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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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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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3.
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
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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:
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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
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.
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Adherence to a Mediterranean Diet for 6 Months Improves the Dietary Inflammatory Index in a Western Population: Results from the MedLey Study.
Clark, JS, Dyer, KA, Davis, CR, Shivappa, N, Hébert, JR, Woodman, R, Hodgson, JM, Murphy, KJ
Nutrients. 2023;15(2)
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Chronic inflammation is thought to be an underlying cause of many chronic diseases and diet can be used to modulate inflammation. The dietary inflammatory index (DII) is a tool rating an individual’s diet as pro- or anti-inflammatory, with an anti-inflammatory diet (low DII) being associated with a reduced risk of cardiometabolic disease. The aim of this 6-month randomised controlled trial was to evaluate the effect of a Mediterranean diet (MedD), as compared to a typical Australian diet (AusD), on DII and cardiometabolic risk factors in healthy Australians aged 65 years or older. Participants on the MedD significantly decreased their DII and had reductions in F2-Isoprostanes (marker of oxidative stress), triglycerides and systolic BP at 3 months and 6 months as well as improved endothelial function at 6 months. However, changes in DII did not correlate with changes in cardiometabolic risk factors. Evaluation of baseline parameters of both groups combined showed associations of DII with BMI, weight, abdominal fat, HDL and systolic blood pressure, with a lower DII correlating with lower risks. The authors concluded that a MedD decreases the DII which may help reduce the risk of cardiovascular disease.
Expert Review
Conflicts of interest:
None
Take Home Message:
- When individuals follow The Mediterranean Diet they are able to reduce their dietary inflammation score.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
- Chronic inflammation is thought to be an underlying cause of many chronic diseases.
- The dietary inflammatory index (DII) is a tool for rating an individual’s diet as pro- or anti-inflammatory. A low DII (anti-inflammatory diet) is associated with reductions in cardiometabolic diseases.
- The aim of the study was to evaluate the effect of a dietary intervention (Mediterranean diet) on DII and cardiometabolic risk factors in older Australians.
Methods
- Randomised controlled trial.
- Duration: 6 months.
- Participants: 152 healthy Australian men and women aged 65 years or older.
- Intervention: Traditional Mediterranean diet (MedD, fortnightly sessions with dietician); control: Habitual Australian diet (AusD)
- Outcome measures: DII and energy-adjusted DII (E-DII), blood pressure (BP), anthropometric parameters, endothelial function (measured as flow mediated dilatation, FMD), F2-isoprostanes (F2-IsoP, marker of oxidative stress), inflammatory biomarkers, lipids, glucose, insulin, dietary compliance, cognitive performance.
Results
- Over the 4 months, the E-DII decreased by 1.1 points in the MedD group (<0.001), but did not decrease in the AusD group (p=0.21).
- Compared to AusD, participants on MedD had reductions in F2-IsoP, triglycerides and systolic BP at 3 months and 6 months; improved endothelial function at 6 months (no p-values given as reported elsewhere).
- No associations between changes in DII and changes in cardiometabolic outcomes, independent of whether participants were normal or overweight.
- Baseline E-DII scores of both groups combined were divided into tertiles and associations with cardiometabolic parameters evaluated (p-values refer to highest vs lowest tertile):
- Higher E-DII was associated with higher BMI (p=0.04); body weight (p<0.0001); hip-to-waist ratio (p=0.001) and abdominal fat (p=0.03).
- Lower E-DII was associated with higher HDL cholesterol (p=0.04) and lower systolic BP (p=0.005).
- No associations between E-DII and other outcome measures.
Conclusion
- The authors concluded that adherence to a MedD reduces dietary inflammation index scores, which may be beneficial for reducing chronic disease risk.
Clinical practice applications:
- The Mediterranean diet lowers dietary inflammatory index scores. This may, in turn, help reduce risk of cardiometabolic disease.
Considerations for future research:
- Larger and longer-term trials may confirm whether or not the reduction of DII with a MedD translates into a reduction in measurable inflammation and cardiovascular disease.
Abstract
Increasing evidence supports that a higher dietary inflammatory index (DII®) score is associated with inflammation and cardiovascular disease (CVD) risk, events, and mortality. This randomized trial sought to determine if a change to a Mediterranean diet resulted in a reduction in the DII score, and then it evaluated the relationship between the DII and cardiometabolic outcomes following the administration of a traditional Mediterranean diet in older Australian adults. A total of 152 Australian adults (mean age 71 ± 5 years) was randomly allocated either a MedDiet (n = 80) or to continue their habitual diet (HabDiet) (n = 72) for 6 months. Diet and cardiovascular outcomes were measured at baseline and 3 and 6 months of the intervention. DII and energy-adjusted DII (E-DIITM) scores were calculated from 3-day weighed food records. There was a significant reduction in the DII score at 2 and 4 months for the MedDiet group (−1.40 ± 0.20 p < 0.001 and −1.47 ± 0.20 p < 0.001, respectively), which was significantly different from the HabDiet group over time (p < 0.001). The HabDiet DII score did not change significantly at the 2 and 4 months timepoints (0.47 ± 0.21 p = 0.35 and 0.54 ± 0.21 p = 0.21, respectively). The improvement in the DII in the MedDiet group was not related to any cardiometabolic outcome. Baseline cross-sectional analyses identified a positive association between the E-DII score and average BMI, body weight, WHR, abdominal adiposity, and SBP, and a negative association with HDL-C. We demonstrate that a MedDiet intervention significantly reduced DII scores compared with a habitual Australian diet in older Australians. This could be beneficial for healthy ageing and the avoidance of chronic disease in Western populations.
