Life.
Abstract
BACKGROUND A low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet (LFD) is claimed to improve functional gastrointestinal symptoms (FGSs). However, the role of LFD in inflammatory bowel disease (IBD) patients with FGSs remains unclear. OBJECTIVE To systematically assess the efficacy of LFD in IBD patients with FGSs. METHODS Six databases were searched from inception to 1 January 2022. Data were synthesized as the relative risk of symptoms improvement and normal stool consistency, mean difference of Bristol Stool Form Scale (BSFS), Short IBD Questionnaire (SIBDQ), IBS Quality of Life (IBS-QoL), Harvey-Bradshaw index (HBi), Mayo score, and fecal calprotectin (FC). Risk of bias was assessed based on study types. A funnel plot and Egger's test were used to analyze publication bias. RESULTS This review screened and included nine eligible studies, including four randomized controlled trials (RCTs) and five before-after studies, involving a total of 446 participants (351 patients with LFD vs. 95 controls). LFD alleviated overall FGSs (RR: 0.47, 95% CI: 0.33-0.66, p = 0.0000) and obtained higher SIBDQ scores (MD = 11.24, 95% CI 6.61 to 15.87, p = 0.0000) and lower HBi score of Crohn's disease (MD = -1.09, 95% CI -1.77 to -0.42, p = 0.002). However, there were no statistically significant differences in normal stool consistency, BSFS, IBS-QoL, Mayo score of ulcerative colitis, and FC. No publication bias was found. CONCLUSIONS LFD provides a benefit in FGSs and QoL but not for improving stool consistency and mucosal inflammation in IBD patients. Further well-designed RCTs are needed to develop the optimal LFD strategy for IBD.
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6.
Igg Food Antibody Guided Elimination-Rotation Diet Was More Effective than FODMAP Diet and Control Diet in the Treatment of Women with Mixed IBS-Results from an Open Label Study.
Ostrowska, L, Wasiluk, D, Lieners, CFJ, Gałęcka, M, Bartnicka, A, Tveiten, D
Journal of clinical medicine. 2021;10(19)
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IBS, also known as irritable bowel syndrome, is a debilitating condition characterised by abdominal pain, irregular bowel movements, and changes in the consistency of stool. Symptoms of IBS may appear shortly after eating a meal. Excluding foods high in FODMAP carbohydrates, such as fermentable oligo- and di-saccharides, mono- and disaccharides, and polyols, or following an elimination rotation diet to reduce IgG-dependent food hypersensitivity, which has been shown to improve IBS symptoms previously. The purpose of this open-label study is to investigate the effectiveness of a low-FODMAPS diet and an elimination rotation diet based on IgG as well as a control diet in reducing symptoms of IBS. During the eight-week study, 73 female subjects with a mix of IBS were assigned to either of the three dietary treatments. Compared to the other diet groups, the IgG based elimination rotation diet group showed a significant improvement in the IBS symptoms and comorbid symptoms after the intervention period. In order to determine whether IgG-mediated food hypersensitivity plays a role in IBS and the efficacy of an IgG-dependent elimination rotation diet in the general population, further robust research is required. Healthcare professionals, however, can make use of these results to gain a better understanding of how an IgG based elimination diet tailored to each individual can improve IBS symptoms.
Expert Review
Conflicts of interest:
None
Take Home Message:
- After implementing the three diets, among patients with IBS-M, a statistically significant reduction of the frequency of the idiopathic abdominal pain, abdominal pain after a meal, abdominal pain during defecation, and sensation of incomplete defecation before and after the diet plans, were only found in Group 2.
- Significantly, only in the Group 2 IgG based elimination-rotation-diet was there a high decrease or complete disappearance of dyspeptic IBS symptoms and co-morbidities together with IBS symptoms.
- This study shows that a personalised dietary approach is more effective in treating IBS than generalised diet recommendations, with elimination diets focused on IgG antibodies providing the best results.
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:
Science supports the use of a low-FODMAP diet for symptom relief of IBS. However, more recently evidence suggests that IBS is a low-grade inflammatory disease that may result from or lead to IgG-dependent food hyper-sensitivities.
This study compared the effectiveness of three dietary treatment plans in 73 female patients diagnosed with mixed-form IBS based on Rome III criteria and no other gastrointestinal condition over 8 weeks.
