-
1.
Impact of probiotics on muscle mass, muscle strength and lean mass: a systematic review and meta-analysis of randomized controlled trials.
Prokopidis, K, Giannos, P, Kirwan, R, Ispoglou, T, Galli, F, Witard, OC, Triantafyllidis, KK, Kechagias, KS, Morwani-Mangnani, J, Ticinesi, A, et al
Journal of cachexia, sarcopenia and muscle. 2023;14(1):30-44
-
-
-
-
Free full text
-
Plain language summary
Sarcopenia is a progressive skeletal muscle disorder involving accelerated loss of muscle mass, strength and function. It generally occurs in older age groups but can also be seen in younger people. Multiple factors contribute to the development of the condition. Besides nutritional management strategies, probiotics have recently caught the interest of researchers. As probiotics promote metabolic building activity, aid digestion and absorption and reduce muscle breakdown by favourably managing inflammation, they present great potential for the management of sarcopenia. This systematic review and meta-analysis explored the impact of probiotic supplementation on muscle mass, total lean mass and muscle strength in human adults. The review included 24 studies, with probiotics mainly from the Bifidobacteria or Lactobacilli family. The analysis concluded that probiotic supplementation improved muscle mass in comparison to placebos. It also significantly increased overall muscle strength in 6 randomized controlled trials, which was most obvious in age groups of 50 and above. However, no changes were seen concerning total lean mass. It appeared that longer studies, of >12 weeks or more, showed better outcomes in this review. Furthermore, Bifidobacteria species seemed to exhibit more favourable effects, and the authors also noted the beneficial results were more significant in Asian populations. Further research is needed to understand more about the underlying mechanism, best probiotics strains and the specifics of different demographic groups. This article yields a concise overview of sarcopenia, the nutritional aspects of the disease and how probiotics may be beneficial in disease management, strengthened with data from the review.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This was a well-conducted meta-analysis based on its methodological approach that demonstrated that Lactobacillus and Bifidobacterium probiotic supplementation may contribute to improved muscle mass in younger adults and improved muscle strength in older adults.
- Bifidobacterium probiotic supplementation was associated with enhanced muscle mass in younger adults, a potential focus for those considering probiotic supplements.
- The duration of probiotic therapy matters, with longer-term (12 weeks or more) supplementation showing improvements in muscle mass and strength..
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
This systematic review and meta-analysis evaluated the effect of probiotics on muscle mass, total lean mass and muscle strength in both young and older adults.
Methods
- The search encompassed PubMed, Scopus, Web of Science, and Cochrane Library databases, from inception up to June 2022; studies included spanned a period from 2013 to June 2022.
- The study adhered to Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines and included the Risk-of-Bias tool to assess study quality.
- The study focused on changes in muscle mass, total lean mass, and muscle strength.
- Inclusion criteria: randomised controlled trials (RCTs) with adult participants (>18 years); interventions involving any probiotics, and a control group receiving either no treatment or a placebo.
Results
- 24 RCTs were included (709 participants), with studies conducted in Europe, USA, and Asia. Intervention durations: ranged from 3 weeks to 12 months.
- Participants included overweight, untrained healthy and resistance-trained individuals, and those with specific conditions like metabolic syndrome and frailty.
- Body composition assessments were conducted using bioelectrical impedance (BIA) and/or dual-energy X-ray absorptiometry (DXA).
- Probiotic strains employed in the included studies varied, with Lactobacillus the most common, followed by Bifidobacterium; some combined both. 5 of 24 studies also used additional strains.
- Dosages: ranged from 2 × 10^9 to 11.2 × 10^10 colony-forming units (CFU).
- 4 out of 24 studies used fermented food products like cheese and noodles as sources of probiotics.
- 22 RCTs measured muscle mass and total lean mass; 6 RCTs measured global muscle strength.
- Probiotic supplementation (≥12 weeks) moderately increased muscle mass, with a standardised mean difference (SMD) of 0.42. This significant effect (95% CI: 0.10–0.74, P=0.009) was observed only in younger Asian adults (<50 years) after Bifidobacterium supplementation, based on a meta-analysis of 10 studies.
- Probiotic supplementation (≥12 weeks) significantly increased global muscle strength in older adults (>50 years; SMD: 0.69, 95% CI: 0.33–1.06, P = 0.0002).
- Probiotic supplementation showed no significant impact on lean mass (SMD: -0.03, 95% CI: 0.19 – 0.13, P = 0.69).
Conclusion
Probiotic supplementation, especially Lactobacillus and Bifidobacterium may have a positive impact on muscle mass and global strength
Clinical practice applications:
- Consumption of probiotics, mainly Lactobacillus and Bifidobacterium may contribute to improved muscle strength in older individuals (>50y).
- Consumption of Bifidobacterium strains was associated with improved muscle mass in younger individuals (<50y) in Asian countries, in a low number of studies (k=2).
- Bifidobacterium breve B-3 was associated with an improvement in muscle mass in older overweight individuals, although a causal relationship was not established.
- Probiotics may enhance muscle mass or strength by enhancing protein digestion and amino acid absorption for muscle synthesis and function.
- Considering an individual’s goals, a practitioner could consider probiotic supplementation as a complementary intervention when aiming to enhance muscle mass or strength .
Considerations for future research:
- Future research could focus on pinpointing which specific probiotic strains are most effective for muscle strength or muscle mass to tailor more precise interventions.
- Most studies did not exceed 12 weeks, highlighting the need for long-term research on probiotics sustained muscle impact.
- Future research could investigate the effects of probiotics across diverse demographic groups including different ages, sexes, and ethnic backgrounds to understand the impact in different populations.
- Delving deeper into the mechanisms by which probiotics influence muscle health could lead to targeted probiotic therapies that address specific physiological pathways.
- Finally, future research could explore how probiotics can be combined with other interventions, such as exercise or nutritional modifications, to synergistically improve muscle health and function.
Abstract
Probiotics have shown potential to counteract sarcopenia, although the extent to which they can influence domains of sarcopenia such as muscle mass and strength in humans is unclear. The aim of this systematic review and meta-analysis was to explore the impact of probiotic supplementation on muscle mass, total lean mass and muscle strength in human adults. A literature search of randomized controlled trials (RCTs) was conducted through PubMed, Scopus, Web of Science and Cochrane Library from inception until June 2022. Eligible RCTs compared the effect of probiotic supplementation versus placebo on muscle and total lean mass and global muscle strength (composite score of all muscle strength outcomes) in adults (>18 years). To evaluate the differences between groups, a meta-analysis was conducted using the random effects inverse-variance model by utilizing standardized mean differences. Twenty-four studies were included in the systematic review and meta-analysis exploring the effects of probiotics on muscle mass, total lean mass and global muscle strength. Our main analysis (k = 10) revealed that muscle mass was improved following probiotics compared with placebo (SMD: 0.42, 95% CI: 0.10-0.74, I2 = 57%, P = 0.009), although no changes were revealed in relation to total lean mass (k = 12; SMD: -0.03, 95% CI: -0.19 - 0.13, I2 = 0%, P = 0.69). Interestingly, a significant increase in global muscle strength was also observed among six RCTs (SMD: 0.69, 95% CI: 0.33-1.06, I2 = 64%, P = 0.0002). Probiotic supplementation enhances both muscle mass and global muscle strength; however, no beneficial effects were observed in total lean mass. Investigating the physiological mechanisms underpinning different ageing groups and elucidating appropriate probiotic strains for optimal gains in muscle mass and strength are warranted.
-
2.
Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.