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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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6.
Effects of Diet on 10-Year Atherosclerotic Cardiovascular Disease Risk (from the DASH Trial).
Jeong, SY, Wee, CC, Kovell, LC, Plante, TB, Miller, ER, Appel, LJ, Mukamal, KJ, Juraschek, SP
The American journal of cardiology. 2023;187:10-17
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Determining the 10-year risk of heart disease can be used as tool to determine appropriate treatment plans. This study of 459 adults aged 22-75 years with obesity aimed to compare the effects on the 10-year risk for the development heart disease of an 8-week dietary approaches to stop hypertension (DASH) diet, with the standard American diet (AD) and a diet high in fruits and vegetables (F/V). The results showed that the DASH diet significantly improved risk factors such as systolic blood pressure and total cholesterol. However, the F/V diet had an improvement in good cholesterol, which the DASH diet did not. This equated to a similar 10% reduction in the 10-year heart disease risk compared to the AD. It was concluded that compared to a typical AD, DASH and F/V diets reduced the risk for heart disease over a 10-year period. However, the actual risk reduction was only small and individuals with obesity may need to reduce their risk further with other therapies. This study could be used by healthcare professionals to recommend a DASH diet or a diet high in fruits and vegetables to reduce the long-term risk for heart disease alongside other proven therapies or methods to reduce risk.
Expert Review
Conflicts of interest:
None
Take Home Message:
- DASH and F/V diets may be of benefit to obese individuals to decrease their risk for ASCVD
- The DASH diet did reduce HDL cholesterol and recommendations should be made to limit this effect (e.g. exercise and more fruit and vegetables in the 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:
Introduction
This study aimed to determine the effect of the Dietary Approaches to Stop Hypertension (DASH) diet compared to a standard American diet (AD) and a diet emphasising fruits and vegetables (F/V) on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) and how adopting these diets affect specific risk factors (e.g systolic blood pressure (SBP), diastolic blood pressure (DBP) and blood lipids).
Methods
- Secondary analysis from the DASH trial which ran for 8 weeks in 459 adults aged 22-75 years with obesity
- All meals were provided and dietary intake was adjusted to prevent weight loss
- The primary outcome was an absolute and relative difference in 10-year ASCVD risk from baseline.
Participants were randomised to one of three diets:
1) DASH diet
2) F/V diet, similar to AD but with more fruits and vegetables and higher potassium and magnesium
3) Standard AD.
Results
- DASH significantly lowered SBP, total cholesterol, and HDL cholesterol compared to F/V (absolute difference SBP: -2.8, (95% confidence interval [CI]-4.5, -1.2), total cholesterol: 9.3 (-14.7, 3.9), and HDL cholesterol: -3.5 (-5.0, -2.1) P=<0.05 for all)
- DASH significantly lowered SBP, total cholesterol, and HDL cholesterol compared to AD (absolute difference SBP: -5.3 (-7.0, -3.7), total cholesterol: -13.1 (-18.5, -7.7), and HDL cholesterol: -3.8 (-5.2, -2.4) P=<0.05 for all)
- Compared to AD, DASH and F/V diets reduced 10-year ASCVD relative risk by -10.3%
( −14.4 to −5.9) and −9.9% ( −14.0 to −5.5) respectively
- This translated into low actual risk reductions of -0.21% for the F/V diet and -0.17% for the DASH diet
- Although DASH improved SBP, and total cholesterol compared to F/V, no differences in ASCVD risk between DASH and F/V were apparent. This was attributable to the detrimental effect of the DASH diet on HDL cholesterol, which was not seen in the F/V diet
- The effects of the DASH diet were more pronounced in black participants and in women.
Conclusion
Compared to the AD, DASH and F/V reduced 10-year ASCVD risk by approximately 10% over 8-weeks. The DASH diet was more effective for women and black adults.
Clinical practice applications:
- DASH and F/V diets decrease risk factors and an individual’s risk of ASCVD, and should be encouraged in individuals with obesity, especially women and black adults
- However, these diets do still leave obese individuals at risk for ASCVD.
Considerations for future research:
- Research on these diets in combination with weight loss regimes may give more pronounced results
- It may also be interesting to understand the mechanisms behind why the DASH diet reduces HDL cholesterol.