The 3 dietary groups were:
- Group 1-low FODMAP diet
- Group 2- IgG based elimination-rotation-diet
- Group 3-control diet (control group)
Diets of G1 and G2 were determined individually by a dietitian, based on low-FODMAP dietary information and results from IgG food sensitivity testing respectively. Group 3 received nutrition advice from a gastroenterologist.
In G1, some of the IBS symptoms significantly improved (mucus in stool, p = 0.031; bloating, p < 0.001). Gurgling sensation and gastric fullness also reach statistical significance in G1.
IBS symptoms as well as co-morbid symptoms significantly improved or disappeared completely in G2 (idiopathic abdominal pain, p < 0.001; abdominal pain after a meal, p < 0.001; abdominal pain during defecation, p = 0.008; sensation of incomplete defecation p = 0.001; difficulty to defecate (constipation) p = 0.002; bloating p = < 0.001; gurgling sensation < 0.001; gastric fullness p = < 0.001. However, blood and mucus in the stool were impossible to test because the symptoms were not reported by any patient during the 2nd examination). (p-values less than 0.05 were considered statistically significant).
In group G3 no statistically significant improvements were seen in any measure.
Based on the results of this open-label study, it was concluded that personalised dietary interventions were more effective in the treatment of IBS-M patients than generalised diet recommendations. Dietary elimination based on IgG food sensitivity test results had the greatest impact on IBS and related symptoms.This study supports results from other studies showing an IgG-guided diet as an effective strategy in co-morbid conditions such as fatigue, headache/migraine, and skin conditions.
Conflicts of Interest
C.F.J.L., M.G. and A.B. are employees of the Institute of Microecology in Poznan ,where the ImuPro tests were determined. D.T. is the Head of Laboratory and shareholder of Lab1, offering ImuPro tests in Norway.
Clinical practice applications:
- Low FODMAP diets studies (NICE) showed GI improvements for abdominal pain, abdominal cramps, diarrhoea, gas, and bloating, largely because FODMAPs mainly cause an excessive production of gas, leading to discomfort and pain and an increased osmotic effect leading to increased bowel movement and diarrhoea. However 30% of patients still suffered from bloating on the FODMAP diet. Gurgling sensation decreased from 65% to 15%, and gastric fullness decreased from 58% to 11% in the patients on the low FODMAP diet.
- A potential new approach to resolve functional symptoms of gastrointestinal conditions could be to start with an IgG-guided elimination diet, as it was proven to be the more effective diet in this open study, and in cases of persistent symptoms, it could be combined with a low-FODMAP diet.
- Calprotectin is currently one of the best-known diagnostic markers indicating mucosa inflammation and changes in the inflammation intensity. In this study serious intestinal inflammation was diagnosed at the faecal calprotectin concentration of >50 mg/kg of stool. During the first examination, no statistically significant differences were found in calprotectin concentrations between the compared groups of patients, and the values were low, suggesting that the included patients suffered from low-grade inflammation and were suitable for diet alteration as the best choice of treatment.
Limitations:
- The main limitations of this study are the open-labeled nature, the low number of participants and the bias of only including female participants with only the patients in the G2 group tested for IgG food antibodies.
- Foods consumed by the patients before they entered the study were not ascertained.
Considerations for future research:
- Claims that IgG food antibodies only reveal exposure to food and not intolerance should be reinvestigated in larger double-blinded studies.
Abstract
Irritable bowel syndrome (IBS) is a chronic disease with recurrent abdominal pain, disturbed bowel emptying, and changes in stool consistency. We compared the effectiveness of three different dietary treatment plans (G1-FM-low FODMAP diet, G2-IP IgG based elimination-rotation-diet, and as control group, the G3-K control diet recommended by an attending gastroenterologist) in treating patients diagnosed with mixed irritable bowel syndrome. A total of seventy-three female patients diagnosed with a mixed form of irritable bowel syndrome (IBS-M) were enrolled in the study. The diet of each patient in Group 1 (G1-FM) and 2 (G2-IP) was determined individually during a meeting with a dietitian. Patients from Group 3 (G3-K) received nutrition advice from a gastroenterologist. Significant differences in the reduction of IBS symptoms were found between the groups. IBS symptoms as well as comorbid symptoms significantly improved or disappeared completely in the G2-IP group (idiopathic abdominal pain, p < 0.001; abdominal pain after a meal, p < 0.001; abdominal pain during defecation, p = 0.008), while in the G1-FM group, some of the IBS symptoms significantly improved (mucus in stool, p = 0.031; bloating, p < 0.001). In group G3-K no significant improvement was seen. Based on the results of this open-label study, it was concluded that various dietary interventions in the treatment of IBS-M patients do not uniformly affect the course and outcomes of disease management. Rotation diets based on IgG show significantly better results compared to other diets.
