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The synergistic effect of herbal medicine and probiotics in pediatric functional constipation: A systematic review and meta-analysis.
Kim, E, Chang, S, Nam, J, Park, N, Min, SY
Medicine. 2024;103(7):e36899
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Paediatric functional constipation (PFC) is a prevalent gastrointestinal disorder in children. The initial approach to managing PFC involves demystification, education, toilet training, and the use of laxatives. Using laxatives can lead to various adverse effects therefore, patients with functional constipation typically adopt a self-management approach and explore complementary and alternative therapies. The aim of this study was to analyse the synergistic effect of herbal medicine (HM) combined with probiotics in the treatment of PFC, by comparing it to the use of probiotics alone. This study was a systematic review and meta-analysis of twenty-two randomised controlled trials. Results showed that the combination of HM with probiotics may yield significantly greater benefits for total effective rate when compared to probiotics alone. Furthermore, HM combined with probiotics could potentially reduce the recurrence rate by 70% compared to probiotics alone. Authors concluded that HM could potentially offer advantages in enhancing the efficacy rate and Bristol faecal score, influencing gastrointestinal peptide hormones, decreasing inflammation indicators and lowering the recurrence rate among children with functional constipation.
Abstract
BACKGROUND Pediatric functional constipation (PFC) is a prevalent and persistent gastrointestinal disorder, that requires various treatments, including alternative approaches. This review assessed the synergistic efficacy of herbal medicine (HM) and probiotics for PFC. METHODS We conducted a comprehensive search of 11 databases, including English, Chinese, and Korean databases, until June 29, 2023. The inclusion criteria were randomized clinical trials (RCTs) comparing the intervention of HM with probiotics to that of the same probiotics. Statistical analyses included calculation of the mean difference (MD), standardized MD, risk ratio (RR) with a 95% confidence interval (CI), and assessment of risk of bias using Review Manager Version 5.4 software. The Grading of Recommendations Assessment, Development, and Evaluation rating system was used to evaluate evidence quality. Potential publication bias was assessed using funnel plots, Egger test, the fail-safe N test, and Duval and Tweedie trim and fill method. RESULTS A total of 22 RCTs involving 2228 patients were included in the meta-analysis. The HM and probiotics group exhibited superior outcomes compared to the probiotics alone group in various parameters: total effective rate (RR: 1.24, 95% CI: 1.19-1.29, P < .001), Bristol fecal Score (MD: 0.80, 95% CI: 0.71-0.89, P < .001), gastrointestinal peptide hormone (motilin) (MD: 35.37, 95% CI: 24.64-64.10, P < .001), inflammation indicator (nitrous oxide) (MD: -12.45, 95% CI: -15.12 to -9.77, P < .001), minimal sensitive volume of the rectum (MD: -8.7, 95% CI: -10.91 to -6.49, P < .001), and recurrence rate (RR: 0.30, 95% CI: 0.21-0.43, P < .001). CONCLUSION The combination of HM and probiotics may exhibit a synergistic effect on PFC. Nevertheless, it is imperative to undertake rigorously planned RCTs to comprehensively evaluate the synergistic efficacy of HM and probiotics.
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Inverse Association Between Serum 25-Hydroxyvitamin D and Nonalcoholic Fatty Liver Disease.
Yuan, S, Larsson, SC
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2023;21(2):398-405.e4
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The prevalence of non-alcoholic fatty liver disease (NAFLD) is projected to increase due to the obesity epidemic, rise in diabetes prevalence, and other factors. An inverse association between serum 25-hydroxyvitamin D [S-25(OH)D], a clinical marker of vitamin D status, and NAFLD has been observed in several cross-sectional and case-control studies. The aim of this study was to determine the association between S-25(OH)D and NAFLD. This study is a 2-sample Mendelian randomisation study based on summary-level data of genome-wide association analyses on S-25(OH)D levels, NAFLD, and liver enzymes. Results show an inverse genetic correlation of S-25(OH)D with NAFLD and certain liver enzymes and an inverse association of genetically predicted S-25(OH)D with risk of NAFLD in European individuals. Authors conclude that vitamin D may play a role in NAFLD prevention. However, further studies are needed in order to confirm the causal effect of NAFLD on lowering S-25(OH)D levels.