Xia, J, Yu, J, Xu, H, Zhou, Y, Li, H, Yin, S, Xu, D, Wang, Y, Xia, H, Liao, W, et al
Pharmacological research. 2023;188:106647
-
-
-
-
Free full text
-
Plain language summary
Type 2 diabetes mellitus (T2DM), characterised by sustained hyperglycaemia and insulin resistance, remains a severe driver of chronic metabolic diseases such as cardiovascular diseases. The aim of this study was to investigate and compare the efficacy of vitamin and mineral supplements in the management of glycaemic control and lipid metabolism for type 2 diabetic patients to inform clinical practice. This study is a systematic review and meta-analysis of one hundred and seventy articles with a total of 4223 adults with T2DM. Participants were randomised to either the placebo/no treatment group (n= 6345) or to the treatment group (n= 7878). Results show that: - chromium was the most effective micronutrient for decreasing fasting blood glucose and insulin resistance. - vitamin K was the top-ranked micronutrient in reducing haemoglobin A1C and fasting insulin levels. - vanadium was the top-ranked micronutrient in total cholesterol reductions. - niacin was ranked as the most effective in triglycerides reductions and increasing high-density lipoprotein cholesterol levels. - vitamin E was the top-ranked micronutrient in low-density lipoprotein cholesterol reductions. Authors conclude that micronutrient supplements especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more effective in the management of T2DM compared with other micronutrients.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Clinicians could consider the adjunctive effect of micronutrients supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements in a nutrition protocol to manage T2DM and slow or prevent its complications.
- The study authors state that the vitamin and mineral supplements under review had a statistically significant improvement, however they did not reach the study threshold for clinical significance. Therefore they advise caution in utilising micronutrient supplements in the management of glucose and lipid metabolism for T2DM.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Objectives
The aim of this systematic review was to evaluate the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM).
Methodology
This systematic review is registered with PROSPERO and adhered to PRISMA-2020 guidelines for network meta-analysis
The Cochrane Collaboration’s risk-of-bias tool was used to assess eligible randomised trials
8 prespecified markers identified and assessed in this study : 1) HbA1c (%), 2) fasting blood glucose (mmol/L), 3) total cholesterol (mmol/L), 4) triglycerides (mmol/L), 5) fasting insulin (μIU/mL), 6) HOMA-IR, 7) LDL-c (mmol/L), and 8) HDL-c (mmol/L).
Results
- 170 RCT trials of 14223 participants with T2DM treated with vitamin supplements, mineral supplements, or placebo/no treatment were included
- Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively)
- Vitamin K supplements ranked best in reducing glycated haemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence
- Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%)
- Niacin supplements ranked best in triglyceride reductions and increasing high-density lipo-protein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively)
- Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%).
Conclusion
- Micronutrient supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be efficacious in managing T2DM
- It should be noted that the evidence certainty for all was low.
Clinical practice applications:
- Chromium plays an important role in carbohydrate and lipid metabolism and was the most effective micronutrient for decreasing fasting blood glucose, HbA1c, fasting insulin, and HOMA-IR reductions. More pronounced effects were seen for chromium than vitamin E, vitamin C, niacin, selenium, and magnesium supplements
- Vitamin K was the top-ranked micronutrient in reducing HbA1c and fasting insulin levels. The mechanism through which Vitamin K affects glucose metabolism is proposed as activation of the AMP-activated protein kinase/sirtuin 1, that in turn increases phosphocreatine 3-kinase and glucose transporter 2 to decrease insulin resistance and fasting glucose.
- Vanadium was the top-ranked micronutrient in total cholesterol (TC) reductions, where supplementation dosage should be carefully considered, as vanadium compounds can be moderately or highly toxic. Vanadium supplementation is only recommended in cases of vanadium deficiency or diabetes, hyperlipidemia, and hypertension, where the intake of vanadium from food should be enhanced in preference to supplementation
- Niacin was ranked as the most effective in triglyceride (TG) reductions and increasing HDL cholesterol levels. The dose of niacin could not be determined
- Vitamin E was the top-ranked micronutrient in low-density lipo- protein (LDL) cholesterol reductions.
Considerations for future research:
- Considering the clinical importance of these findings, new research is needed to get better insight into the efficacy of micronutrient supplements in managing T2DM
- Selenium homeostasis, selenoprotein, insulin signaling/secretion, and carbohydrate/lipid metabolism are linked in multiple and complex ways but the authors could not explain why chromium supplementation would lower blood glucose more effectively than selenium supplementation, and suggest more research is needed to clarify this
- While vitamin K status could be an emerging treatment target in T2DM prevention and management, it remains to be determined whether vitamin K supplementation has an advantage over other nutrients in terms of hypoglycemic effect, and further research is necessary
- The beneficial effect of vitamin E and niacin supplements regarding lipid metabolism warrant investigation through more rigorous comparative studies.
Abstract
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
-
3.
Distribution of energy intake across the day and weight loss: A systematic review and meta-analysis.
Young, IE, Poobalan, A, Steinbeck, K, O'Connor, HT, Parker, HM
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2023;24(3):e13537
-
-
-
-
Free full text
-
Plain language summary
Obesity increases an individual's risk of metabolic disease, such as diabetes and cardiovascular disease, musculoskeletal disorders such as osteoarthritis, and some cancers. “Chrononutrition” relates to the timing of meals and distribution of total energy intake across the day. Evidence is building chrononutrition as a potential target in both weight loss and metabolic disease interventions. The aim of this study was to examine the impact of earlier versus later distribution of total daily energy intake on weight loss, and to evaluate the potential for utilizing altered energy distribution as a tool in weight loss interventions. This study is a systematic review and meta-analysis of nine clinical studies. Total number of participants was 485 (earlier distributed total energy intakes: n = 244, later distributed total energy intakes; n = 241). Results show that energy intakes with a focus on earlier distribution resulted in significantly greater weight loss when compared with similarly energy-restricted diets with individuals consuming a larger proportion of their total energy intake later in the day and into the evening. Authors conclude that earlier energy intakes may be a promising tool to be used in conjunction with other weight loss strategies such as energy restriction to enhance weight loss. However, further research is required to elucidate the additional positive impacts that earlier distributed total energy intakes may have on weight and metabolic health.
Expert Review
Conflicts of interest:
None
Take Home Message:
Implementing a dietary strategy where a higher proportion of energy is consumed earlier in the day may offer additional benefits to an energy restricted diet for weight loss, blood glucose, improve markers of insulin resistance, increase satiety and improve hunger management. Based on the findings, earlier distribution of energy intake may serve as an effective component of a weight loss protocol.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Background
Chrononutrition refers to the timing and distribution of total daily energy intake across the day. It has been proposed that consuming a greater proportion of total daily energy intake earlier in the day as opposed to the evening may be beneficial for weight loss and metabolic health.
Aims
This systematic review and meta-analysis aimed to assess the impact of earlier versus later distribution of total daily energy intake on weight loss.
Results
A total of 9 randomised controlled trials involving 485 participants were included in this analysis. The study durations ranged from 5-16 weeks. All of the studies included in this analysis applied energy-restricted diets to both intervention arms. The mean percentages of energy intake in 8 of the 9 studies per meal were:
- Earlier distributed intakes: breakfast: 34% ± 16%, lunch: 38% ± 7%, dinner: 20% ± 6%.
- Later distributed intakes: breakfast: 19% ± 6%, lunch: 30% ± 10%, dinner; 40% ± 11%.
One of the studies advised percentage of energy intakes as either:
- Earlier: 70% for breakfast, morning tea and lunch and 30% for afternoon tea and dinner
- Late: 55% for breakfast, morning tea and lunch and 45% for afternoon tea and dinner.
The earlier distributed energy intake groups demonstrated significantly greater weight loss when compared with later distributed energy intake groups ( Mean Difference (MD) −1.23 kg; 95% CI −2.40, −0.06, p = 0.04;
I2 = 98%).
The earlier energy intake groups also displayed lower fasting and bedtime glucose levels (fasting: −0.83 vs. −0.27 mmol/L, p = 0.001; before sleep: −1.70 vs. −0.28 mmol/L, p = 0.009).
A random-effects model demonstrated that the earlier intake groups displayed greater reductions in LDL (MD: −0.11 mmol/L; 95% CI −0.14, −0.07, p < 0.01), fasting glucose (MD: 0.15 mmol/L, 95% CI −0.23, −0.06, p < 0.001) and HOMA-IR (MD: −0.38; 95% CI −0.64, −0.11, p = 0.005).
One study reported that earlier distribution energy intake also led to a greater reduction in medications following the intervention for type 2 diabetics (31% vs. 0%, P=0.002).