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7.
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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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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8.
Impact of Probiotics on the Performance of Endurance Athletes: A Systematic Review.
Díaz-Jiménez, J, Sánchez-Sánchez, E, Ordoñez, FJ, Rosety, I, Díaz, AJ, Rosety-Rodriguez, M, Rosety, MÁ, Brenes, F
International journal of environmental research and public health. 2021;18(21)
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The relationship between the gut microbiome and exercise has recently been explored to ascertain potential methods of improving athletic performance. Athletes have begun utilising probiotics to improve performance, support the immune system and reduce gastrointestinal problems, however no systematic review has been done to assess the efficacy behind these notions. The aim of this study is to review the use of probiotics in endurance athletes and assess both the direct and indirect associative factors. This review included nine studies and found improvements in athletic performance, oxidative stress markers, immune support, and incidence of upper respiratory tract infections with probiotic use. While there is little scientific evidence on the causative relationship between probiotics and performance, the authors conclude probiotics can enhance athletic performance by ameliorating the indirect consequences of oxidative stress and infection.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Endurance athletes may take probiotic supplements to support immune or GI health or for other reasons
- Currently there is little evidence that probiotics directly or specifically enhance athletic performance
- Probiotic supplementation potentially impacts on immune health particularly during intensive training and may facilitate muscle recovery or maintain performance
- Whilst probiotics may reduced GI symptom frequency and severity, further research is clearly warranted
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:
- There is current interest in the potential therapeutic benefits of probiotic strategies to support training and in-race performance for endurance athletes.
- Probiotic supplements are typically used by endurance athletes to limit or prevent upper respiratory tract infections (URTIs), reduce oxidative stress, support the immune system and modulate gastrointestinal function.
- Based on a limited number of articles sourced in this review (n=26), only 9 met the underlying quality and inclusion criteria. This highlights an important need for further research to be undertaken in this area.
- The review highlighted that different preparations, number of bacterial colony-forming units (CFUs), species type, timecourse and study objectives makes it difficult to determine fundamental conclusions on the efficacy of probiotics.
- That said, papers reviewed indicated the potential for a 55% increase in anti-inflammatory cytokines, reduced prevalence of URTIs, reduced Epstein-Barr and cytomegalovirus citrate antibodies, and improved recovery times.
- Probiotic supplementation likely enhances microbiota diversity and may indirectly support increased training load, and performance maintenance through immune defence. However, there were no indications that endurance performance was specifically enhanced.
Clinical practice applications:
- Most of the papers reviewed used formulae containing either Lactobacillus spp. (e.g. Plantarum, Acidophilus, Casei Shirota) or Bifidobacterium spp. (e.g. animalis subsp., bifidum, lactis, longum subsp.) or combinations. There was little mention of prebiotic or symbiotic strategies.
- Any impact of probiotics on exercise performance is likely to relate to both immune modulation and/or mechanisms leading to reduced muscle damage.
- Surprisingly, there was only partial mention of the use of probiotics for GI support and several notable papers were not included in the review. That said, the authors did note that with increased prevalence of exercise-induced gastrointestinal symptoms with endurance sport due to acute GI hypoperfusion and localised ischemia, acute probiotic strategies have resulted in reduced GI symptom frequency and severity in athletes.
- Importantly no adverse events following probiotic supplementation in endurance athletes were reported.
Considerations for future research:
- Clearly further research is warranted in terms of probiotic strain specific benefits both in training and in-race event effectiveness.
- The authors reported that there were no studies found on the effect of probiotics on hormonal or nervous systems in endurance athletes.
- Further research is needed to consider the impact of acute versus chronic probiotic use on intestinal metabolites, especially considering recent interactions between specific bacterial strains and short-chain fatty acid production being associated with performance (see: https://www.nutrition-evidence.com/article/31235964?term=31235964.
