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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
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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:
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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 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.
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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
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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:
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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:
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.
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3.
Effects of Omega-3 Fatty Acids Supplementation on Serum Lipid Profile and Blood Pressure in Patients with Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Liu, YX, Yu, JH, Sun, JH, Ma, WQ, Wang, JJ, Sun, GJ
Foods (Basel, Switzerland). 2023;12(4)
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Metabolic syndrome (MetS) is a group of disorders that cause disturbed metabolism, including abdominal obesity, insulin resistance, hypertension, and dyslipidaemia. People with MetS may have a higher risk of coronary heart disease and stroke than those without MetS. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have cardioprotective, anti-inflammatory, and triglyceride-lowering properties, so they may help treat obesity and improve metabolic syndrome. The aim of this study was to explore the effects of n-3 PUFAs on lipid profile and blood pressure in patients with MetS. This study is a meta-analysis of eight studies. One of the studies was a crossover trial, whereas the remaining seven studies were parallel-controlled trials. The mean age of the participants was 45.54 years old. Results show that following supplementation with n-3 PUFAs in patients with metabolic syndrome: - there weren’t significant changes in serum total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. - there was a significant reduction in serum triglycerides and blood pressure. Authors conclude that n-3 PUFA supplementation may serve as a potential dietary supplement for improving lipids and blood pressure in patients with metabolic syndrome.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Omega 3 PUFA may be beneficial for patients with metabolic syndrome by improving serum lipid profile and blood pressure.
- Omega-3 rich foods include fatty fish, walnuts, flaxseeds and chia seeds.
- While Omega-3 PUFA may be beneficial, they should be considered as part of a comprehensive approach to managing metabolic syndrome that include physical activity and a balanced diet.
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:
Background
This journal article presents a systematic review and meta-analysis of randomised controlled trials (RCTs) investigating the effects of omega-3 fatty acid supplementation on serum lipid profile and blood pressure in patients with metabolic syndrome. Metabolic syndrome is a cluster of conditions that increase the risk of cardiovascular disease and type 2 diabetes.
Methods
This meta-analysis included 8 RCTs with 387 participants with metabolic syndrome. Participants in the intervention group took omega-3 fatty acid supplements and the outcomes included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), systolic blood pressure (SBP), and diastolic blood pressure (DBP).
Results
- Based on a meta-analysis of data from the included trials, supplementation with omega 3- PUFAs led to no reduction in serum LDL-c level among patients with metabolic syndrome (Standardised Mean Difference (SMD) = 0.18; 95% CI: −0.18 ~ 0.53, I2 = 55%); did not increase serum high-density lipoprotein cholesterol levels (SMD = 0.02; 95% CI: −0.21 ~ 0.25, I2 = 0%); and had no reduction in serum total cholesterol level (SMD = −0.02; 95% CI: −0.22~0.18, I2 = 24%).
- On the other hand, in patients with metabolic syndrome, supplementation with omega 3- PUFAs may decrease serum triglyceride levels (SMD = −0.39; 95% CI: −0.59 ~ −0.18, I2 = 17.2%); systolic blood pressure (SMD = −0.54; 95% CI: −0.86 ~ −0.22, I2 = 48.6%); and diastolic blood pressure (SMD = −0.56; 95% CI: −0.79~ −0.33, I2 = 14.0%).
- Sensitivity analyses indicated that the pooled estimates wererobust for all outcomes.
- The following mechanisms may explain how PUFAs may reduce the risk of metabolic syndrome. First, adequate intake of omega 3 PUFAs may reduce triglyceride and LDL synthesis in the liver. In addition, they may lower blood pressure by reducing angiotensin-converting enzyme levels in the aorta. Finally, PUFAs can increase insulin sensitivity and prevent hyperglycaemia.
Limitations
This study presents some limitations: The literature search may have some omissions. The conclusions may be hindered by the risk of bias of the trials included. No bias test was performed due to the limited number of studies.