Abstract
BACKGROUND & AIMS Serum 25-hydroxyvitamin D [S-25(OH)D] and nonalcoholic fatty liver disease (NAFLD) are correlated in many observational studies, whereas the causality of this association is uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to determine the association between S-25(OH)D and NAFLD. METHODS Seven and 6 independent genetic variants associated with S-25(OH)D and NAFLD at the genome-wide-significance level, respectively, were selected as instrumental variables. Summary-level data for S-25(OH)D were obtained from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium including 79,366 individuals. Summary-level data for NAFLD were available from a genome-wide association meta-analysis (1483 cases and 17,781 controls), the FinnGen consortium (894 cases and 217,898 controls), and the UK Biobank study (275 cases and 360,919 controls). Summary-level data for 4 liver enzymes were obtained from the UK Biobank. RESULTS There were genetic correlations of S-25(OH)D with NAFLD and certain liver enzymes. Genetically predicted higher levels of S-25(OH)D were consistently associated with a decreased risk of NAFLD in the 3 sources. For a 1-SD increase in genetically predicted S-25(OH)D levels, the combined odds ratio of NAFLD was 0.78 (95% confidence interval [CI], 0.69 to 0.89). Genetically predicted higher levels of S-25(OH)D showed a borderline association with aspartate aminotransferase levels (change -1.17; 95% CI, -1.36 to 0.01). Genetic predisposition to NAFLD was not associated with S-25(OH)D (change 0.13; 95% CI, -1.26 to 0.53). CONCLUSIONS Our findings have clinical implications as they suggest that increased vitamin D levels may play a role in NAFLD prevention in European populations.
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Plum supplementation and lipid profile: a systematic review and meta-analysis of randomised controlled trials.
Askarpour, M, Ghalandari, H, Setayesh, L, Ghaedi, E
Journal of nutritional science. 2023;12:e6
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The rate of nutrition-related non-communicable diseases is increasing worldwide. Lipid profile and its alterations have been used both as indicators of metabolic disorders and methods to evaluate patients’ response to dietary interventions. The aim of this study was to investigate the effectiveness of plums on improving parameters of lipid profile. This study is a systematic review and meta-analysis of nine randomised controlled trials with a total of eleven arms and 592 participants. Results show that plum can be beneficial in reducing triacylglycerols [triglycerides] in the unhealthy and low-density lipoprotein cholesterol in all individuals. However, no significant impact regarding blood triacylglycerols and high-density lipoprotein cholesterol levels, could be detected both in crude and subgroup analyses. Authors conclude that further clinical trials, taking advantage of a standard protocol of plum supplementation, should be conducted to elucidate the possible effect that plum supplementation might exert on lipid profile parameters.
Abstract
Plums are abundant in bioactive compounds which have been associated with numerous health benefits. In the present study, we aimed at examining the impact of plum supplementation on lipid profile of individuals. Electronic bibliographical databases were searched for relevant randomised clinical trials. Articles meeting our eligibility criteria were included for data extraction and final analysis. Weighted mean difference (WMD) was estimated using a random-effect model. Of the total articles retrieved in the initial search, nine articles were found to be eligible to be included in the analysis. Our results show that plum supplementation significantly improves total cholesterols levels in the unhealthy individuals. Moreover, plum supplementation reduces the LDL-c levels in the pooled sample (WMD = -11⋅52 mg/dl; 95 % CI -21⋅93, -1⋅11, P = 0⋅03, I 2 = 98⋅7 %) and also in some of the subgroups of individuals (dried plum, unhealthy subjects, duration more than 8 weeks). Moreover, it had a significant reducing effect on TC levels just in unhealthy subjects. Although plum supplementation did not have any significant impact on serum levels of TG nor HDL-c. Our results show that supplementation with plums is potentially effective in reducing serum total cholesterol and LDL-c.
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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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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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Effect of omega-3 supplementation on lipid profile in children and adolescents: a systematic review and meta-analysis of randomized clinical trials.
Khorshidi, M, Hazaveh, ZS, Alimohammadi-Kamalabadi, M, Jamshidi, S, Moghaddam, OM, Olang, B, Hatefi, S, Hosseini, A, Jamilian, P, Zarezadeh, M, et al
Nutrition journal. 2023;22(1):9
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Dyslipidaemia is considered as a substantial risk factor for cardiovascular disease (CVD). It is characterised by increased levels of triglyceride and low-density lipoprotein (LDL) and decreased levels of high-density lipoprotein (HDL). Consumption of omega-3 supplements play an important role in reduction of CVD events and its associated mortality by ameliorating lipid profile via lowering triglyceride levels. The aim of this study was to evaluate the effect of omega 3 supplementation on lipid profile in children and adolescents. This study is a systematic review and meta-analysis of fourteen studies. Three trials out of 14 had cross-over design, while others were parallel randomised trials. Results show that omega-3 supplementation may exert therapeutic effects on triglyceride (TG) levels, however, there weren’t any remarkable effects on HDL, LDL, and total cholesterol status. The subgroup analysis showed an improvement in TG levels in studies conducted on participants ≤13 years old and those with hypertriglyceridemia. Furthermore, due to meta-regression results, the omega-3 supplementation improved HDL levels when administered with longer duration. Authors conclude that omega-3 supplementation may have favourable hypolipidemic effects through reduction of TG levels. Additionally, clinical trials with longer duration of intervention and appropriate designs are recommended for younger children and those with hypertriglyceridemia.