Abstract
Although modern risk estimators, such as the American College of Cardiology/American Heart Association Pooled Cohort Equation, play a central role in the decisions of patients to start pharmacologic therapy to prevent atherosclerotic cardiovascular disease (ASCVD), there is limited evidence to inform expectations for 10-year ASCVD risk reduction from established lifestyle interventions. Using data from the original DASH (Dietary Approaches to Stop Hypertension) trial, we determined the effects of adopting the DASH diet on 10-year ASCVD risk compared with adopting a control or a fruits and vegetables (F/V) diet. The DASH trial included 459 adults aged 22 to 75 years without CVD and not taking antihypertensive or diabetes mellitus medications, who were randomized to controlled feeding of a control diet, an F/V diet, or the DASH diet for 8 weeks. We determined 10-year ASCVD risk with the American College of Cardiology/American Heart Association Pooled Cohort Equation based on blood pressure and lipids measured before and after the 8-week intervention. Compared with the control diet, the DASH and F/V diets changed 10-year ASCVD risk by -10.3% (95% confidence interval [CI] -14.4 to -5.9) and -9.9% (95% CI -14.0 to -5.5) respectively; these effects were more pronounced in women and Black adults. There was no difference between the DASH and F/V diets (-0.4%, 95% CI -6.9 to 6.5). ASCVD reductions attributable to the difference in systolic blood pressure alone were -14.6% (-17.3 to -11.7) with the DASH diet and -7.9% (-10.9 to -4.8) with the F/V diet, a net relative advantage of 7.2% greater relative reduction from DASH compared with F/V. This was offset by the effects on high-density lipoprotein of the DASH diet, which increased 10-year ASCVD by 8.8% (5.5 to 12.3) compared with the more neutral effect of the F/V diet of -1.9% (-5.0 to 1.2). In conclusion, compared with a typical American diet, the DASH and F/V diets reduced 10-year ASCVD risk scores by about 10% over 8 weeks. These findings are informative for counseling patients on both choices of diet and expectations for 10-year ASCVD risk reduction.
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7.
An Energy-Reduced Mediterranean Diet, Physical Activity, and Body Composition: An Interim Subgroup Analysis of the PREDIMED-Plus Randomized Clinical Trial.
Konieczna, J, Ruiz-Canela, M, Galmes-Panades, AM, Abete, I, Babio, N, Fiol, M, Martín-Sánchez, V, Estruch, R, Vidal, J, Buil-Cosiales, P, et al
JAMA network open. 2023;6(10):e2337994
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The Mediterranean diet (MedDiet), which focuses on whole grains, lean meat, fruits, vegetables, and low amounts of minimally processed foods has been shown in previous research to improve body composition and decrease fat storage around the middle. This randomised control trial of 1556 older adults aimed to determine the effects of combining a 30% lower energy version of the MedDiet in combination with physical exercise on body composition. After 3 years, the results showed that compared to a normal MedDiet without exercise, the lower energy version in combination with exercise improved body composition by decreasing total fat, and the fat stored around the organs and increasing muscle mass. However, benefits were more pronounced after 1 year and decreased slightly at 3 years. It was concluded that a low energy MedDiet in combination with physical activity may be able to improve the body composition of overweight and older adults with obesity. This study could be used by healthcare professionals to recommend a low energy MedDiet to older adults to promote weight loss, whilst attenuating muscle loss associated with ageing.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The addition of exercise to an energy-reduced diet, which focuses on whole grains, healthy fats, lean protein, and fruits and vegetables can emphasise positive effects on body composition in older adults.
- However, there is a loss of lean mass associated with this type of diet (contrary to author conclusions) and measures should be taken to monitor and increase protein intake to prevent or limit this loss.
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 study aimed to determine the long-term effects of an energy reduced MedDiet in combination with physical activity on body composition.
Methods
- This is a predetermined 3-year interim analysis of a 6-year single-blind, randomised control trial of 1556 individuals aged 55-75 who are overweight or obese with metabolic syndrome.
- 760 individuals on 30% energy reduced MedDiet with limited processed foods, plus 45 minutes walking 6 days per week and behavioural and motivational support. [Intervention group]
- 761 on standard MedDiet without physical activity. [Control]
Results
Within group comparisons showed that individuals in the intervention group lost (P value represents baseline vs year 3):
- Total fat mass percentage (1-year vs baseline, −1.14%; 95% CI, −1.32% to −0.96%; 3-year vs baseline, −0.52%; 95% CI, −0.71% to −0.33% P=<0.001)
- Absolute visceral fat (1-year vs baseline, −154 g; 95% CI, −191 to −116 g; 3-year vs baseline, −75.1 g, 95% CI, −115 to −35.3 g P=<0.001)
- Absolute total fat after 1 year (mean change at 1 year vs baseline, −1677 g; 95% CI, −1930 to −1424 g) but regained some at year 3 (mean change at 3 years vs baseline, −1018 g; 95% CI, −1280 to −756 g P=<0.001)
- Absolute lean mass (mean change at 1 year vs baseline −300 g; 95% CI, −439 to −162 g) with further losses at year 3 (−626 g; 95% CI, −770 to −483 g P=0.001).