Two of the studies assessed both appetite and hunger and identified that earlier distribution of energy led to improvements in their urge to eat, preoccupation with food and cravings for sweets and fats.
Clinical practice applications:
Earlier distribution of energy intake may be beneficial for:
- Weight loss
- Improve fasting insulin, HOMA-IR, fasting glucose and HbA1c
- Reducing LDL
- Improving satiety and hunger management
- Supporting the reduction of medications for individuals with type 2 diabetes
- Improving regularity of sleep and waking times
Considerations for future research:
As the included studies only ranged from 5-16 weeks, longer duration studies would be useful to identify the effect of earlier distribution of energy intake on body weight, metabolic health and appetite over a longer period of time. There was a high degree of heterogeneity between the studies and a lack of uniformity in the distributions of energy intake across the day. Further studies with more uniformity of energy distribution would be needed to identify the optimal distribution of energy across the day to improve body weight and metabolic health.
Abstract
Consuming a greater proportion of total energy intake earlier in the day rather than in the evening is proposed to positively influence weight loss and health, potentially due to greater synchronization of human body circadian rhythms. This systematic review provides an update on existing evidence regarding earlier distributed eating patterns in weight loss interventions. Using a robust search strategy in five electronic databases, nine randomized controlled trials investigating the impact of energy intake distribution on weight loss were identified. Following critical appraisal, a random-effects meta-analyses found that, in the context of an energy-reduced diet, distributing energy intake with a focus on earlier intake resulted in significantly greater weight loss (-1.23 kg; 95% CI 2.40, -0.06, p = 0.04). Improvements in HOMA-IR, fasting glucose, and LDL cholesterol were also seen. The current study provides a timely update on the evidence linking distribution of total daily energy intake and health, showing that a focus on earlier intakes can result in greater short-term weight loss compared with later intakes. Future studies are needed to elucidate the impact that earlier intakes may have on weight management and metabolic health.
-
4.
The Effect of Regular Consumption of Reformulated Breads on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Schadow, AM, Revheim, I, Spielau, U, Dierkes, J, Schwingshackl, L, Frank, J, Hodgson, JM, Moreira-Rosário, A, Seal, CJ, Buyken, AE, et al
Advances in nutrition (Bethesda, Md.). 2023;14(1):30-43
-
-
-
-
Free full text
Plain language summary
The metabolic effect of bread depends on several qualitative aspects ranging from the type of grain, the amount of carbohydrates, levels of other nutrients, as well as the chemical structure and processing. The aim of this study was to assess the certainty of the evidence and to investigate the overall effect of regular consumption of reformulated breads on glycaemic control in the following groups: a) healthy adults; b) those at risk of developing cardiometabolic disease (e.g., having hypertension, hyperglycaemia, hypercholesterolemia and/or overweight/obesity); and c) those with manifest type 2 diabetes mellitus (T2DM). This study is a systematic review and meta-analysis of 22 studies and 23 distinct study populations. All studies were randomised controlled trials, 12 of which had a crossover design and 10 had a parallel design. In total, 1037 participants were included. These provided 669 and 595 data points for intervention and control comparisons, respectively. Results show a beneficial effect of reformulated bread variants on fasting blood glucose concentrations. This benefit may be more pronounced among people with manifest T2DM (low certainty of evidence). Authors conclude that bread quality is relevant for metabolic health among adults and that future studies should address its relevance among people at risk of T2DM.
Expert Review
Conflicts of interest:
None
Take Home Message:
This study’s findings suggest the effect of reformulated breads high in dietary fibre, whole grains, and/or functional ingredients may be more beneficial than regular breads on fasting blood glucose concentrations in adults, primarily among those with T2DM. Reformulated breads however, did not lower fasting insulin concentrations, HOMA-IR and HbA1C when compared to regular bread.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Overview
This study evaluated the effect of regular consumption of “reformulated breads” on glycemic control among healthy adults, adults at cardiometabolic risk or with manifest T2DM in 22 RCTs with 1037 participants. Compared with “regular” or comparator bread, consumption of reformulated intervention breads yielded lower fasting blood glucose concentrations only among people with T2DM (low certainty of evidence), yet no differences in fasting insulin, HOMA-IR, HbA1c, or postprandial glucose response were identified.
[*’reformulated bread’ as defined by the World Health Organisation of altering the processing or composition of a food to improve its nutritional profile, and contained whole-grains and dietary fibre]
Results
Sub group analysis revealed that the effect of reformulated breads high in dietary fibre, whole grains, and/or functional ingredients on lowering fasting blood glucose was confined to participants with T2DM, with no significant effect among participants without T2DM (0.68 mmol/L; 95% CI: 1.11, 0.36; I2 1⁄4 57% and 0.04 mmol/L; 95% CI: 0.13, 0.05; I2 1⁄4 25%, respectively; P < 0.001).
Subgroup analyses by continent revealed a more pronounced effect on fasting blood glucose concentrations in studies conducted in Asia and the Middle East compared with studies conducted in Europe, North America, and Oceania (MD: 0.84 mmol/L; 95% CI: 1.35, 0.33; I2 1⁄4 52% and MD: 0.04 mmol/L; 95% CI: 0.10, 0.03; I2 1⁄4 0%, respectively; P < 0.001)
Additional subgroup analyses found that the type of control bread, but not the type of intervention bread, affected the pooled effect estimate of fasting blood glucose concentration (P 1⁄4 0.03), with the largest difference reported in studies not describing the control bread used.
Limitations
Publication bias was considered negligible for the studies included in this meta-analysis, and the risk of bias assessment revealed that most of the studies had some concerns of risk of bias. One author is a member of the International Carbohydrate Quality Consortium and another is a member of the GRADE working group.
Strengths
This systematic review and meta-analysis include the focus on high-quality intervention studies (i.e., RCTs using either crossover or parallel design) and the inclusion of longer-term studies (>2 wk) to address the effectiveness of regular bread replacement for glycemic control in everyday life.
Clinical practice applications:
- This data suggests that bread quality is relevant for metabolic health among adults at risk of T2DM. In particular, reformulated breads were found to have a more beneficial impact than regular breads on fasting blood glucose concentrations in adults with TsDM. However, consumption of the reformulated bread (enriched with dietary fiber, whole grains, or functional ingredients) did not lower fasting insulin concentrations compared with the control breads (MD: 1.59 pmol/L; 95% CI: 5.78, 2.59; moderate certainty of evidence)
- Consumption of the reformulated bread did not lower HOMA-IR compared with the control breads (MD: 0.09; 95% CI: 0.35, 0.22; moderate certainty of evidence)
- Consumption of the reformulated bread did not lower HbA1c concentrations compared with the control bread (0.14; 95% CI: 0.39, 0.10; P 1⁄4 0.195; very low certainty of evidence).
Considerations for future research:
- Longer intervention periods may be required to determine the beneficial effects on the HbA1c concentrations and to elicit changes in markers of insulin resistance
- Future studies should use the 2022 WHO standardised HbA1c diagnostic reference criterion for diabetes mellitus
- Improvements in specific outcomes may also be linked to defined groups within populations such as persons with manifest T2DM.