Abstract
PURPOSE Dyslipidemia is considered as a known risk factor for cardiovascular disease. Yet various trials with wide ranges of doses and durations have reported contradictory results. We undertook this meta-analysis of randomized controlled trials (RCTs) to determine whether omega-3 supplementation can affect lipid profile in children and adolescents. METHODS Cochrane Library, Embase, PubMed, and Scopus databases were searched up to March 2021. Meta-analysis was performed using random-effect method. Effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was assessed using the I2 index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta-regression analysis was conducted. RESULTS A total of 14 RCTs with 15 data sets were included. Based on the combination of effect sizes, there was a significant reduction in TG levels (WMD: -15.71 mg/dl, 95% CI: -25.76 to -5.65, P=0.002), with remarkable heterogeneity (I2=88.3%, P<0.001). However, subgroup analysis revealed that omega-3 supplementation significantly decreased TG only in studies conducted on participants ≤13 years old (WMD=-25.09, 95% CI: -43.29 to -6.90, P=0.007), (I2=84.6%, P<0.001) and those with hypertriglyceridemia (WMD=-28.26, 95% CI: -39.12 to -17.41, P<0.001), (I2=0.0%, P=0.934). Omega-3 supplementation had no significant effect on total cholesterol, HDL, and LDL levels. Also, results of nonlinear analysis showed significant effect of treatment duration on HDL status (Pnon-linearity=0.047). CONCLUSION Omega-3 supplementation may significantly reduce TG levels in younger children and those with hypertriglyceridemia. Also, based on the HDL-related results, clinical trials with longer duration of intervention are recommended in this population.
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High-protein diets and testosterone.
Whittaker, J
Nutrition and health. 2023;29(2):185-191
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High protein diets have been shown to have several benefits such as weight loss and the promotion of feeling fuller for longer following food. A recent study has however shown that testosterone levels are decreased in men who follow a high protein diet. This study aimed to summarise the data on high protein diets and testosterone. The results showed that diets with more than 3.4g/kg/day protein decreased total testosterone levels possibly due to the body adjusting its biochemistry to ensure that the excess protein in the diet is metabolised. Furthermore, inflammation in response to an increased amount of protein may suppress testosterone production. It was concluded that increased protein intake of more than 3.4g/kg/day drives the decrease in total testosterone in the body of men regardless of what happens to the level of carbohydrate and fat in the body. This study could be used by healthcare professionals to understand that high protein diets may decrease testosterone levels in men.
Abstract
A recent meta-analysis found low-carbohydrate, high-protein diets (> 3.4 g/kg of bodyweight/day) (g/kg/day) decreased men's total testosterone (∼5.23 nmol/L) [Whittaker and Harris (2022) Low-carbohydrate diets and men's cortisol and testosterone: systematic review and meta-analysis. Nutrition and Health. DOI: 10.1177/02601060221083079]. This finding has generated substantial discussion, however, it has often lacked clarity and context, with the term 'high-protein' being used unqualified. Firstly, diets < 3.4 g/kg/day are not associated with a consistent decrease in testosterone. Secondly, the average protein intake is ∼1.3 g/kg/day, conventional 'high-protein' diets are ∼1.8-3 g/kg/day and the vast majority of athletes are < 3.4 g/kg/day; meaning very few individuals will ever surpass 3.4 g/kg/day. To avoid such confusion in the future, the following definitions are proposed: very high (> 3.4 g/kg/day), high (1.9-3.4 g/kg/day), moderate (1.25-1.9 g/kg/day) and low (<1.25 g/kg/day). Using these, very high-protein diets (> 3.4 g/kg/day) appear to decrease testosterone, however high- and moderate-protein diets (1.25-3.4 g/kg/day) do not.
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Vegetarian and vegan diets and the risk of cardiovascular disease, ischemic heart disease and stroke: a systematic review and meta-analysis of prospective cohort studies.