Within group comparisons also showed significantly increased:
- Total lean mass percentage, which was greater at year 1 than year 3 (1-year vs baseline, 1.07%; 95%CI, 0.90%-1.25%; 3-year vs baseline, 0.47%; 95% CI, 0.29%-0.65% P=<0.001).
As a result of total fat loss and some lean mass in the intervention group, the lean:fat mass ratio improved and was unchanged in the control group (between group differences (P=<0.001).
Compared to women, men may find the MedDiet + exercise more beneficial as it was shown that body composition changes were slightly more pronounced in men.
Conclusion
An energy-reduced MedDiet plus exercise emphasised positive changes to body composition compared to standard MedDiet in older adults who are overweight or have obesity.
Clinical practice applications:
- The recommendation of a reduced energy MedDiet in combination with physical activity to older people who are overweight or obese may improve body composition.
- Although lean mass loss slowed between years 1 and 3, other practices should be employed to attenuate the loss of lean mass associated with an energy-reduced MedDiet and ageing.
Considerations for future research:
- The research has not yet concluded but when it does, it will address the incidence of cardiovascular disease along with body composition changes.
- It will also look at long-term effects of the diet to determine longevity.
- Future research could focus on how to limit lean mass loss through the possibility of changing the type of exercise that accompanies the MedDiet.
Abstract
IMPORTANCE Strategies targeting body composition may help prevent chronic diseases in persons with excess weight, but randomized clinical trials evaluating lifestyle interventions have rarely reported effects on directly quantified body composition. OBJECTIVE To evaluate the effects of a lifestyle weight-loss intervention on changes in overall and regional body composition. DESIGN, SETTING, AND PARTICIPANTS The ongoing Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial is designed to test the effect of the intervention on cardiovascular disease prevention after 8 years of follow-up. The trial is being conducted in 23 Spanish research centers and includes men and women (age 55-75 years) with body mass index between 27 and 40 and metabolic syndrome. The trial reported herein is an interim subgroup analysis of the intermediate outcome body composition after 3-year follow-up, and data analysis was conducted from February 1 to November 30, 2022. Of 6874 total PREDIMED-Plus participants, a subsample of 1521 individuals, coming from centers with access to a dual energy x-ray absorptiometry device, underwent body composition measurements at 3 time points. INTERVENTION Participants were randomly allocated to a multifactorial intervention based on an energy-reduced Mediterranean diet (MedDiet) and increased physical activity (PA) or to a control group based on usual care, with advice to follow an ad libitum MedDiet, but no physical activity promotion. MAIN OUTCOMES AND MEASURES The outcomes (continuous) were 3-year changes in total fat and lean mass (expressed as percentages of body mass) and visceral fat (in grams), tested using multivariable linear mixed-effects models. Clinical relevance of changes in body components (dichotomous) was assessed based on 5% or more improvements in baseline values, using logistic regression. Main analyses were performed in the evaluable population (completers only) and in sensitivity analyses, multiple imputation was performed to include data of participants lost to follow-up (intention-to-treat analyses). RESULTS A total of 1521 individuals were included (mean [SD] age, 65.3 [5.0] years; 52.1% men). In comparison with the control group (n=761), participants in the intervention arm (n=760) showed greater reductions in the percentage of total fat (between group differences after 1-year, -0.94% [95% CI, -1.19 to -0.69]; 3 years, -0.38% [95% CI, -0.64 to -0.12] and visceral fat storage after 1 year, -126 g [95% CI, -179 to -73.3 g]; 3 years, -70.4 g [95% CI, -126 to -15.2 g] and greater increases in the percentage of total lean mass at 1 year, 0.88% [95% CI, 0.63%-1.12%]; 3-years 0.34% [95% CI, 0.09%-0.60%]). The intervention group was more likely to show improvements of 5% or more in baseline body components (absolute risk reduction after 1 year, 13% for total fat mass, 11% for total lean mass, and 14% for visceral fat mass; after 3-years: 6% for total fat mass, 6% for total lean mass, and 8% for visceral fat mass). The number of participants needed to treat was between 12 and 17 to attain at least 1 individual with possibly clinically meaningful improvements in body composition. CONCLUSIONS AND RELEVANCE The findings of this trial suggest a weight-loss lifestyle intervention based on an energy-reduced MedDiet and physical activity significantly reduced total and visceral fat and attenuated age-related losses of lean mass in older adults with overweight or obesity and metabolic syndrome. Continued follow-up is warranted to confirm the long-term consequences of these changes on cardiovascular clinical end points. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN89898870.
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8.
Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial.