Clinical practice applications:
- Improved serum lipid profile: The findings from the paper indicate that omega-3 fatty acid supplementation can have a positive impact on the serum lipid profile in patients with metabolic syndrome.
- Blood pressure management: omega-3 fatty acid supplementation may help reduce blood pressure in patients with metabolic syndrome.
- Nutritional therapists can use this information to consider omega-3 supplementation as part of nutritional therapy
- Complementary approach: Nutritional therapists can utilise the findings as supportive evidence for a holistic approach to managing metabolic syndrome. By incorporating omega-3 fatty acids into personalized nutrition plans, therapists may be able to offer additional dietary or supplemental interventions for individuals with metabolic syndrome, aiming to lower triglyceride levels and manage blood pressure, alongside other lifestyle modifications.
- Patient education: Nutritional therapists can educate their patients with metabolic syndrome about the benefits of omega-3 fatty acids on lipid profile and blood pressure. By explaining the findings from the systematic review and meta-analysis, therapists can empower patients to make informed choices regarding their dietary habits and supplement use, promoting self-management and improved long-term outcomes.
Considerations for future research:
- Future research could focus on determining the optimum dosage of Omega-3 PUFAs for improving lipid profile and BP.
- More investigation is needed to analyse the long term effect of the supplements. The longest RCT was 90 days.
- Comparative studies comparing the effects of omega-3 fatty acids supplementation with other interventions commonly used in metabolic syndrome management, such as pharmacological approaches or diet, would provide a comprehensive understanding of their relative effectiveness.
- Future research could explore potential variations in the effects of omega-3 fatty acids supplementation based on different patient characteristics, such as age, gender, baseline lipid profile, and blood pressure levels.
- Conducting mechanistic studies could shed light on the underlying pathways through which omega-3 fatty acids exert their effects on serum lipid profile and blood pressure.
Abstract
The purpose of this study was to explore the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation on serum lipid profile and blood pressure in patients with metabolic syndrome. We searched PubMed, Web of Science, Embase, and the Cochrane library from database inception to 30 April 2022. This meta-analysis included eight trials with 387 participants. We found that supplementation of n-3 PUFAs has no significant reduction in TC level (SMD = -0.02; 95% CI: -0.22 ~ 0.18, I2 = 23.7%) and LDL-c level in serum (SMD = 0.18; 95% CI: -0.18 ~ 0.53, I2 = 54.9%) of patients with metabolic syndrome. Moreover, we found no significant increase in serum high-density lipoprotein cholesterol level (SMD = 0.02; 95% CI: -0.21 ~ 0.25, I2 = 0%) in patients with metabolic syndrome after consuming n-3 PUFAs. In addition, we found that n-3 PUFAs can significantly decrease serum triglyceride levels (SMD= -0.39; 95% CI: -0.59 ~ -0.18, I2 = 17.2%), systolic blood pressure (SMD = -0.54; 95% CI: -0.86 ~ -0.22, I2 = 48.6%), and diastolic blood pressure (SMD = -0.56; 95% CI: -0.79 ~ 0.33, I2 = 14.0%) in patients with metabolic syndrome. The results from the sensitivity analysis confirmed that our results were robust. These findings suggest that n-3 PUFA supplementation may serve as a potential dietary supplement for improving lipids and blood pressure in metabolic syndrome. Given the quality of the included studies, further studies are still needed to verify our findings.
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4.
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
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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:
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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:
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.
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5.
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
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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:
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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:
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.
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6.
The Gut Microbiome in Early Life Stress: A Systematic Review.