Dybvik, JS, Svendsen, M, Aune, D
European journal of nutrition. 2023;62(1):51-69
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Cardiovascular disease (CVD) is mainly due to ischemic heart disease (IHD) and stroke. Plant-based diets are effective for improving CVD risk factors. This is further supported by the favourable cardiometabolic profile seen among vegetarians who predominantly exclude meat, fish and poultry from their diet, when compared to people consuming meat. The aim of this study was to analyse the association between vegetarian or vegan diets and risk of incidence and mortality from CVD, IHD and stroke, both overall and subtypes. This study is a systematic review and meta-analysis of thirteen prospective cohort studies. Results show a 15% and a 21% reduction in the relative risk of CVD and IHD, respectively, for vegetarians compared to nonvegetarians, but there wasn’t a clear association for total stroke or subtypes of stroke. Furthermore, an 18% reduction in the relative risk of IHD was observed among vegans when compared to nonvegetarians but the association lacked precision and no clear association was observed for CVD or stroke; however, there were few studies in the analyses of vegans. Authors conclude that their findings are consistent with existing guidelines recommending plant-based dietary patterns for CVD prevention. However, further studies are required to clarify the association between vegetarian diets and stroke risk, as well as the association between vegan diets and IHD.
Abstract
PURPOSE Vegetarian diets have been associated with reduced risk of ischemic heart disease (IHD). However, results regarding cardiovascular disease (CVD) overall and stroke are less clear. We conducted a systematic review and meta-analysis of prospective cohort studies on CVD, IHD and stroke risk among vegetarians or vegans versus nonvegetarians to clarify these associations. METHODS PubMed and Ovid Embase databases were searched through August 12, 2021. Prospective cohort studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for incidence or mortality from CVD, IHD and stroke, comparing vegetarians and vegans to nonvegetarians were included. Risk of bias (RoB) was assessed using ROBINS-I and the strength of evidence was assessed using World Cancer Research Fund (WCRF) criteria. Summary RRs (95% CIs) were estimated using a random effects model. RESULTS Thirteen cohort studies (844,175 participants, 115,392 CVD, 30,377 IHD, and 14,419 stroke cases) were included. The summary RR for vegetarians vs. nonvegetarians was 0.85 (95% CI: 0.79-0.92, I2 = 68%, n = 8) for CVD, 0.79 (95% CI: 0.71-0.88, I2 = 67%, n = 8) for IHD, 0.90 (95% CI: 0.77-1.05, I2 = 61%, n = 12) for total stroke, and for vegans vs. nonvegetarians was 0.82 (95% CI: 0.68-1.00, I2 = 0%, n = 6) for IHD. RoB was moderate (n = 8) to serious (n = 5). The associations between vegetarian diets and CVD and IHD were considered probably causal using WCRF criteria. CONCLUSIONS Vegetarian diets are associated with reduced risk of CVD and IHD, but not stroke, but further studies are needed on stroke. These findings should be considered in dietary guidelines. REVIEW REGISTRATION No review protocol registered.
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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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Do Colonic Mucosal Tumor Necrosis Factor Alpha Levels Play a Role in Diverticular Disease? A Systematic Review and Meta-Analysis.
Sabo, CM, Ismaiel, M, Ismaiel, A, Leucuta, DC, Popa, SL, Grad, S, Dumitrascu, DL
International journal of molecular sciences. 2023;24(12)
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Diverticular disease (DD) is a disease of the colon that can be split into symptomatic uncomplicated diverticular disease (SUDD), asymptomatic complicated, and segmental colitis associated with diverticulosis (SCAD). They are all diseases of the colon that are poorly understood. It is thought that inflammation of the colon may play a part in their development, however levels of certain inflammatory biomarkers have shown contradicting relationships. This systematic review of 12 studies and meta-analysis of 6 of these aimed to determine the role of one inflammatory biomarker known as tumour necrosis factor-alpha (TNF-a) in DD. The results showed that mucosal TNF-a levels were unchanged in individuals with SUDD compared to healthy controls. They were also unchanged in SUDD vs asymptomatic DD. They were higher in individuals with DD and SCAD when compared to individuals with irritable bowel syndrome (IBS). It was concluded that TNF-a may be involved in the development of specific types of DD. This study could be used by healthcare professionals to understand that the management of inflammation in individuals with DD may be of benefit.