Katayoshi, T, Uehata, S, Nakashima, N, Nakajo, T, Kitajima, N, Kageyama, M, Tsuji-Naito, K
Scientific reports. 2023;13(1):2786
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Nicotinamide adenine dinucleotide (NAD+) is a coenzyme that plays a crucial role in energy metabolism and different biological processes. Sirtuins (SIRT1) are NAD+-dependent deacetylases, an enzyme that plays a key role in enhancing metabolic efficiency. Nicotinamide mononucleotide (NMN) is a precursor to NAD+. NMN supplementation may help to reduce the risk of developing metabolic diseases and cardiovascular diseases. This randomised, double-blinded, and placebo-controlled, parallel trial investigated the effects of 12 weeks of 125 mg NMN supplementation on metabolic health parameters, including CVD risk factors, blood NAD+ metabolites level, and SIRT1 expression in middle-aged men and women. Serum nicotinamide was significantly higher and arterial stiffness was lower in the NMN test group of middle-aged men and women after 12 weeks of NMN supplementation. The results of the study indicate that the administration of 250mg of nicotinamide mononucleotide (NMN) daily for an extended period is considered safe and well-tolerated. Healthcare professionals can use this finding to understand the significant implications of the use of NMN as a potential therapeutic agent in individuals seeking to improve their metabolic and cardiovascular health. Further robust studies are required to evaluate the effects of NMN supplementation due to the limitations and high baseline variability between the participants of this study.
Expert Review
Conflicts of interest:
None
Take Home Message:
- As we age, NAM levels decline, which could have a negative effect on cardiovascular health.
- Middle-aged adults may like to consider NMN supplementation to improve NAM metabolism and arterial stiffness.
- However, without data on CVD events, it is difficult to determine actual risk reductions.
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
- Nicotinamide adenine dinucleotide (NAD+) is a coenzyme involved in metabolism. When we age, NAD+ levels decline resulting in poorer metabolism and age-related disease such as cardiovascular disease (CVD). Nicotinamide mononucleotide (NMN) is a precursor in the biosynthesis of NAD+.
- This double-blind, randomised control trial aimed to determine the effect of supplementing NMN on NAD+ levels, CVD risk factors and sirtuin 1 (SIRT1) expression, which relies on NAD+ for adequate functioning.
Methods
- 36 healthy male and female individuals aged between 40-65 years of age were assigned to either NMN (125mg/day) or placebo for 12 weeks.
- One capsule was taken twice per day after meals.
- Serum nicotinamide (NAM), NAD+, NMN, advanced glycation end products (AGES), 8-hydroxydeoxyguanosine (8-OHdG) and SIRT1 mRNA expression were measured.
- The condition of blood vessels (arterial stiffness) was also assessed using the ankle brachial index (ABI).
- In a sub-analysis, individuals with hypertension, above average body mass index (BMI), or blood glucose level were also assessed for blood vessel condition using the ABI.
Results
- The results showed that from baseline serum NAM decreased in the placebo group (P=0.014), whereas it increased in the NMN group (P=0.006). This resulted in an increase in the NMN group compared to placebo (P=0.037).
- Interestingly serum NAM was lower in the NMN group compared to placebo at baseline (P=0.001).
- There was no statistically significant difference in ABI with NMN supplementation.
- Amongst those with hypertension there was also no change in ABI. However, those with high BMI or blood glucose, there was an improvement in vascular condition compared to placebo (P=<0.007 and P=0.019 respectively).
- 8-OHdG, SIRT1 mRNA and AGEs remained unchanged by NMN supplementation
Conclusion
- NMN supplementation enhanced NAD+ metabolism in middle-aged adults.
- It also relieved arterial stiffness and reduced CVD risk factors.
Clinical practice applications:
- Apparently healthy middle-aged adults who would like to activate NAD metabolism and decrease their risk for CVD, should consider 12-week supplementation with NMN (125mg/day).
- ABI should be monitored to ensure desired effects.
- It is unclear as to the effects of NMN supplementation after 12-weeks.
Considerations for future research:
- Future research should consider longer supplementation duration and/or adding in a follow-up period to determine duration of effect.
- Different supplemental doses should also be researched to determine an optimal dose.
Abstract
Many animal studies have shown that oral administration of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) prevents the reduction of NAD+ levels in organs and tissues, helping alleviate aging-related diseases. However, there are very few clinical reports of NMN supplementation in humans. Thus, this study aimed to investigate the influence of a 12-week NMN oral supplementation on biochemical and metabolic health parameters. A 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 36 healthy middle-aged participants received one capsule of either 125 mg NMN or placebo twice a day. Among the NAD+ metabolites, the levels of nicotinamide in the serum were significantly higher in the NMN intake group than in the placebo group. Pulse wave velocity values indicating arterial stiffness tended to decrease in the NMN intake group. However, no significant difference was found between the two groups. Long-term NMN supplementation at 250 mg/day was well tolerated and did not cause adverse events. NMN safely and effectively elevated NAD+ metabolism in healthy middle-aged adults. Additionally, NMN supplementation showed potential in alleviating arterial stiffness.