- The type of reformulation of the bread may be an important factor but differ considerably around the world
Abstract
Bread is a major source of grain-derived carbohydrates worldwide. High intakes of refined grains, low in dietary fiber and high in glycemic index, are linked with increased risk for type 2 diabetes mellitus (T2DM) and other chronic diseases. Hence, improvements in the composition of bread could influence population health. This systematic review evaluated the effect of regular consumption of reformulated breads on glycemic control among healthy adults, adults at cardiometabolic risk or with manifest T2DM. A literature search was performed using MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials. Eligible studies employed a bread intervention (≥2 wk) in adults (healthy, at cardiometabolic risk or manifest T2DM) and reported glycemic outcomes (fasting blood glucose, fasting insulin, HOMA-IR, HbA1c, and postprandial glucose responses). Data were pooled using generic inverse variance with random-effects model and presented as mean difference (MD) or standardized MD between treatments with 95% CIs. Twenty-two studies met the inclusion criteria (n = 1037 participants). Compared with "regular" or comparator bread, consumption of reformulated intervention breads yielded lower fasting blood glucose concentrations (MD: -0.21 mmol/L; 95% CI: -0.38, -0.03; I2 = 88%, moderate certainty of evidence), yet no differences in fasting insulin (MD: -1.59 pmol/L; 95% CI: -5.78, 2.59; I2 = 38%, moderate certainty of evidence), HOMA-IR (MD: -0.09; 95% CI: -0.35, 0.23; I2 = 60%, moderate certainty of evidence), HbA1c (MD: -0.14; 95% CI: -0.39, 0.10; I2 = 56%, very low certainty of evidence), or postprandial glucose response (SMD: -0.46; 95% CI: -1.28, 0.36; I2 = 74%, low certainty of evidence). Subgroup analyses revealed a beneficial effect for fasting blood glucose only among people with T2DM (low certainty of evidence). Our findings suggest a beneficial effect of reformulated breads high in dietary fiber, whole grains, and/or functional ingredients on fasting blood glucose concentrations in adults, primarily among those with T2DM. This trial was registered at PROSPERO as CRD42020205458.
-
5.
Effects of exercise training programmes on fasting gastrointestinal appetite hormones in adults with overweight and obesity: A systematic review and meta-analysis.
Almesbehi, T, Harris, L, McGarty, A, Alqallaf, S, Westrop, S, Edwards, CA, Dorling, JL, Malkova, D
Appetite. 2023;182:106424
-
-
-
-
Free full text
Plain language summary
Appetite is controlled by several hormones including those of the gastrointestinal (GI) system. There has been controversy over whether exercise can affect these hormones resulting in altered food intake and this systematic review and meta-analysis aimed to address this. The results showed that 9 studies have been performed aimed at the effect of 16 different exercise interventions on appetite hormones of the GI system. Exercise had no effect on total ghrelin, acetylated ghrelin and peptide YY, however body mass index and body mass were significantly reduced in individuals with obesity or who are overweight. It was concluded that any increased appetite or energy intake during exercise interventions is unlikely related to GI appetite hormones. This study could be used by healthcare professionals to understand that although exercise may not affect food intake it can still aid weight loss in individuals who are overweight or obese.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This systematic review and meta-analysis found that exercise training programmes in individuals living with overweight and obesity have no impact on fasting concentrations of total and acylated ghrelin, PYY, GLP-1 and CCK.
- This finding suggests that any increase in appetite and energy intake typical of exercise training, would be related to different factors and not from changes in fasting concentrations of gastrointestinal appetite hormones.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Background
Overweight and obesity prevalence is increasing globally. Exercise is advocated as an effective preventive and treatment for obesity. However, exercise may affect appetite regulation, and understanding how this functions in people with overweight and obesity is of interest. Notably, the evidence regarding the effects of exercise training on gastrointestinal hormones such as ghrelin, has not been extensively synthesised.
Aim
- The aim of this systematic review and meta-analysis was therefore to synthesise the literature describing the effect of exercise programmes of >4 weeks’ duration from randomised controlled trials (RCT) on the fasting and gastrointestinal appetite hormones of adults living with overweight and obesity.
- The review followed PRISMA reporting guidelines and standard systematic review and meta analysis methodology.
Results
- After screening 13,204 records, nine studies with a total of 707 participants (259 men and 448 women) were identified that fit the pre-defined inclusion criteria and were included in the review.
- Overall, after exercise interventions in comparison to control, there was a reduction in body mass (effect size (d)= −0.22, 95% CI −0.42 to −0.03, p = 0.03; 7 studies) and BMI (d= −0.31, 95% CI −0.50 to −0.12, p = 0.001; 8 studies).
- Exercise had no impact on total fasting ghrelin (d = 1.06; 95% CI -0.38 to 2.5; p=0.15; 4 interventions) or fasting acylated ghrelin concentration (d = 0.08; 95% CI -0.31 to 0.47; p=0.68; 7 interventions).
- Fasting anorexigenic peptide YY did not differ between exercise and control (d = −0.16, 95% CI: −0.62 to 0.31, P = 0.51; 7 interventions).
- Two studies assessed the effects of exercise training on GLP-1 and meta-analyses were not possible. In one study, fasting GLP-1 was higher in the intervention group (p=0.04) though the other study found no difference (P>0.05). Only one study looked at fasting plasma cholecystokinin (CCK), which found no change between exercise and control interventions (p>0.5).
- When looking at the correlation between body mass and appetite hormone changes, weight loss (p<0.05) and BMI reduction (p<0.05) occurring with exercise was positively associated with an increase in total plasma ghrelin (p<0.05); increased ghrelin was associated to reductions in body weight and BMI (both p<0.0001). Further, one study reported a positive correlation of body mass loss and BMI reduction with a reduction in acylated ghrelin (p=0.003 and 0.009, respectively) and negatively with an increase in plasma PYY concentration (p=0.003 and 0.03, respectively).
Clinical practice applications:
This systematic review suggested that any compensatory increase in energy intake due to exercise training is unlikely to be related to fasting gastrointestinal appetite hormone changes. Therefore, nutritional therapists should bear this in mind when consulting with clients and find personalised lifestyle strategies to help people manage their caloric consumption in relation to exercise training.
Considerations for future research:
- The relation between changes in body mass or BMI and fasting appetite hormones could not be fully explored due to the small number of studies included in this review. Moreover, the results of this review should be interpreted with caution because most studies were underpowered with a high risk of bias, and there was considerable heterogeneity within some meta-analyses. The effect of exercise training on gastrointestinal satiety hormones including ghrelin, PYY, and CCK therefore require further investigation in individuals living with overweight and obesity, in order to reach more substantial conclusions.
- Exercise enhances the coupling between energy intake and energy expenditure after food consumption, where controlled studies are needed to test how postprandial concentrations of gastrointestinal hormones are influenced by exercise training in individuals with overweight and obesity.
Abstract
A systematic review and meta-analysis was performed to determine the effect of exercise training on fasting gastrointestinal appetite hormones in adults living with overweight and obesity. For eligibility, only randomised controlled trials (duration ≥ four weeks) examining the effect of exercise training interventions were considered. This review was registered in the International Prospective Register of Systematic Reviews (CRD42020218976). The searches were performed on five databases: MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus. The initial search identified 13204 records. Nine studies, which include sixteen exercise interventions, met the criteria for inclusion. Meta-analysis was calculated as the standardised mean difference (Cohen's d). Exercise training had no effect on fasting concentrations of total ghrelin (d: 1.06, 95% CI -0.38 to 2.50, P = 0.15), acylated ghrelin (d: 0.08, 95% CI: -0.31 to 0.47, P = 0.68) and peptide YY (PYY) (d = -0.16, 95% CI: -0.62 to 0.31, P = 0.51) compared to the control group. Analysis of body mass index (BMI) (d: -0.31, 95% CI: -0.50 to -0.12, P < 0.01) and body mass (d: -0.22, 95% CI: -0.42 to -0.03, P = 0.03) found a significant reduction after exercise compared to controls. Overall, exercise interventions did not modify fasting concentrations of total ghrelin, acylated ghrelin, and PYY in individuals with overweight or obesity, although they reduced body mass and BMI. Thus, any upregulation of appetite and energy intake in individuals with overweight and obesity participating in exercise programmes is unlikely to be related to fasting concentrations of gastrointestinal appetite hormones.
-
6.
Influence of water-based exercise on energy intake, appetite, and appetite-related hormones in adults: A systematic review and meta-analysis.
Grigg, MJ, Thake, CD, Allgrove, JE, King, JA, Thackray, AE, Stensel, DJ, Owen, A, Broom, DR
Appetite. 2023;180:106375
-
-
-
-
Free full text
Plain language summary
Exercise is an effective way to improve mental and physical health and can influence weight management due to the energy expenditure. Energy balance is influenced by day-to-day variations in energy intake and expenditure. The aim of this study was to address whether water-based exercise influences energy intake, appetite, and appetite related hormones differently to land based exercise in adults. This study is a systematic review and meta-analysis of nine studies which include randomised crossover ( 7 trials), semi-random (1 trial) (water-trial was required prior to iso-energetically matched water trial) and independent group (1 trial) (used in the 12-week study) designs. Results show that post-exercise energy intake is higher after water-based exercise versus a resting control. However, there wasn’t any difference in energy intake when water-based exercise was compared with land-based exercise. Furthermore, when different water temperatures were analysed, post-exercise energy intake was higher in cold water versus neutral water. Additionally, cycling and swimming did not alter fasting plasma concentrations of appetite regulating hormones (ghrelin and leptin), insulin or total peptide YY [gut hormone] but contributed to body mass loss. Authors conclude that if body mass management is a person’s primary focus, it is important to be mindful of the tendency to eat more in the subsequent hours after water-based exercise, as energy intake may be increased when compared to a no exercise control.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The only type of exercise reporting an increase in energy intake was in water-based activities, where the temperature was between 18-20• C. However, this was only when explored in comparison to a resting control. No difference was reported in energy intake when water-based exercise was compared with land-based exercise.
- Any form of exercise, whether land or water-based should be considered where appropriate to reduce the risks of sedentary behaviour.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction:
Exercise is effective for weight-management alongside other physical and mental health benefits. Changes in appetite-regulating hormones may affect energy balance, e.g. some exercise may suppress appetite, known as exercise-induced anorexia. This review evaluated differences in energy intake, appetite and appetite-related hormones in land-based versus water-based exercise.
Methods:
The meta-analysis followed PRISMA guidelines and was registered on PROSPERO. Literature searching resulted in eight studies published between 1991 and 2021, which met the inclusion criteria (water v control), 5 studies (water v land) and 2 studies (water at different temperatures). Risk of Bias was assessed using Cochrane’s Risk of Bias for randomised trials.
Results:
Data were analysed in RevMan 5.4.1 using fixed effects, generic inverse variance method on energy intake. High heterogeneity prevented analysis on appetite and appetite-related hormones. Standard deviation was inputted based on estimated values for missing data. Heterogeneity was calculated using the I2 index. Sensitivity analyses were conducted. Statistical significance was set at p<0.05 and analyses based on two-tailed Z tests.
All participants had a healthy BMI, were aged 19-39 and ranged from well-trained to non-exercisers. A single bout of water-based exercise increased ad-libitum energy intake compared to a non-exercise control (mean difference [95% CI]: 330 [118, 542] kJ, P = 0.002) but no difference was identified between water and land-based exercise (78 [-176, 334] kJ, P = 0.55). Cold water exercise (18–20 •C) increased energy intake more than neutral water (27–33 •C) temperature (719 [222, 1215] kJ; P < 0.005). One 12-week study reported cycling and swimming did not alter fasting plasma concentrations of total ghrelin, insulin, leptin or total PYY but contributed to body mass loss 87.3 (5.2) to 85.9 (5.0) kg and 88.9 (4.9) to 86.4 (4.5) kg (P < 0.05) respectively.
Conclusion:
Despite limitations, this review may provide preliminary evidence on energy intake and appetite for water-based activities. If weight management is a primary focus, then water temperature needs to be considered, particularly if sub 20•C .
Clinical practice applications:
Although this study suggests cold water exercise may cause an increase in energy intake, 95% confidence intervals for individual studies are very large so results should be interpreted cautiously. Those preferring exercise in cold water, should be encouraged, providing they are mindful of the tendency to eat more post-exercise.
It is not possible to draw any robust conclusions about the ratings of hunger in response to different types of exercise due to limited data. However, according to the review, five studies demonstrated that hunger was suppressed more than control prior at the start of water-based exercise, and during and immediately after exercise.
Considerations for future research:
Most participants were of healthy weight and physically active, however since appetite signals may be dysregulated in obesity, including all weight categories and different activity levels may generate a more comprehensive overview.
Further research recommendations include:
- Measuring the effects of water- based activities on appetite, appetite related hormones and energy intake at different time points following exercise in order to provide recommendations for effective weight management strategies and in a range of different temperatures.
- Using a ‘no exercise’ water immersion control. Evidence suggests that immersion in cold water alone may increase energy expenditure
- Evaluating the effect of a water-based activity, such as swimming performed in a ‘fasted’ and ‘non-fasted’ state to investigate the impact on appetite, appetite related hormones and energy intake.
Abstract
Single bouts of land-based exercise suppress appetite and do not typically alter energy intake in the short-term, whereas it has been suggested that water-based exercise may evoke orexigenic effects. The primary aim was to systematically review the available literature investigating the influence of water-based exercise on energy intake in adults (PROSPERO ID number CRD42022314349). PubMed, Medline, Sport-Discus, Academic Search Complete, CINAHL and Public Health Database were searched for peer-reviewed articles published in English from 1900 to May 2022. Included studies implemented a water-based exercise intervention versus a control or comparator. Risk of bias was assessed using the revised Cochrane 'Risk of bias tool for randomised trials' (RoB 2.0). We identified eight acute (same day) exercise studies which met the inclusion criteria. Meta-analysis was performed using a fixed effects generic inverse variance method on energy intake (8 studies (water versus control), 5 studies (water versus land) and 2 studies (water at two different temperatures)). Appetite and appetite-related hormones are also examined but high heterogeneity did not allow a meta-analysis of these outcome measures. We identified one chronic exercise training study which met the inclusion criteria with findings discussed narratively. Meta-analysis revealed that a single bout of exercise in water increased ad-libitum energy intake compared to a non-exercise control (mean difference [95% CI]: 330 [118, 542] kJ, P = 0.002). No difference in ad libitum energy intake was identified between water and land-based exercise (78 [-176, 334] kJ, P = 0.55). Exercising in cold water (18-20 °C) increased energy intake to a greater extent than neutral water (27-33 °C) temperature (719 [222, 1215] kJ; P < 0.005). The one eligible 12-week study did not assess whether water-based exercise influenced energy intake but did find that cycling and swimming did not alter fasting plasma concentrations of total ghrelin, insulin, leptin or total PYY but contributed to body mass loss 87.3 (5.2) to 85.9 (5.0) kg and 88.9 (4.9) to 86.4 (4.5) kg (P < 0.05) respectively. To conclude, if body mass management is a person's primary focus, they should be mindful of the tendency to eat more in the hours after a water-based exercise session, particularly when the water temperature is cold (18-20 °C).
-
7.
Effect of polyphenol compounds on Helicobacter pylori eradication: a systematic review with meta-analysis.
Wang, Q, Yao, C, Li, Y, Luo, L, Xie, F, Xiong, Q, Feng, P
BMJ open. 2023;13(1):e062932
-
-
-
Free full text
Expert Review
Conflicts of interest:
None
Take Home Message:
- This is the first meta-analysis of polyphenol efficacy and safety in eradicating H. pylori.
- The results suggest that polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) can improve eradication rates.
- Furthermore, polyphenol compounds combined with standard triple therapy for H.pylori infection can significantly improve eradication (p=0.03).
- No evidence for an increased rate of side effects could be found.
- Due to the low quality of the included studies, these results should be interpreted with caution.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Background
The authors highlight that Helicobacter pylori (H. pylori) has been classified as a group 1 carcinogen and H. pylori infection is considered the leading cause of gastric cancer. More than half the world’s population is infected with H. pylori and recurrence rates have increased over the past decade. Several studies indicate that polyphenol compounds positively affect H. pylori eradication. However, experimental and clinical studies have shown different results.
Methods
- This is the first meta-analysis to assess the efficacy and safety of polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) in eradicating H. pylori.
- A total of 12 RCTs with 1251 adult participants were finally included. Two studies evaluated the efficacy of curcumin, four studies evaluated the efficacy of cranberry, four studies assessed the efficacy of liquorice, one study evaluated the efficacy of garlic, and one study assessed the efficacy of broccoli.
- Subgroup analysis of different treatment schemes on the eradication rate of H.pylori infection included: three studies which compared the effects of polyphenols with placebo; six studies compared the effects of polyphenols along with triple therapy; two studies compared the effects of polyphenol plus triple therapy with bismuth triple therapy; one study compared the effects of polyphenols plus quadruple regimen with quadruple regimen plus placebo.
Results
- The results indicate that polyphenols are conducive to H. pylori eradication. The total eradication rate of H.pylori in the polyphenol compounds group was significantly higher than in the group without polyphenol compounds (RR 1.19, 95% CI 1.03 to 1.38, p=0.02).
- In subgroup analyses, eradication rate with polyphenol therapy was superior to that without polyphenol therapy in the polyphenols versus placebo subgroup (RR 4.23, 95% CI 1.38 to 12.95, p=0.01) and in the polyphenols plus triple therapy versus triple therapy subgroup (RR 1.11, 95% CI 1.01 to 1.22, p=0.03).
- No significant differences existed between the five different polyphenol compounds analysed.
- The most frequent adverse effects of polyphenol compounds included diarrhoea, headache and vomiting. However, there were no differences regarding side effects between the polyphenol compounds and control groups (RR 1.47, 95% CI 0.83 to 2.58, p=0.18).
Limitations:
- Only the eradication rate of H. pylori infection according to different treatment schemes and polyphenol compounds was analysed, with no analysis of polyphenol dose.
- Visual inspection of the funnel plot suggested that publication bias existed. Most studies ignored possible adverse reactions, and safety observations could be improved.
- The number of cases included in this meta-analysis is small and the methodological quality of the included trials was generally poor.
- The results of subgroup analyses on different treatment schemes and polyphenol compound species seem more inconclusive due to the small number of studies that could be included.
- The polyphenol contents of each food before and after the eradication period from each study could not be determined which might work as a confounding factor. This confounding factor may have an impact on the final result.
Clinical practice applications:
- Infection with H.pylori is a major pathogenic factor for many gastrointestinal conditions such as chronic atrophic gastric ulcers and has been linked with several extra-digestive diseases such as atherosclerosis, Alzheimer’s disease and rosacea.
- The efficacy of standard 1-week triple therapy containing clarithromycin and either metronidazole or amoxicillin combined with a PPI has decreased dramatically, with eradication rates as low as 50%–70%. Antibiotic resistance and patient compliance are the major causes of this decline.
- Concomitant, sequential and hybrid therapies are also recommended for treating H. pylori infection. However, there are currently few, if any, regimens which consistently achieve eradication rates exceeding 90%. In this analysis H. pylori eradication rates ranged from 54.4% to 91.7% in the polyphenol treatment groups.
- The results of this analysis indicate that polyphenol compounds can significantly improve H. pylori eradication rates and might be more effective during polyphenol treatment combined with standard triple therapy.
- No evidence for an increased rate of side effects could be found.
- Due to the low quality of the included studies, these results should be interpreted with caution.
Considerations for future research:
- While a few included studies mention doses of these polyphenol compounds for eradicating H. pylori, it was not an outcome analysed in this meta-analysis and therefore future research on this would help to clarify appropriate dosages.
- Adverse reactions and safety observations warrant further study.
- More large-scale, high-quality clinical trials should be conducted to provide a stronger, evidence-based foundation for guiding clinical medication. In particular in relation to more studies on different treatment schemes and species.
- Finally, the polyphenol contents of each food before and after the eradication period from each manuscript included in the analysis could not be determined which could be a confounding factor. Future studies should address this.
Abstract
OBJECTIVES Polyphenol compounds are classified as organic compounds with phenolic units exhibiting a variety of biological functions. This meta-analysis aims to assess the efficacy and safety of polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) in eradicating Helicobacter pylori. DESIGN Systematic review and meta-analysis. METHODS Literature searches were conducted on PubMed, Embase, The Cochrane Library, Web of Science, Medline, Chinese National Knowledge Infrastructure database, Chinese Scientific Journal Database and Wan Fang database from inception to January 2022. All randomised controlled trials comparing polyphenol compounds with the placebo or used as an adjunct treatment are included in this meta-analysis.The treatment effect for dichotomous outcomes was assessed using risk ratio (RR), while for continuous outcomes, mean differences both with 95% CIs, were used. Subgroup analyses were carried out for different treatment schemes and polyphenol compound species. RESULTS 12 trials were included in the meta-analysis. The total eradication rate of H.pylori in the polyphenol compounds group was higher than in the group without polyphenol compounds. Statistical significance was also observed (RR 1.19, 95% CI 1.03 to 1.38, p=0.02). The most frequent adverse effects of polyphenol compounds included diarrhoea, headache and vomiting. However, there were no differences regarding side effects between the two groups (RR 1.47, 95% CI 0.83 to 2.58, p=0.18). In subgroup analyses, the H.pylori eradication rate regimens with polyphenols therapy was superior to that of regimens without polyphenols therapy in the polyphenols versus placebo subgroup (RR 4.23, 95% CI 1.38 to 12.95, p=0.01), polyphenols plus triple therapy versus triple therapy subgroup (RR 1.11, 95% CI 1.01 to 1.22, p=0.03). CONCLUSION Polyphenol compounds can improve H.pylori eradication rates. Polyphenol compounds plus standard triple therapy can significantly improve the eradication. However, no evidence of a higher incidence of side effects could be found. PROSPERO REGISTRATION NUMBER CRD42022307477.
-
8.
Predictive metabolites for incident myocardial infarction: a two-step meta-analysis of individual patient data from six cohorts comprising 7897 individuals from the COnsortium of METabolomics Studies.
Nogal, A, Alkis, T, Lee, Y, Kifer, D, Hu, J, Murphy, RA, Huang, Z, Wang-Sattler, R, Kastenmüler, G, Linkohr, B, et al
Cardiovascular research. 2023;119(17):2743-2754
-
-
-
-
Free full text
-
Plain language summary
Heart disease is a major cause of death worldwide. Individuals at risk are usually identified by the presence of diseases such as obesity and diabetes, and lifestyle factors such as smoking. However, there is a new understanding that when the body converts food into energy it creates by-products which might play an important role in the development of heart disease. Better understanding of these may be able to aid the identification of individuals at risk. This analysis of 7897 participants from 6 different cohort studies aimed to determine biomarkers associated with a heart attack. The results showed there were 56 metabolites associated with heart attack, some of which were associated with an increased occurrence and some a decreased occurrence. Most of the identified metabolites were lipids. Metabolites involved in bile acid production and amino acids were also identified. It was concluded that these metabolites may act as an indicator for individuals who are at risk of heart attack, however further research is needed. This study could be used by healthcare professionals to understand that the science behind the use of metabolites to indicate risk for heart attack is developing but still in its infancy.
Expert Review
Conflicts of interest:
None
Take Home Message:
- There are certain lipids and amino acids that are associated with the incidence of MI, but the use of these to identify people at risk of MI is still in its infancy
- Current proven strategies to identify those at risk should take precedence over the measurement, identification and use of metabolites. However, this area of research is of current interest.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
Individuals at risk of cardiovascular disease are usually identified by the presence of comorbidities (e.g. obesity and diabetes), and lifestyle factors (e.g. smoking). However, there is a new understanding that certain metabolites may be associated with myocardial infarction (MI) and a better understanding of these may be able to aid the identification of individuals at risk. This meta-analysis aimed to determine metabolites associated with a MI.
Methods
- This meta-analysis of 6 cohort studies from the USA and Europe involved 7897 participants
- The primary outcome was the metabolites associated with incident MI
- The secondary outcome was the metabolites associated with prevalent MI
- A total of 1442 metabolites were measured.
Results
- There were 1373 MI cases from the studies
- The results showed that there were 56 metabolites associated with MI, 42 had a direct association and 14 had an inverse relationship
- Most of the identified metabolites were lipids (n=21) and amino acids (n=17)
- Of the lipids, 3-methyladipate and 1-palmitoyl-2-linoleoyl-glycerol (16:0/18:2) were associated with a higher risk of MI (HR estimates ranged from 1.28; 95% confidence interval (CI) = 1.13–1.44, P < 0.001 to 1.21; 95% CI = 1.08–1.35, P = <0.005 respectively)
- Of the amino acids, 4-hydroxyphenylacetate and cystathionine had the largest increase in risk (HR estimates 1.24; 95% CI = 1.11–1.38, P = <0.01 and 1.2; 95% CI = 1.07–1.35, P = <0.01 respectively)
- When the meta-analysis was stratified by race, it showed that out of the 56 metabolites identified, the majority were associated with white individuals (n=41), whereas only 18 were associated with black individuals. Of these, 3 were specific to individuals with an African ancestry.
Conclusion
- It was concluded that certain metabolites and their associated pathways may help to identify individuals at risk for MI before disease onset and lead to better prevention
Clinical practice applications:
- Research into metabolite association with increased risk of MI is still in its infancy and has little merit until we understand the mechanisms involved and the direction of causation
- It does however give an idea of the tools that may be developed in the future that will aid identification and help to develop prevention strategies
- The metabolites associated with MI may be racially specific and further understanding is needed on this. Hence the data should be interpreted with caution.
Considerations for future research:
- Whilst associations are indicative of relationships, they do not identify causation. Future research should focus on the pathways which may link the metabolites with MI
- Identifying these pathways will also help to develop prevention strategies pertinent to specific nutrients
- A better understanding of how metabolites may be racially distinct is also required.
Abstract
AIMS: Myocardial infarction (MI) is a major cause of death and disability worldwide. Most metabolomics studies investigating metabolites predicting MI are limited by the participant number and/or the demographic diversity. We sought to identify biomarkers of incident MI in the COnsortium of METabolomics Studies. METHODS AND RESULTS We included 7897 individuals aged on average 66 years from six intercontinental cohorts with blood metabolomic profiling (n = 1428 metabolites, of which 168 were present in at least three cohorts with over 80% prevalence) and MI information (1373 cases). We performed a two-stage individual patient data meta-analysis. We first assessed the associations between circulating metabolites and incident MI for each cohort adjusting for traditional risk factors and then performed a fixed effect inverse variance meta-analysis to pull the results together. Finally, we conducted a pathway enrichment analysis to identify potential pathways linked to MI. On meta-analysis, 56 metabolites including 21 lipids and 17 amino acids were associated with incident MI after adjusting for multiple testing (false discovery rate < 0.05), and 10 were novel. The largest increased risk was observed for the carbohydrate mannitol/sorbitol {hazard ratio [HR] [95% confidence interval (CI)] = 1.40 [1.26-1.56], P < 0.001}, whereas the largest decrease in risk was found for glutamine [HR (95% CI) = 0.74 (0.67-0.82), P < 0.001]. Moreover, the identified metabolites were significantly enriched (corrected P < 0.05) in pathways previously linked with cardiovascular diseases, including aminoacyl-tRNA biosynthesis. CONCLUSIONS In the most comprehensive metabolomic study of incident MI to date, 10 novel metabolites were associated with MI. Metabolite profiles might help to identify high-risk individuals before disease onset. Further research is needed to fully understand the mechanisms of action and elaborate pathway findings.
-
9.
Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials.
Zheng, Y, Zhang, Z, Tang, P, Wu, Y, Zhang, A, Li, D, Wang, CZ, Wan, JY, Yao, H, Yuan, CS
Frontiers in immunology. 2023;14:1143548
-
-
-
-
Free full text
Plain language summary
Intestinal barrier function is closely related to the pathogenesis of various immune and inflammatory diseases. The intestinal microbiota plays an essential role in maintaining gut homeostasis and functionality in the presence of pro-inflammatory and anti-inflammatory microbes. The aim of this study was to comprehensively evaluate the role of probiotics in contributing to intestinal barrier function, and the related immune function, inflammatory status, and gut microbiota composition. This study was a systematic review of 28 articles (qualitative synthesis), and a meta-analysis of 26 randomised controlled trials. Results showed that probiotics could significantly improve intestinal barrier function according to specific indicators. The meta-analysis also indicated that probiotic supplementation could reduce inflammatory factors. Furthermore, it also demonstrated that probiotics could modulate gut microbiota compositions by elevating the abundances of Bifidobacterium and Lactobacillus. Authors conclude that probiotics could improve intestinal barrier function to some extent, but more high-quality randomised controlled studies are needed to reach a solid conclusion.
Expert Review
Conflicts of interest:
None
Take Home Message:
The probiotics Bifidobacterium and Lactobacillus may be beneficial for health by addressing imbalances in gut bacteria (dysbiosis), reducing inflammation in the gut and improving the integrity and function of the gut barrier
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
Probiotics are microorganisms that are considered beneficial to health. The aim of this study was to assess the role of probiotics in protecting intestinal barrier function as well as their effects on the composition of gut microbiota, inflammatory status, and immune function for reducing the risk of related diseases.
Methods
26 randomised controlled trials (RCTs) published between 2005-2021 with a total population of n=1891 (n = 955 Intervention, n = 936 controls)) were included in the meta-analysis. Outcome measures were categorised under indicators relating to intestinal barrier function, inflammatory markers, immune function and microbiota composition. Studies were conducted worldwide with participants being healthcare patients or athletes. Study durations ranged from 3 days to 6 months. Different dosages and forms of probiotics were used. Data was pooled for Bifidobacterium, Lactobacillus, Enterobacteriaceae and Enterococcus species.
Results
Gut barrier function in the probiotic groups was improved as measured by transepithelial resistance (TER) mean difference (MD) 5.27 {95% CI, 3.82 to 6.72, p = < 0.00001], lipopolysaccharide (LPS) standardised mean difference (SMD) -0.47 (95% CI, -0.85 to -0.09, p = 0.02), serum zonulin SMD -1.58 (95% CI,-2.49 to -0.66, p = 0.0007), and endotoxin SMD -3.20 (95% CI, -5.41 to - 0.98, p = 0.005).
The inflammatory markers interleukin 6 (IL-6), C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-a) were also improved compared to control groups. Lactobacillus (95% CI p=0.02) and Bifidobacterium (95% CI, p=0.01) enhanced microbial composition, however, Enterobacteriaceae and Enterococcus species did not. Immune function as measured by Immunoglobulin A (IgA), Immunoglobulin G IgG and Immunoglobulin M (IgM) were not improved.
Conclusion
The findings of this study suggest that intestinal barrier function and microbial composition could be improved using probiotics. They were also found to help alleviate inflammation. Further studies of high quality are however needed to confirm these results.
No conflicts of interest were reported.
Clinical practice applications:
The use of the probiotics Bifidobacterium and Lactobacillus may be beneficial for:
- supporting the integrity of gut barrier function
- improving the composition of gut microbiota
- lowering inflammation
Considerations for future research:
High heterogeneity between studies may affect the applicability of the results. Future research development should focus on the following areas:
- testing methods
- study durations
- measuring indicators
- the type and dose of probiotics
Abstract
BACKGROUND Probiotics play a vital role in treating immune and inflammatory diseases by improving intestinal barrier function; however, a comprehensive evaluation is missing. The present study aimed to explore the impact of probiotics on the intestinal barrier and related immune function, inflammation, and microbiota composition. A systematic review and meta-analyses were conducted. METHODS Four major databases (PubMed, Science Citation Index Expanded, CENTRAL, and Embase) were thoroughly searched. Weighted mean differences were calculated for continuous outcomes with corresponding 95% confidence intervals (CIs), heterogeneity among studies was evaluated utilizing I2 statistic (Chi-Square test), and data were pooled using random effects meta-analyses. RESULTS Meta-analysis of data from a total of 26 RCTs (n = 1891) indicated that probiotics significantly improved gut barrier function measured by levels of TER (MD, 5.27, 95% CI, 3.82 to 6.72, P < 0.00001), serum zonulin (SMD, -1.58, 95% CI, -2.49 to -0.66, P = 0.0007), endotoxin (SMD, -3.20, 95% CI, -5.41 to -0.98, P = 0.005), and LPS (SMD, -0.47, 95% CI, -0.85 to -0.09, P = 0.02). Furthermore, probiotic groups demonstrated better efficacy over control groups in reducing inflammatory factors, including CRP, TNF-α, and IL-6. Probiotics can also modulate the gut microbiota structure by boosting the enrichment of Bifidobacterium and Lactobacillus. CONCLUSION The present work revealed that probiotics could improve intestinal barrier function, and alleviate inflammation and microbial dysbiosis. Further high-quality RCTs are warranted to achieve a more definitive conclusion. CLINICAL TRIAL REGISTRATION https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=281822, identifier CRD42021281822.