Agusti, A, Lamers, F, Tamayo, M, Benito-Amat, C, Molina-Mendoza, GV, Penninx, BWJH, Sanz, Y
Nutrients. 2023;15(11)
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Children exposed to early life stress (ELS) show alterations in brain development and are at increased risk of developing mental illness. This study aims to clarify whether ELS influences the gut microbiome and whether this can be a predictor for the development of mental disorders. 13 articles were included in this systemic review. 4 looked at pre-natal stress and 9 at post-natal stress. Prenatal stress (via maternal stress) may be associated with an increase in Proteobacteria phylum and with a lower abundance of Bifidobacterium and lactic acid bacteria. In the postnatal group, greater microbiome diversity was related to lower depression and anxiety. In boys scores for adaptive skills were higher in those with good levels of Bifidobacterium. A positive association was found between EA (early adversity) experiences and gastrointestinal symptoms and anxiety. This review demonstrates links between ELS and gut microbiome changes. Further research will be necessary to draw more robust conclusions.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This systematic review consolidated and discussed existing evidence on the link between early life stress (ELS) and changes to the human microbiome
- Exposure to ELS, prenatal or postnatal during childhood and adolescence, may impact mental and physical health.
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 systematic review was conducted to consolidate clinical evidence examining the impact of early life stress (ELS) on the human intestinal microbiome.
Method
Thirteen observational studies were included in the review, sourced from Pubmed, Scopus, Web of Science, and EMBASE. Methodological quality was assessed using the Newcastle-Ottawa Assessment Scale (NOS), with most studies scoring seven or eight out of nine stars.
Study designs varied, including prospective prenatal studies, postnatal longitudinal studies, case-control studies, and cross-sectional studies. Four prenatal studies were prospective in design. The other nine postnatal studies included one longitudinal study, five case-control studies, and three cross-sectional studies. All 13 studies were published between 2015 and 2022. Because study designs and outcome assessments varied, the results were presented in a narrative form. Data was extracted by 2 independent authors.
Results
The primary findings from the review were as follows:
- Four longitudinal stress studies indicated that pregnant mothers experiencing psychological stress, increased cortisol levels, HIV, and lack of social support exhibited a lower abundance of beneficial Bifidobacterium and an increased abundance of Enterobacter genus.
- One postnatal stress longitudinal study (n=260) demonstrated lower depression and anxiety and improved internalising behaviour in patients with high microbiome diversity.
- . One postnatal stress case-control study (n=344) showed changes in the microbiome and an abundance of several bacterial taxa in stressed groups, including genera Prevotella, Bacteroides (Bacteroidetes), Coprococcus, Streptococcus, and Escherichia.
- One cross-sectional study of 128 adults without psychiatric conditions revealed that higher stress correlated with increased levels of Bacteroides, Parabacteroides, Rhodococcus, Methanobrevibacter, and Roseburia at the genus level, as well as lower Phascolarcto bacterium and Firmicutes at the phylum level.
- One large prospective study (n=446) found infants exposed to higher cumulative stress exhibited an increased relative abundance of Proteobacteria groups and lower Bifidobacterium.
Conclusion:
Due to the inconsistency of study designs and their results this review failed to find consensus microbiome signatures associated with pre- or postnatal stress, or both.
Clinical practice applications:
- Early life stress, and alterations in the gut microbiome, have been linked to mental health conditions
- Maternal prenatal stress may be linked to emotional, behavioural, and cognitive outcomes in infants.
Considerations for future research:
- Future research should standardise questionnaires, to ensure consistency and comparability across studies
- Additionally, future studies should consider using standard procedures and specific species and strain resolution shotgun metagenomics sequencing
- Consideration should be given to the influence of environmental variables (diet, physical activity, etc.) and sex in gut microbiome analysis.
Abstract
Exposure to early life stress (ELS), prenatal or postnatal during childhood and adolescence, can significantly impact mental and physical health. The role of the intestinal microbiome in human health, and particularly mental health, is becoming increasingly evident. This systematic review aims to summarize the clinical data evaluating the effect of ELS on the human intestinal microbiome. The systematic review (CRD42022351092) was performed following PRISMA guidelines, with ELS considered as exposure to psychological stressors prenatally and during early life (childhood and adolescence). Thirteen articles met all inclusion criteria, and all studies reviewed found a link between ELS and the gut microbiome in both prenatal and postnatal periods. However, we failed to find consensus microbiome signatures associated with pre- or postnatal stress, or both. The inconsistency of results is likely attributed to various factors such as different experimental designs, ages examined, questionnaires, timing of sample collection and analysis methods, small population sizes, and the type of stressors. Additional studies using similar stressors and validated stress measures, as well as higher-resolution microbiome analytical approaches, are needed to draw definitive conclusions about the links between stress and the human gut microbiome.