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9.
Effect of Intermittent Fasting Diet on Glucose and Lipid Metabolism and Insulin Resistance in Patients with Impaired Glucose and Lipid Metabolism: A Systematic Review and Meta-Analysis.
Yuan, X, Wang, J, Yang, S, Gao, M, Cao, L, Li, X, Hong, D, Tian, S, Sun, C
International journal of endocrinology. 2022;2022:6999907
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The prevalence of obesity and metabolic syndrome may increase the risk of cardiovascular disease (CVD), diabetes, and neurological conditions. The imbalance in glucose and lipid metabolism and hypertension characterises the development of these chronic diseases. Intermittent fasting (IF) has been considered an effective dietary strategy for reducing the risk of obesity, insulin resistance, dyslipidaemia, diabetes, and CVD. This systematic review and meta-analysis include ten randomised controlled trials to evaluate the effects of IF intervention on glucose and lipid metabolism in people with metabolic syndrome. IF intervention regulated glucose metabolism by improving fasting blood glucose, glycosylated haemoglobin, insulin, and insulin resistance. IF intervention also positively impacted the body mass index and waist circumference. The total cholesterol, low-density lipoprotein levels, and triglyceride levels also improved, followed by the IF, showing the impact on lipid metabolism. Further robust studies are required due to heterogeneity between the included studies in type of IF, duration, the health status of participants, ethnicity, and outcome measurements. However, healthcare professionals can use the results of this systematic review and meta-analysis to understand the therapeutic effect of IF intervention on glycolipid metabolism in people with metabolic syndrome.
Expert Review
Conflicts of interest:
None
Take Home Message:
- IF does not require calorie restriction which may result in greater compliance
- IF does not restrict macronutrients such as CHO and fats, so may avoid the exclusion of key nutrients e.g. healthy fats and wholegrains.
- IF may have fewer adverse effects on daily routines and quality of life, which may mean adherence is easier.
- Improved glucose and lipid metabolism may prevent the development of chronic health conditions such as T2D, CVD and cancer.
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:
Management of glucose and lipid metabolism can be achieved through weight reduction using dietary interventions such as very low calorie or CHO diets, which may be effective but difficult to sustain long term. An alternative approach for weight management, improved insulin resistance and subsequent prevention of comorbitities e.g. Type 2 Diabetes (T2D), Cardiovascular Disease (CVD) and cancer, is Intermittent Fasting (IF). such as time restricted or periodic fasting.
This study summarises the effects of IF dietary interventions lasting less than three months in overweight and obese women with Metabolic Syndrome, defined as the presence of any metabolic dysfunction including obesity, hyperglycaemia, dyslipidaemia or hypertension.
The meta-anlaysis was carried out following PRISMA guidelines. A literature search in PubMed and Medline using the keywords obesity/overweight, IF diet, metabolic syndrome, RCT’s and humans resulted in 10 studies with 12 types of intervention for analysis. The following outcomes were evaluated: glucose and lipid metabolism, insulin resistance, weight loss and blood pressure.
Results were analysed in R software using mean differences and 95% confidence intervals, and either random or fixed effects depending on the Cochrane’s Q and I(2) statistics. Funnel plots were inspected for potential bias and Egger’s regression tests for publication bias.
There were significant differences before and after the interventions for all glucose and lipid metabolism markers as well as body weight and systolic blood pressure :
Glucose metabolism:
- Fasting glucose reduced by 0.15mmol/L
- Insulin plasma reduced by 13.25uUI
- HbA1c reduced by 0.08%
- HOMA-IR (insulin resistance index) reduced by 0.31 on average
Lipid metabolism:
- Total cholesterol reduced by 0.32mmol/L
- LDL reduced by 0.22mmol/L
- Triglyceride reduced by 0.04mmol/L
Weight loss:
- Body weight reduced by 1.87kg
- BMI reduced by 0.8kg/m2
- Waist circumference reduced by 2.08cm
Blood pressure:
- Systolic reduced by 2.58mmHg
- Diastolic reduced by 3.12mmHg
Despite limitations of the meta-analysis, this study demonstrates IF has therapeutic effects on those with disordered lipid and glucose metabolism, and may prove to be an effective and sustainable approach.
Clinical practice applications:
- IF may be an effective alternative to restricted calorie or CHO diets for weight management with the associated benefits of glucose and lipid metabolism.
- IF has been shown to have therapeutic effects on individuals with impaired glucose and lipid metabolism.
- IF may be considered as a sustainable lifestyle choice rather than a ‘weight loss’ programme such as a very low calorie diet, which can result in poor quality of life and subsequent reduced adherence.
- Since it may take time for impaired glucose and lipid metabolism to progress to more serious disease states, establishing IF as an early intervention, may be considered as a prudent form of preventative medicine.
- IF has shown to have other health benefits such as reduced blood pressure and may be considered as adjuvant therapy.