Abstract
Diverticular disease (DD) is the most frequent condition in the Western world that affects the colon. Although chronic mild inflammatory processes have recently been proposed as a central factor in DD, limited information is currently available regarding the role of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). Therefore, we conducted a systematic review and meta-analysis aiming to assess the mucosal TNF-α levels in DD. We conducted a systematic literature search using PubMed, Embase, and Scopus to identify observational studies assessing the TNF-α levels in DD. Full-text articles that satisfied our inclusion and exclusion criteria were included, and a quality assessment was performed using the Newcastle-Ottawa Scale (NOS). The principal summary outcome was the mean difference (MD). The results were reported as MD (95% confidence interval (CI)). A total of 12 articles involving 883 subjects were included in the qualitative synthesis, out of which 6 studies were included in our quantitative synthesis. We did not observe statistical significance related to the mucosal TNF-α levels in symptomatic uncomplicated diverticular disease (SUDD) vs. the controls (0.517 (95% CI -1.148-2.182)), and symptomatic vs. asymptomatic DD patients (0.657 (95% CI -0.883-2.196)). However, the TNF-α levels were found to be significantly increased in DD compared to irritable bowel disease (IBS) patients (27.368 (95% CI 23.744-30.992)), and segmental colitis associated with diverticulosis (SCAD) vs. IBS patients (25.303 (95% CI 19.823-30.784)). Between SUDD and the controls, as well as symptomatic and asymptomatic DD, there were no significant differences in the mucosal TNF-α levels. However, the TNF-α levels were considerably higher in DD and SCAD patients than IBS patients. Our findings suggest that TNF-α may play a key role in the pathogenesis of DD in specific subgroups and could potentially be a target for future therapies.
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Effect of L-Carnosine in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis.
Sureshkumar, K, Durairaj, M, Srinivasan, K, Goh, KW, Undela, K, Mahalingam, VT, Ardianto, C, Ming, LC, Ganesan, RM
Frontiers in bioscience (Landmark edition). 2023;28(1):18
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L-carnosine is naturally produced in the body and is found in high concentrations in the brain, muscles and gut. It has many roles including acting as an anti-inflammatory and antioxidant. As such, it may have a role in the prevention and management of many different chronic diseases such as cancer, heart disease, diabetes and brain degenerative disorders. This systematic review and meta-analysis aimed to determine the clinical usage of L-carnosine in these chronic diseases. The study included 14 different studies and showed that L-carnosine supplementation may be a potential therapy for age related diseases such as diabetes and brain degenerative diseases. No studies were found for its use in individuals with cancer and the current evidence does not support its use in heart disease. It was concluded that L-carnosine is of benefit to individuals with diabetes and cognitive impairment, but not heart disease. This study could be used by health care professionals to understand that L-carnosine supplementation may be of benefit to indivduals with diabetes and neurodegenerative disorders.
Abstract
INTRODUCTION L-carnosine has been found to have multimodal activity. AIM: The aim of this review was to find out the efficacy of L-carnosine in patients with age-related diseases. METHODS Clinical studies evaluated the effect of L-carnosine on cancer, cardiovascular disease, diabetes, and neurodegenerative disorders were searched in electronic bibliographic databases. The protocol has been registered with PROSPERO (CRD42022314033). The revised Cochrane risk of bias tool for randomized trials was used to assess all of the reports for risk of bias. RevMan 5.4 was used to conduct the meta-analysis. RESULTS Following the screening process, 14 papers were selected for systematic review, with 9 of them being qualified for meta-analysis. Many of the included studies showed that L-carnosine has potential therapeutic activity in age related diseases. Results from the meta-analysis showed that in diabetes mellitus, HbA1c [mean difference (MD) 95% CI = -1.25 (-2.49, -0.022); p = 0.05; p = 0.001; I2 = 85%] and fasting blood sugar (FBS) [MD 95% CI = -12.44 (-22.44, -2.44); p = 0.01; p = 0.40; I2 = 0%] and in neurodegenerative disorder, Wechsler Memory Scale Logical Memory 2 (WMS-LM2) [MD 95% CI = 1.34 (0.83, 1.85); p < 0.00001; p = 0.43; I2 = 0%], showed statistically significant difference, favoring the L-carnosine group over the control group. While in neurodegenerative disorder, Alzheimer 's Disease Assessment Scale (ADAS) [MD 95% CI = 0.98 (-1.55, -0.42); p = 0.0007; p = 0.86; I2 = 0%] and Back Depression Inventory (BDI) [MD 95% CI = -1.12 (-1.87, -0.37); p = 0.003; p = 0.73; I2 = 0%] showed statistically significant difference, favoring the control group over L-carnosine group. CONCLUSIONS Clinical studies were conducted to manage chemotherapy induced toxicities and there are no clinical studies available for its anti-cancer use, and the current evidence does not support its use in the treatment of cardiovascular disease.