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7.
The Efficacy of Self-Management Strategies for Females with Endometriosis: a Systematic Review.
Mardon, AK, Leake, HB, Hayles, C, Henry, ML, Neumann, PB, Moseley, GL, Chalmers, KJ
Reproductive sciences (Thousand Oaks, Calif.). 2023;30(2):390-407
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Endometriosis is a gynaecological condition with symptoms of pelvic pain, fatigue, and stress. Decreased quality of life, impaired fertility and hinderances to carry out day to day tasks are all associated with endometriosis. Treatment options involve medications and surgery; however, both are associated with poorer outcomes than the initial disease itself. Self-management strategies that the individual can perform themselves, such as lifestyle changes, meditation, and rest have all been used to improve the quality of life of individuals with endometriosis, however their effectiveness has not been determined. This systematic review and meta-analysis aimed to determine the effectiveness of self-management strategies for the management of endometriosis. The study showed that many self-management strategies were no more effective than placebo or hormonal therapies for the management of endometriosis. It was concluded that many self-management strategies were no more effective than hormonal treatment at reducing endometriosis symptoms and the studies that did show a benefit were insufficient to base recommendations on due to poor design. This study could be used by healthcare professionals to understand that currently the research on self-management strategies of endometriosis is poor and whilst some may be of benefit to individuals who cannot or do not want to take hormone therapy, more research is warranted.
Expert Review
Conflicts of interest:
None
Take Home Message:
It is not possible to generalise the findings of this systematic review for the self-management of endometriosis due to the poor quality of evidence. Further studies of higher quality are needed.
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
Endometriosis is an inflammatory condition where endometrial-like tissue is found outside of the uterus. Diagnosis of endometriosis is made in around 6-10% of females of reproductive age. Endometriosis can adversely affect fertility, psychological well being and quality of life (QoL). Conventional interventions can have side effects and limited effectiveness. The aim of this systematic review (SR) was to evaluate the efficacy of self-management interventions for pain-related symptoms and QoL.
Methods
Fifteen experimental studies were included in this SR. Ten evaluated dietary supplements, three evaluated dietary modifications, one evaluated over-the-counter (OTC) medication, and one evaluated exercise. Outcome measures were self-reported for dysmenorrhoea, dyspareunia, overall pain, non-menstrual pelvic pain, use of medications and QoL.
Results
- Most dietary supplements were no more effective than placebo or frequently recommended medical interventions, at reducing pain-related outcomes.
- Melatonin (one RCT n=30) performed better than placebo for managing dysmenorrhoea and overall pain but not for non-menstrual pelvic pain. PEA-transploydatin (one RCT n=20) performed better than placebo for dysmenorrhoea and non-menstrual pelvic pain but not better than medical intervention.
- Resveratrol (one RCT n=22 & one intervention study n=12) plus the oral contraceptive pill (OCP) was more effective than the OCP alone for managing dysmenorrhoea.
- In one observational study, 75% of participants (n=295) reported a reduction in ‘high’ intensity pain scores following a 12-month gluten-free diet (p- value =<0.005). Similarly, a full dietary modification (one non randomised controlled trial , n=30) found less participants reporting pain at ‘high intensity’ (18%) compared to linseed and calcium oil supplements (41%) and placebo (62%).
- A metal trace element supplement was more effective than placebo for managing overall pain (one RCT p- value<0.001).
- Naproxen (one cross over trial, n=11) performed better than placebo at managing dysmenorrhoea (83% vs 41%, p- value 0.008).
- Hatha yoga (one RCT n=12) was found to be effective at reducing overall pain and improving QoL compared to no yoga (p-value <0.05).
Conclusion
Due to limited, low-quality evidence, high risk of bias and high levels of heterogeneity between studies, it was not possible to generalise the findings of the studies included in this systematic review. Further research of high-quality is needed in order to make self-management recommendations for females with endometriosis.
Notes: The authors reported no conflicts of interest.
Clinical practice applications:
Evidence-based self-management interventions are considered critical for the management of endometriosis. However, the quality of evidence in this SR was considered of poor quality. Further high-quality research is needed in order to be able to make recommendations. Strategies that showed potential benefits included:
- Dietary modifications and a gluten-free diet may be effective for reducing the intensity of pain associated with endometriosis.
- Hatha yoga may be effective at reducing overall pain and supporting psychological wellbeing and QoL.
Considerations for future research:
High quality studies are needed as well as a ‘gold standard’ definition for self-management criteria. Understanding potential barriers to self-management interventions may also be beneficial.
Abstract
Self-management is critical for the care of endometriosis. Females with endometriosis frequently use self-management strategies to manage associated symptoms; however, the efficacy of such strategies is unknown. The aim of this review was to systematically appraise the evidence concerning efficacy of self-management strategies for endometriosis symptoms. Electronic databases, including Medline, Embase, Emcare, Web of Science Core Collection, Scopus, and the Cochrane Central Register of Controlled Trials, were searched from inception to March 2021. We included peer-reviewed experimental studies published in English evaluating the efficacy of self-management strategies in human females laparoscopically diagnosed with endometriosis. Studies underwent screening, data extraction, and risk of bias appraisal (randomised studies: Risk of Bias 2 tool; non-randomised studies: Risk Of Bias In Non-randomized Studies - of Interventions tool). Of the fifteen studies included, 10 evaluated dietary supplements, three evaluated dietary modifications, one evaluated over-the-counter medication, and one evaluated exercise. Most studies had a high-critical risk of bias. Many self-management strategies were not more effective at reducing endometriosis symptoms compared to placebo or hormonal therapies. Where studies suggest efficacy for self-management strategies, no recommendations can be made due to the poor quality and heterogeneity of evidence. High-quality empirical evidence is required to investigate the efficacy of self-management strategies for females with endometriosis.
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8.
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
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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:
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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 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.
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9.
Mediterranean diet and structural neuroimaging biomarkers of Alzheimer's and cerebrovascular disease: A systematic review.
Gregory, S, Pullen, H, Ritchie, CW, Shannon, OM, Stevenson, EJ, Muniz-Terrera, G
Experimental gerontology. 2023;172:112065
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Nearly a million people in the UK have Alzheimer's disease, the most common type of dementia. Mediterranean diet (MedDiet) adherence is associated with healthy brain ageing, a reduced stroke risk, and a lower incidence of dementia. Seven studies were included in this review to evaluate the effects of MedDiet on hippocampal volume and white matter hyperintensity volume, predictors of stroke and dementia. This systematic review did not reveal any associations between MedDiet adherence and hippocampal volume. However, there was a significant negative relationship between MedDiet adherence and white matter hyperintensity volume in two of the studies included. It is necessary to conduct more robust studies to investigate the associations between MedDiet adherence and structural brain imaging findings and understand the mechanisms behind dementia and other cerebrovascular diseases. This study could provide healthcare professionals with valuable information about the effects of increased MedDiet adherence on brain health, including its potential to delay neurodegenerative disease progression.
Expert Review
Conflicts of interest:
None
Take Home Message:
Due to inconclusive results on the associations between MedDiet adherence and AD and cerebrovascular related structural neuroimaging findings, specific recommendations for the MedDiet cannot be made on the basis of this study until further research has been completed.
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:
Background:
Changes in hippocampal volume (HV) and white matter intensity volume (WMIV) have been identified as structural neuroimaging biomarkers of neurodegenerative disease such as Alzheimer’s Disease (AD) and Cerebrovascular disease (CVD) respectively. Evidence has shown adherence to the Mediterranean Diet (MedDiet) has been associated with reduced risk for strokes. This review evaluated the MedDiet in relation to HV and WMIV.
Methods:
The review followed PRISMA guidelines and was registered on PROSPERO. Literature searching resulted in seven studies published between 2012 and 2022, which met the inclusion criteria. Six studies analysed cross-sectional data and one analysed longitudinal data. The NIH Quality Assessment Tool for Observational and Cross-Sectional Studies was used to assess risk of bias.
Overall, the studies were rated as low-risk of bias with details of the research question, participant group exposure and outcome variables included. Due to moderate to high heterogeneity in some studies, a meta-analysis was deemed unsuitable and narrative synthesis was conducted to present the results.
Results:
Mean participant age ranged from 53.19 to 80.3 years and volunteers were healthy or had subjective cognitive decline and a few participants had dementia (n=46).
Hippocampal Volume:
Four studies included 20,077 participants and found no significant associations between MedDiet adherence and hippocampal volume. All four studies were cross-sectional from larger cohort studies. To establish causative relationships longitudinal and RCT trials are required.
White Matter Hyperintensity Volumes:
Four studies included 1938 participants. Two studies found a significant negative association between MedDiet and WMHV, demonstrating higher Mediterranean Scores were associated with lower level of WHMV. The other two studies found no significant associations.
Although the review methodology with a piloted search strategy was considered a key strength, the lack of meta-analysis as planned in the a priori protocol, due to minimal eligible studies and high heterogeneity was a limitation as well as the restriction of brain imaging outcomes.
Conclusion:
Overall, these results are inconclusive on the associations between the MedDiet and HV and WMHV, and identify a gap in the knowledge, therefore further research such as RCT’s remains a priority to further understand the impact diet may have on neuroimaging markers of AD and CVD.
Clinical practice applications:
There were no significant associations between MedDiet adherence and HV, which was surprising given the evidence stating adherence to the MedDiet is associated with a lower incidence of dementia and stroke. However all four studies were cross-sectional studies and in order to detect causal associations, longitudinal and RCT’s are needed. Two studies did show a significant association between higher MedDiet adherence and lower WMHV, whereas two studies reported no significant associations.
Caution needs to be taken when recommending the MedDiet specifically for a reduction in HV and WMHV until further research has been undertaken.
Considerations for future research:
Future research should consider:
- larger cohorts and participants from the Mediterranean region where lifelong adherence to the MedDiet is more likely.
- looking at other risk factors to include obesity, lack of activity, poor sleep quality and stress.
- evaluating different socio-economic status, which has been shown to impact dietary behaviour.
- alternative imaging outcomes such as cortical thinning, PET amyloid and tau.
- . gold standard for methodology in particular dietary analysis and scanning and outcome derivation.
Abstract
Previous studies have demonstrated an association between adherence to the Mediterranean diet (MedDiet) and better cognitive performance, lower incidence of dementia and lower Alzheimer's disease biomarker burden. The aim of this systematic review was to evaluate the evidence base for MedDiet associations with hippocampal volume and white matter hyperintensity volume (WMHV). We searched systematically for studies reporting on MedDiet and hippocampal volume or WMHV in MedLine, EMBASE, CINAHL and PsycInfo. Searches were initially carried out on 21st July 2021 with final searches run on 23rd November 2022. Risk of bias was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Of an initial 112 papers identified, seven papers were eligible for inclusion in the review reporting on 21,933 participants. Four studies reported on hippocampal volume, with inconclusive or no associations seen with MedDiet adherence. Two studies found a significant association between higher MedDiet adherence and lower WMHV, while two other studies found no significant associations. Overall these results highlight a gap in our knowledge about the associations between the MedDiet and AD and cerebrovascular related structural neuroimaging findings.
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10.
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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Plain language summary
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).