Considerations for future research:
- Compares the effects of IF on different ethnicities, sex and age categories
- Evaluates the effect of IF on other disease states e.g. cancer, auto-immune conditions
- Assesses the response of other biomarkers e.g. inflammatory cytokines
- Compares different types and durations of IF on health biomarkers (eg periodic, time restricted)
Abstract
The question of whether or not intermittent fasting diets improve the clinical indicators of glycolipid metabolism remains unclear. This study systematically reviewed the relevant clinical trials to evaluate the effects of intermittent fasting diet on glucose and lipid metabolism and insulin sensitivity in patients with metabolic syndrome. To evaluate the effect of intermittent fasting diet intervention on patients with disorders of glucose and lipid metabolism, random-effect or fixed-effect meta-analysis models were used to calculate the average difference before and after intermittent fasting diet intervention and the corresponding 95% confidence intervals (CIs). After intermittent fasting diet intervention, in terms of glucose metabolism, fasting blood glucose reduced by 0.15 mmol/L (95% CI: -0.23; -0.06), glycosylated hemoglobin reduced by 0.08 (95% CIs: -0.25; -0.10), insulin plasma levels reduced by 13.25 uUI (95% CIs: -16.69; -9.82), and HOMA-IR decreased by 0.31 on an average (95% CIs: -0.44; -0.19). In addition, BMI decreased by 0.8 kg/m2 (95% CIs: -1.32; -0.28), body weight reduced by 1.87 kg (95% CIs: -2.67; -1.07), and the waist circumference decreased by 2.08 cm (95% CIs: -3.06; -1.10). Analysis of lipid metabolism showed that intermittent fasting diet intervention effectively reduced the total cholesterol level by 0.32 mmol/L (95% CIs: -0.60; -0.05), low-density lipoprotein level by 0.22 mmol/L (95% CIs: -0.37; -0.07), and triglyceride level by 0.04 mmol/L (95% CIs: -0.15; -0.07). Intermittent fasting diets have certain therapeutic effects on blood glucose and lipids in patients with metabolic syndrome and significantly improve insulin resistance. It may be considered as an auxiliary treatment to prevent the occurrence and development of chronic diseases.
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10.
Effects of Oat Beta-Glucan Intake on Lipid Profiles in Hypercholesterolemic Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Yu, J, Xia, J, Yang, C, Pan, D, Xu, D, Sun, G, Xia, H
Nutrients. 2022;14(10)
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Dyslipidaemia is one of the risk factors associated with cardiovascular disease. Beta-glucan is a viscous soluble fibre found in microalgae, fungi and grains like oats, barley, sorghum etc. This systematic review and meta-analysis included thirteen randomised controlled trials to evaluate the effectiveness of oat beta-glucans on the lipid profiles of patients with hypercholesterolemia. This research showed a significant reduction in total cholesterol and low-density lipoprotein levels in hypercholesterolemic adults after beta-glucan intake. However, beta-glucans did not impact triglyceride and high-density lipoprotein cholesterol. Beta-glucan's effect on lipid profiles depended on the severity of hypercholesterolemia, the duration of the intervention, the source of beta-glucan, and the dosage of beta-glucan. Healthcare professionals can use the results of this study to understand the lipid profile-improving effects of beta-glucans in adults with moderate hypercholesterolemia. However, further robust studies are required to evaluate the effects of beta-glucan on lipid profiles and how the effect is affected by gender differences.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Consumption of oat beta glucans may be beneficial for improving total cholesterol and LDL-c in people with mild and moderate hypercholesterolemia
- The U.S Food and Drug Administration (FDA) recommends 3g or more of oat beta glucans per day to reap the benefits. This could be from 90g of oats (3 x 30g portions) or 1 30g portion of oats, 3 oatcakes and 1-2 tbsp of oat bran.
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:
Authors highlight that Hypercholesterolemia is a risk factor for cardiovascular disease and a symptom of Metabolic Syndrome. Hypercholesterolemia commonly includes; elevated levels of total cholesterol and low-density lipoprotein cholesterol (LDL-c) and lower levels of high-density lipoprotein cholesterol (HDL-c).
Conventional medical treatment for hypercholesterolemia is statins, however, statins can have a number of adverse side effects. For this reason, dietary interventions have been investigated including the use of oat beta-glucans for their potential lipid lowering effects.
The aim of this systematic review and meta-analysis was to synthesise and evaluate the evidence for the effects of oat beta-glucans on serum cholesterol and triglyceride (TG) levels in adults with hypercholesterolemia.
Thirteen randomised controlled trials (RCTs) published between 1999 – 2021 met the study inclusion criteria. These studies included a total population of 927 people aged between 38-76 years and from 7 different countries worldwide. The majority of participants were diagnosed with mild hypercholesterolemia.
Participants were randomised into an intervention group receiving dietary sources of oat beta-glucans or food with added oat beta-glucans or a placebo control group consisting of diets without beta-glucans.