Abstract
BACKGROUND Probiotic supplements contain different strains of living microorganisms that promote the health of the host. These dietary supplements are increasingly being used by athletes to improve different aspects such as athletic performance, upper respiratory tract infections (URTIs), the immune system, oxidative stress, gastrointestinal (GI) problems, etc. This study aimed to identify the current evidence on the management of probiotics in endurance athletes and their relationship with sports performance. METHODS A systematic review of the last five years was carried out in PubMed, Scopus, Web of science, Sportdiscus and Embase databases. RESULTS Nine articles met the quality criteria. Of these, three reported direct benefits on sports performance. The remaining six articles found improvements in the reduction of oxidative stress, increased immune response and decreased incidence of URTIs. There is little scientific evidence on the direct relationship between the administration of probiotics in endurance athletes and sports performance. CONCLUSIONS Benefits were found that probiotics could indirectly influence sports performance by improving other parameters such as the immune system, response to URTIs and decreased oxidative stress, as well as the monitoring of scheduled workouts.
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9.
Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans.
Stekovic, S, Hofer, SJ, Tripolt, N, Aon, MA, Royer, P, Pein, L, Stadler, JT, Pendl, T, Prietl, B, Url, J, et al
Cell metabolism. 2019;30(3):462-476.e6
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Intermittent fasting and calorie restriction are believed to reduce cardiometabolic risk factors and increase longevity. Fasting alternate days (ADF) involves fasting for 36 hours and eating ad libitum for 12 hours. Thirty healthy participants were randomly assigned to a long-term ADF intervention group for ≥6 months against sixty participants in the control group. After completing the cross-sectional study arm, sixty healthy participants in the control group were randomly assigned to either a four-week short-term ADF intervention group or a control group with an ad libitum diet. Study participants adhered well to the fasting regimen. Both short-term and long-term ADF intervention groups showed a significant reduction in calorie intake, improvements in anthropometric and cardiovascular parameters including reduced BMI, substantial reduction in trunk fat, lower heart rate, increased serum β-hydroxybutyrate which is cardioprotective and anti-ageing, reduced circulating triiodothyronine (fT3) levels which indicate longevity. Short-term ADF reduced systolic and diastolic pressure, mean arterial pressure, pulse pressure, and pulse wave velocity. Long-term ADF intervention reduced circulating total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglycerides, the age-related biomarker sICAM-1 for disease and inflammation, and improved lipid and amino acid metabolites. ADF did not affect insulin sensitivity. Although red blood cells and iron levels were altered, ADF interventions were not associated with iron deficiency. Healthcare professionals can use the results of this study to understand the cardioprotective and anti-ageing properties of ADF. However, further long-term robust studies are required to evaluate the effect of long-term ADF on bone health.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Short duration (<4 weeks) alternate day fasting may be an effective way to implement caloric restriction, improve body composition and reduce cardiovascular disease risk in healthy non-overweight adults.
- >6 months alternate fasting does not appear to be associated with reduced bone mass, bone mineral density of the lumbar spine region, white blood cell counts, ferritin and transferrin when compared to healthy controls.
- Both short term and long term alternate day fasting may reduce triiodothyronine in healthy adults. Low levels of fT3 without thyroid gland dysfunction has been associated with longevity in humans.
- Alternate day fasting should be performed alongside a trained clinician to reduce the risk of adverse effects due to critical medical conditions.
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
Animal models have consistently demonstrated the healthspan and lifespan benefits of caloric restriction. However, chronic caloric restriction in humans has proven difficult to maintain.
Intermittent fasting may serve as a more manageable alternative to continuous caloric restriction. This randomised controlled trial and cross sectional analysis aimed to investigate the effects of alternate day fasting (ADF) on heart rate, blood pressure, cholesterol levels, CVD risk, body composition, and the metabolome and proteome of healthy, non-overweight adults (cohort median age between 48 and 52 years).
Methods
Prior to the enrollment of the study a cross sectional analysis was conducted on healthy adults engaged in long term (>6 months) alternate day fasting (n=30) and a control group (n=60).