-
10.
The effects of probiotic and synbiotic supplementation on inflammation, oxidative stress, and circulating adiponectin and leptin concentration in subjects with prediabetes and type 2 diabetes mellitus: a GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials.
Naseri, K, Saadati, S, Ghaemi, F, Ashtary-Larky, D, Asbaghi, O, Sadeghi, A, Afrisham, R, de Courten, B
European journal of nutrition. 2023;62(2):543-561
-
-
-
-
Free full text
-
Plain language summary
When acute, inflammation is a necessary function of the immune system allowing the body to recognise and remove foreign stimuli. However, when chronic inflammation occurs, it can contribute to and exacerbate diseases such as type 2 diabetes (T2D). The gut microbiota and the use of probiotics has been shown to modulate processes within the body and decrease chronic inflammation, however research has not consistently shown this and an inverse relationship has been shown in some studies. This systematic review and meta-analysis aimed to determine the effect of probiotics and synbiotics on inflammation in individuals with prediabetes and T2D. A total of 32 randomised control trials were included in the meta-analysis and showed that certain, but not all inflammatory markers were reduced. Antioxidants were increased. The effect was especially pronounced in individuals with T2D as opposed to prediabetes. It was concluded that probiotics or synbiotics could be useful for individuals with T2D to reduce inflammation and reduce the risk for other associated diseases such as heart disease.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Probiotic and synbiotic supplementation may significantly reduce inflammation and oxidative stress, potentially lowering the risk of cardiovascular diseases in those with prediabetes and T2DM.
- These supplements may be particularly beneficial for individuals with T2DM and those who are overweight or obese.
- Incorporating probiotics and synbiotics into the diet could be a supportive strategy for improving metabolic health markers.
- The observed benefits vary depending on the type and duration of supplementation, suggesting that consistent, long-term use might be necessary to achieve noticeable health improvements.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
This systematic review meta-analysis and meta-regression assessed the impact of probiotics and synbiotics on inflammation, antioxidants, oxidative stress, and adipokines in prediabetes and type 2 diabetes.
Methodology
The methodology involved searching PubMed/MEDLINE, ISI Web of Science, Scopus, and Cochrane Library databases without date or language restrictions until March 2022. Study quality was evaluated.
- Inclusion criteria: Adults 18+ with prediabetes or type 2 diabetes; interventions with probiotics or synbiotics versus placebo or other treatments; and reporting on inflammatory biomarkers, adipocytokines, and oxidative stress serum biomarkers in RCTs with parallel or cross-over designs.
Results
32 RCTs with 2074 participants were analysed, mostly in Asia (26 studies) and 5 in Europe, Africa, Oceania, and America, over 4 to 24 weeks. Dosages varied, including synbiotic bread with Lactobacillus sporogenes and inulin (1×10^8 CFU, 0.07g/g, thrice daily), 300ml/day fermented milk with L. helveticus, daily synbiotic and probiotic tablets, a probiotic mixture (120g/day), synbiotics (9g, thrice daily), multistrain probiotic yoghurt (300g/day), L. sporogenes-enriched bread (40g, thrice daily), and probiotic honey (2500mg/day). Measurements included CRP (31 RCTs), TNF-α (12 RCTs), GSH (13 RCTs), MDA (12 RCTs), TAC (11 RCTs), and NO levels (8 trials).
Effects of probiotics and synbiotics:
- significantly reduced CRP levels (-0.62 mg/L, 95% CI: -0.80 to -0.44, p < 0.001, 31 RCTs), showing greater efficacy in T2DM than prediabetes, particularly in individuals with overweight.
- TNF-α levels decreased in participants with T2D or overweight (-0.48 pg/mL, 95% CI: -0.81 to -0.15, p = 0.004, 12 RCTs).
- GSH levels significantly rose (69.80, 95% CI: 33.65 to 105.95, p < 0.001, 13 RCTs), independent of trial duration or baseline BMI.
- MDA levels were significantly reduced (-0.51, 95% CI: -0.73 to -0.30, p < 0.001, 12 RCTs) in studies lasting ≥12 weeks.
- TAC significantly increased (73.59, 95% CI: 33.24 to 113.95, p < 0.001, 11 RCTs), with more pronounced effects in longer trials and with probiotics.
- NO levels improved significantly (7.49, 95% CI: 3.12 to 11.86, p = 0.001, 9 trials) in individuals with obesity.
- Positive impacts on CRP, TNF-α, MDA, and TAC were more marked in trials ≥12 weeks.
Conclusions
Probiotic or synbiotic intake may benefit those with prediabetes and T2DM, reducing CRP, TNF-α, MDA, and enhancing TAC, GSH, NO levels, especially in T2DM individuals. Effects are stronger in individuals with overweight or obesity.
Clinical practice applications:
- Probiotic and synbiotic supplementation could be recommended to reduce inflammatory biomarkers like CRP and TNF-α, especially in individuals with T2DM.
- The improvements in oxidative stress markers, such as increased TAC and GSH and decreased MDA, support the use of probiotic and synbiotic supplements in managing oxidative stress in T2DM and prediabetes.
- Longer durations (≥12 weeks) of probiotic or synbiotic supplementation may offer a more pronounced effect on antioxidant capacity.
- The findings can guide personalised nutritional recommendations, as for example improvement in inflammation biomarkers and NO were more evident in individuals with T2DM or overweight suggesting an anti-inflammatory effect primarily in these groups. Moreover, markers related to antioxidant capacity were improved in those diagnosed with prediabetes or T2DM irrespective of BMI.
Considerations for future research:
- The beneficial effects on inflammatory and antioxidant/oxidative stress markers suggest a need for larger and longer-term studies to solidify the role of probiotics and synbiotics in benefiting chronic conditions like T2DM and prediabetes.
- There is potential for investigating the specific strains of probiotics that are most effective, considering varying outcomes observed across different studies.
- Research could explore the mechanisms by which probiotics and synbiotics exert their beneficial effects, contributing to a better understanding of gut-health interactions.
- The varying responses based on BMI categories indicate a need for personalised nutrition research to optimise probiotic therapy for individual needs.
- Future studies should consider standardising the dosage and formulation of probiotics to determine the most effective therapeutic doses and combinations.
Abstract
PURPOSE Probiotics or synbiotics consumption have been suggested to reduce the risk of cardiovascular disease (CVD) through a decline in inflammation and oxidative stress, however, the results from studies are conflicting. This study filled this knowledge gap by evaluating randomized controlled trials (RCTs) investigating probiotics or synbiotics intake on adipokines, inflammation, and oxidative stress in patients with prediabetes and type-2 diabetes mellitus (T2DM). METHODS We systematically did search up to March 2022 in PubMed/Medline, Scopus, ISI Web of Science, and Cochrane library. A random-effect model was applied to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each outcome. RESULTS A total of 32 RCTs were included in the meta-analysis. This intervention led to a significant decrease in levels of C-reactive protein (CRP) (WMD - 0.62 mg/l; 95% CI - 0.80, - 0.44; p < 0.001), tumor necrosis factor-α (TNF-α) (WMD - 0.27 pg/ml; 95% CI - 0.44, - 0.10; p = 0.002) and malondialdehyde (MDA) (WMD - 0.51 µmol/l; 95% CI - 0.73, - 0.30; p < 0.001), and also a significant increase in levels of glutathione (GSH) (WMD 69.80 µmol/l; 95% CI 33.65, 105.95; p < 0.001), total antioxidant capacity (TAC) (WMD 73.59 mmol/l; 95% CI 33.24, 113.95; p < 0.001) and nitric oxide (NO) (WMD 7.49 µmol/l; 95% CI 3.12, 11.86; p = 0.001), without significant alterations in interleukin-6 (IL-6) and adipokines levels. CONCLUSION A consumption of probiotics or synbiotics could be a useful intervention to improve cardiometabolic outcomes through a reduced inflammation and oxidative stress in patients with prediabetes and T2DM.