Study lengths ranged from 3 to 8 weeks with doses of oat beta-glucans between 1.5g to 6g. The studies were also broken down into sub-groups for high and low doses of oat beta-glucan and mild and moderate hypercholesterolemia.
Baseline and endpoint cholesterol (total cholesterol C, HD-c & LDL-c) and triglycerides were used to assess the effectiveness of the interventions and a weighted mean difference (WMD) calculated with a 95% confidence interval (CI).
Key Findings:
- a reduction in total cholesterol (WMD = -0.24mmol/L; 95% CI)
- a reduction in LDL-c (WMD = -0.27mmol/L; 95% CI )
- Sub-groups found that oat beta-glucans reduced serum TG levels in patients with moderate hypercholesterolemia (WMD = -0.11 mmol/L; 95% CI) but not in cases of mild hypercholesterolemia. (WMD = -0.01 mmol/L; 95% CI)
- Higher daily doses of oat beta glucans had more positive effects on TG levels, however the results were not statistically significant in this meta-analysis
- <3g WMD -0.11 mmol/L; 95% CI: -0.13 to -0.08 mmol/L
- >3g WMD -0.00 mmol/L; 95% CI: -0.16 to -0.16 mmol/L
- Greater reductions in HDL -c were found in patients with moderate hypercholesterolemia (WMD-0.06 mmol/L; 95% CI; -0.07 to -0.05 mmol/L) compared to mild cases (WMD-0.01 mmol/L; 95% CI; -0.08 to -0.10 mmol/L).
Conclusion
Dietary intake of oat beta-glucans may support the reduction of total cholesterol and low density lipoprotein cholesterol, however, no significant changes were found for high density lipoprotein cholesterol or serum triglycerides. Due to the heterogeneity between studies and inconsistencies in results, more trials are needed with larger sample sizes and longer durations.
Notes: The authors reported no conflicts of interest.
Clinical practice applications:
Based on the pooled results of this meta-analysis:
- 1.5g -6g of dietary intake of oat beta-glucans could support a reduction of TC and LDL-c in cases of mild and moderate hypercholesterolemia
- Intake of oat beta glucans >3g may reduce TG levels
- HDl -c may be improved with oat beta glucan intake of between 1.5g to 6g for clients with moderate hypercholesterolemia.
Considerations for future research:
The findings of 8 of the 13 RCTs indicated that when compared to the control group, LDL-c could be lowered by oat beta-glucans whilst the other 5 trials did not. However, the cumulative results of this meta analysis found a reduction in LDL-c.
There were also several limitations to this study:
- Heterogeneity between studies and inconsistent results
- Short study duration
- Small populations and limited sample size
- The results varied for different levels of hypercholesterolemia
- Results may also differ by sex and source of oat beta glucans
Larger and longer trials are therefore needed to confirm the results.
Abstract
(1) Background: hyperlipidemia is one of the cardiovascular diseases which becomes a great threat to the health of people worldwide. Oat beta-glucan is reported to have a beneficial effect on lowering blood lipids. To probe the effect of oat beta-glucan consumption on serum lipid profiles (total cholesterol, total triglyceride, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol), we carried out a systematic search on randomized controlled trials of oat beta-glucan intervention on hypercholesterolemic individuals. (2) Methods: the pieces of literature were obtained from PubMed, Scopus, Cochrane Library, Web of Science, and the Embase from inception to 28 February 2022. The results were presented with the weighted mean difference (WMD) with a 95% CI. The random-effects or fixed-effects model was applied according to the heterogeneity. The subgroup analysis and meta-regression were used to identify the source of heterogeneity. (3) Results: thirteen trials with 927 participants were included in our meta-analysis. Overall, oat beta-glucan supplementation significantly reduced levels of TC (pooled WMD = -0.24 mmol/L; 95%CI: -0.28 to -0.20 mmol/L), LDL-c (pooled WMD = -0.27 mmol/L; 95%CI: -0.35 to -0.20 mmol/L). Furthermore, beta-glucan consumption did not show significant effects on TG (pooled WMD = -0.04 mmol/L; 95%CI: -0.13 to 0.05 mmol/L), HDL-c (pooled WMD = 0.00 mmol/L; 95%CI: -0.05 to 0.05 mmol/L). Subgroup analysis indicated that critical factors, such as disease severity of participants, the daily intervention of oat beta-glucan, source of oat beta-glucan, and duration of intervention had impacts on outcomes. (4) Conclusions: oat beta-glucan intake may significantly decrease the level of TC and LDL-c while no significant changes in TG and HDL-c were observed. This meta-analysis supports the health benefits of oat beta-glucan, especially for its cholesterol-lowering features, although it has some inevitable limitations.
keywords:"Cardiovascular Diseases" OR (Cardiovascular AND Diseases) OR "Cardiovascular Diseases" OR (cardiovascular AND disease) OR "cardiovascular disease"