The 60 participants from the cross sectional analysis control group were then randomised to either a 4 week ADF group or a control group. In both the >6 months and 4 weeks of ADF groups, participants were instructed to eat every second-day ad libitum, but to completely exclude solid and liquid foods and caloric beverages on fasting days.
Results
The cross sectional analysis identified that the alternate day fasting group:
- Consumed fewer calories vs the control group (−28.56%, p=0.0002).
- Had lower levels of circulating total cholesterol (p=0.004), LDL (p=0.011), VLDL (p=0.009), triglycerides (p=0.010) and a lower heart rate (p=0.040) vs the control group.
- Lower levels of soluble intercellular adhesion molecule-1 (sICAM-1) (p value 0.048), an age-associated inflammatory marker.
- Reduced circulating triiodothyronine (p<0.001) compared to the control group.
- In the metabolome, 54 out of 113 detected significantly modified metabolites (p value < 0.05) were at least 20% higher after 36 h of fasting, of which the majority (>95%) were lipids or free fatty acids, including polyunsaturated free fatty acids (PUFAs), α-tocopherol, and a type of vitamin E. 49 metabolites were at least 20% lower, consisting mainly (44.9%) of amino acids or related metabolites. Low levels of circulating amino acids have been found to increase lifespan in model organisms. The authors concluded that the elevation in fatty acids may be due to increased lipolysis from adipose tissue while the reduction in amino acids may be the result of increased gluconeogenesis.
- 13 out of 2,089 significantly (p value < 0.05) modulated protein hits within the PBMC proteome showed an increase of ≥15%, while the remaining proteins were downregulated after 36 h of fasting. Gene set enrichment analysis (GSEA) performed on the PBMC proteome unveiled changes in pathways related to lipid metabolism, pathways related to energy metabolism and stress response.
Following the 4 week intervention the alternate day fasting group demonstrated:
- Reduced caloric intake from baseline vs. the control group (−37.40% vs. −8.22%, p=0.0012).
- Greater reductions in body weight (−3.5kg vs −0.2kg, p<0.0001), BMI (−1.23kg/m2 vs −0.02kg/m2, p<0.0001) and improvements in their fat to lean mass ratio (−6.3% ± 5.0 percentage points, p value < 0.0001).
- Reduced systolic (−4.5mmHg, p=0.006) and diastolic (−2.5mmHg, p=0.03) blood pressure, heart rate (-4.5 b/min, p=0.0019), arterial (−3mmHg, p=0.0087) and pulse pressure (−2.5mmHg, p=0.0088) as well as pulse wave velocity (−1.538%, p=0.0362). Pulse wave velocity measures the rate at which pressure moves down the vessel wall and is a measure of arterial stiffness.
- Reduced circulating triiodothyronine (p<0.001) from baseline values.
Clinical practice applications:
The cross sectional analysis did not identify any differences in the long-term (>6 months) alternate day fasting group and control group in bone mass, bone mineral density of the lumbar spine region, white blood cell counts, ferritin and transferrin when compared to healthy controls. RBC counts and iron metabolism markers in the blood plasma (hematocrit, haemoglobin, iron, and transferrin saturation), were lower in the >6 months of ADF group but stayed within the reference range.
The randomised controlled trial demonstrated that alternate day fasting may be an effective intervention to reduce caloric intake, improve body composition and reduce cardiovascular disease risk in healthy non-overweight adults within 4 weeks.
Compliance rate was high with only 1 drop out in the alternate day fasting group of the randomised controlled trial.
Both the 4 week intervention and long-term (>6 month) analysis identified a reduction in triiodothyronine amongst the ADF groups. Low levels of triiodothyronine in absence of thyroid gland dysfunction has been associated with longevity in humans.
Considerations for future research:
- Future larger studies in non-healthy and/or overweight/obese populations would be useful to determine safety and efficacy of alternate day fasting within that population group.
- Further studies comparing alternate day fasting with continuous caloric restriction would be useful to identify which intervention is most beneficial for body composition and cardioprotection.
- Subgroup analysis of diet composition and diet quality may help to identify the most appropriate/inappropriate diet to compliment alternate day fasting.
- Longer duration randomised controlled trials are needed to identify any health risks or deficiencies which may develop with long term caloric restriction and alternate day fasting.
Abstract
Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after >6 months. ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-to-lean ratio, and increased β-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention.