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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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The Influence of Nutritional Intervention in the Treatment of Hashimoto's Thyroiditis-A Systematic Review.
Osowiecka, K, Myszkowska-Ryciak, J
Nutrients. 2023;15(4)
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Hashimoto’s thyroiditis is an autoimmune disorder characterized by the presence of antibodies in the thyroid gland such as thyroid peroxidase (TPO) and thyroglobulin (TG) antibodies. Immune-mediated inflammatory responses eventually lead to the progressive destruction of the gland and impaired thyroid function. The disease has a strong genetic disposition but is also influenced by environmental factors, including diet. Hence diet has been considered a complementary tool to manage thyroid function and disease progression by harnessing the benefits of certain nutrients and anti-inflammatory properties. This systematic review examined the effects of nutrients and dietary interventions on Hashimoto’s disease in current literature. Using antibody levels, thyroid hormone levels and body weight to measure outcomes. The review included 9 studies, all of which compared the intervention group to the control groups. The trials included looked at gluten-free, lactose-free and energy-restricted diets, with or without selected nutrients and foods supplements (ie. Nigella sativa, iodine). The intervention duration ranged from 3 weeks to 12 months. Despite the small number of trials, the data from those studies included in this review showed promising results. Improvements in disease parameters were observed in diets that were energy deficient, eliminated gluten, lactose and goitrogens or added Nigella sativa. Iodine restrictions did not show any improvements. In the discussion section, the authors presented the results in the wider context and the findings from other studies. Ultimately there appears to be a wide variance in outcomes, usually ranging from beneficial to neutral. The authors contributed to such variability due to the complexity of the condition and many influencing factors. Often participants in trials have highly variable thyroid status and function, and differences in regular dietary intakes of nutrients critical to thyroid health can easily distort the results. Hence much more specific research is needed to make firmer conclusions. Whereby no clear conclusions in larger groups could be drawn, potential benefits of dietary interventions in Hashimoto's disease may be much more apparent in clinical settings with personalized approaches that account for such individual variances.
Abstract
Diet can be a complementary treatment for Hashimoto's disease by affecting thyroid function and anti-inflammatory properties. It is still unclear which dietary strategy would be the most beneficial. The aim of this systematic review is to examine all the data currently available in the literature on the effects of nutritional intervention on biochemical parameters (anti-thyroid antibody and thyroid hormones levels) and characteristic symptoms in the course of Hashimoto's thyroiditis. This systematic review was prepared based on PRISMA guidelines. Articles in PubMed and Scopus databases published up to November 2022 were searched. As a result of the selection, out of 1350 publications, 9 were included for further analysis. The nutritional interventions included the following: elimination of gluten (3 articles) or lactose (1 article), energy restriction with or without excluding selected foods (n = 2), consumption of Nigella sativa (n = 2), or dietary iodine restriction (n = 1). The intervention duration ranged from 21 days to 12 months and included individuals with various thyroid function. Of the nine studies, three studies were female only. An improvement was observed during an energy deficit and after the elimination of selected ingredients (e.g., gluten, lactose, or goitrogens), as well as after the intervention of Nigella sativa. These interventions improved antibody levels against peroxidase (anti-TPO), (thyrotropin) TSH, and free thyroxine (fT4). No improvement was seen on the iodine-restricted diet. Varied outcomes of analyzed dietary interventions may be due to the heterogeneous thyroid condition, high variability between patients, and differences in habitual intake of critical nutrients (e.g., iodine, selenium, and iron) in different populations. Therefore, there is a great need for further experimental studies to determine whether any nutritional interventions are beneficial in Hashimoto's disease.
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The Effect of Regular Consumption of Reformulated Breads on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Schadow, AM, Revheim, I, Spielau, U, Dierkes, J, Schwingshackl, L, Frank, J, Hodgson, JM, Moreira-Rosário, A, Seal, CJ, Buyken, AE, et al
Advances in nutrition (Bethesda, Md.). 2023;14(1):30-43
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The metabolic effect of bread depends on several qualitative aspects ranging from the type of grain, the amount of carbohydrates, levels of other nutrients, as well as the chemical structure and processing. The aim of this study was to assess the certainty of the evidence and to investigate the overall effect of regular consumption of reformulated breads on glycaemic control in the following groups: a) healthy adults; b) those at risk of developing cardiometabolic disease (e.g., having hypertension, hyperglycaemia, hypercholesterolemia and/or overweight/obesity); and c) those with manifest type 2 diabetes mellitus (T2DM). This study is a systematic review and meta-analysis of 22 studies and 23 distinct study populations. All studies were randomised controlled trials, 12 of which had a crossover design and 10 had a parallel design. In total, 1037 participants were included. These provided 669 and 595 data points for intervention and control comparisons, respectively. Results show a beneficial effect of reformulated bread variants on fasting blood glucose concentrations. This benefit may be more pronounced among people with manifest T2DM (low certainty of evidence). Authors conclude that bread quality is relevant for metabolic health among adults and that future studies should address its relevance among people at risk of T2DM.
Expert Review
Conflicts of interest:
None
Take Home Message:
This study’s findings suggest the effect of reformulated breads high in dietary fibre, whole grains, and/or functional ingredients may be more beneficial than regular breads on fasting blood glucose concentrations in adults, primarily among those with T2DM. Reformulated breads however, did not lower fasting insulin concentrations, HOMA-IR and HbA1C when compared to regular bread.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Overview
This study evaluated the effect of regular consumption of “reformulated breads” on glycemic control among healthy adults, adults at cardiometabolic risk or with manifest T2DM in 22 RCTs with 1037 participants. Compared with “regular” or comparator bread, consumption of reformulated intervention breads yielded lower fasting blood glucose concentrations only among people with T2DM (low certainty of evidence), yet no differences in fasting insulin, HOMA-IR, HbA1c, or postprandial glucose response were identified.
[*’reformulated bread’ as defined by the World Health Organisation of altering the processing or composition of a food to improve its nutritional profile, and contained whole-grains and dietary fibre]
Results
Sub group analysis revealed that the effect of reformulated breads high in dietary fibre, whole grains, and/or functional ingredients on lowering fasting blood glucose was confined to participants with T2DM, with no significant effect among participants without T2DM (0.68 mmol/L; 95% CI: 1.11, 0.36; I2 1⁄4 57% and 0.04 mmol/L; 95% CI: 0.13, 0.05; I2 1⁄4 25%, respectively; P < 0.001).
Subgroup analyses by continent revealed a more pronounced effect on fasting blood glucose concentrations in studies conducted in Asia and the Middle East compared with studies conducted in Europe, North America, and Oceania (MD: 0.84 mmol/L; 95% CI: 1.35, 0.33; I2 1⁄4 52% and MD: 0.04 mmol/L; 95% CI: 0.10, 0.03; I2 1⁄4 0%, respectively; P < 0.001)
Additional subgroup analyses found that the type of control bread, but not the type of intervention bread, affected the pooled effect estimate of fasting blood glucose concentration (P 1⁄4 0.03), with the largest difference reported in studies not describing the control bread used.
Limitations
Publication bias was considered negligible for the studies included in this meta-analysis, and the risk of bias assessment revealed that most of the studies had some concerns of risk of bias. One author is a member of the International Carbohydrate Quality Consortium and another is a member of the GRADE working group.
Strengths
This systematic review and meta-analysis include the focus on high-quality intervention studies (i.e., RCTs using either crossover or parallel design) and the inclusion of longer-term studies (>2 wk) to address the effectiveness of regular bread replacement for glycemic control in everyday life.
Clinical practice applications:
- This data suggests that bread quality is relevant for metabolic health among adults at risk of T2DM. In particular, reformulated breads were found to have a more beneficial impact than regular breads on fasting blood glucose concentrations in adults with TsDM. However, consumption of the reformulated bread (enriched with dietary fiber, whole grains, or functional ingredients) did not lower fasting insulin concentrations compared with the control breads (MD: 1.59 pmol/L; 95% CI: 5.78, 2.59; moderate certainty of evidence)
- Consumption of the reformulated bread did not lower HOMA-IR compared with the control breads (MD: 0.09; 95% CI: 0.35, 0.22; moderate certainty of evidence)
- Consumption of the reformulated bread did not lower HbA1c concentrations compared with the control bread (0.14; 95% CI: 0.39, 0.10; P 1⁄4 0.195; very low certainty of evidence).
Considerations for future research:
- Longer intervention periods may be required to determine the beneficial effects on the HbA1c concentrations and to elicit changes in markers of insulin resistance
- Future studies should use the 2022 WHO standardised HbA1c diagnostic reference criterion for diabetes mellitus
- Improvements in specific outcomes may also be linked to defined groups within populations such as persons with manifest T2DM.
- The type of reformulation of the bread may be an important factor but differ considerably around the world
Abstract
Bread is a major source of grain-derived carbohydrates worldwide. High intakes of refined grains, low in dietary fiber and high in glycemic index, are linked with increased risk for type 2 diabetes mellitus (T2DM) and other chronic diseases. Hence, improvements in the composition of bread could influence population health. This systematic review evaluated the effect of regular consumption of reformulated breads on glycemic control among healthy adults, adults at cardiometabolic risk or with manifest T2DM. A literature search was performed using MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials. Eligible studies employed a bread intervention (≥2 wk) in adults (healthy, at cardiometabolic risk or manifest T2DM) and reported glycemic outcomes (fasting blood glucose, fasting insulin, HOMA-IR, HbA1c, and postprandial glucose responses). Data were pooled using generic inverse variance with random-effects model and presented as mean difference (MD) or standardized MD between treatments with 95% CIs. Twenty-two studies met the inclusion criteria (n = 1037 participants). Compared with "regular" or comparator bread, consumption of reformulated intervention breads yielded lower fasting blood glucose concentrations (MD: -0.21 mmol/L; 95% CI: -0.38, -0.03; I2 = 88%, moderate certainty of evidence), yet no differences in fasting insulin (MD: -1.59 pmol/L; 95% CI: -5.78, 2.59; I2 = 38%, moderate certainty of evidence), HOMA-IR (MD: -0.09; 95% CI: -0.35, 0.23; I2 = 60%, moderate certainty of evidence), HbA1c (MD: -0.14; 95% CI: -0.39, 0.10; I2 = 56%, very low certainty of evidence), or postprandial glucose response (SMD: -0.46; 95% CI: -1.28, 0.36; I2 = 74%, low certainty of evidence). Subgroup analyses revealed a beneficial effect for fasting blood glucose only among people with T2DM (low certainty of evidence). Our findings suggest a beneficial effect of reformulated breads high in dietary fiber, whole grains, and/or functional ingredients on fasting blood glucose concentrations in adults, primarily among those with T2DM. This trial was registered at PROSPERO as CRD42020205458.
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Brain-derived neurotrophic factor in diabetes mellitus: A systematic review and meta-analysis.
Moosaie, F, Mohammadi, S, Saghazadeh, A, Dehghani Firouzabadi, F, Rezaei, N
PloS one. 2023;18(2):e0268816
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Brain-derived neurotrophic factor (BDNF) is a key molecule mainly involved in brain cell growth. It is also responsible for the survival of beta cells of the pancreas, which produce a hormone known as insulin, which is responsible for balancing blood sugar. Poor functioning beta cells can result in the development of diabetes. It is unclear as to whether high or low BDNF is present in individuals with diabetes. This meta-analysis and systematic review of 2734 individuals aimed to determine BDNF levels in individuals with diabetes, depression, and diabetic retinopathy. The results showed that serum BDNF levels were low in individuals with diabetes, however plasma levels remained unchanged. BDNF was lower in individuals with type 2 diabetes, diabetes mellitus, depression, and diabetic retinopathy. It was concluded that decreased BDNF may contribute to the development of diabetes and associated complications. This study could be used by healthcare professionals to understand the close links between diabetes and brain disorders such as dementia and Alzheimer’s disease.
Abstract
BACKGROUND Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor expressed in several tissues, including the brain, gut, and pancreas. Activation of the BDNF/TrkB/CREB reduces hepatic gluconeogenesis, induces hepatic insulin signal transduction, and protects against pancreatic beta-cell loss in diabetes mellitus (DM). Several studies have investigated the possible association between BDNF and DM and its complications, but the results have been conflicting. AIM: In the present study, we aimed at systematically reviewing the literature on the serum and plasma levels of BDNF in DM and its subgroups such as T2DM, DM patients with depression, and patients with retinopathy. METHODS A comprehensive search was conducted in PubMed, Scopus, and Web of Science. We identified 28 eligible studies and calculated the standardized mean difference (SMD) of outcomes as an effect measure. RESULTS The meta-analysis included 2734 patients with DM and 6004 controls. Serum BDNF levels were significantly lower in patients with DM vs. controls (SMD = -1.00, P<0.001). Plasma BDNF levels were not different in patients with DM compared with controls. When conducting subgroup analysis, serum BDNF levels were lower among patients with T2DM (SMD = -1.26, P<0.001), DM and depression (SMD = -1.69, P<0.001), and patients with diabetic retinopathy (DR) vs. controls (SMD = -1.03, P = 0.01). CONCLUSIONS Serum BDNF levels were lower in patients with DM, T2DM, DM with depression, and DM and DR than the controls. Our findings are in line with the hypothesis that decreased BDNF levels might impair glucose metabolism and contribute to the pathogenesis of DM and its complications.
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A systematic review and meta-analysis of the correlation between polycystic ovary syndrome and irritable bowel syndrome.
Wei, Z, Chen, Z, Xiao, W, Wu, G
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2023;39(1):2239933
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The pathophysiology of polycystic ovarian syndrome (PCOS) and irritable bowel syndrome (IBS) remains elusive, the correlation between IBS and PCOS has been validated. This study's aim was to quantify the relationship between IBS and PCOS by estimating the odds ratio of IBS in PCOS patients. This study was a systematic review and meta-analysis of six studies in qualitative synthesis and five studies in quantitative synthesis. Results showed approximately 2.2 times elevated IBS risk in PCOS patient. Among six studies involved in this systematic review, a case-control study reported a negative relationship between IBS and PCOS, while most studies reported a positive association, which confirmed the pooled estimates results. Authors concluded that their study found a significant association between increased odds of IBS and PCOS.
Abstract
BACKGROUND Research on the prevalence of irritable bowel syndrome (IBS) among polycystic ovary syndrome (PCOS) patients has gained significant momentum over the years. However, it remains unclear whether PCOS is related to a higher prevalence of IBS. The objective of this systematic review and meta-analysis was to fully study IBS correlation with PCOS. METHODS From inception until October 16th, 2022, all observational studies documenting IBS prevalence in PCOS patients were collected from the China national knowledge infrastructure(CNKI), China Science and Technology Journal Database(VIP), Wanfang database, PubMed, Embase, Web of Science, and Cochrane databases. The quality of case-control studies was assessed with Newcastle-Ottawa Scale. Review Manager 5.3 was used to determine the pooled odds ratio (OR) and 95% confidence interval (CI). RESULTS 5 case-control studies involving 1268 individuals and one cross-sectional study involving 291 participants were included in our qualitative analysis. The quantitative analysis was conducted based on five case-control studies. Four case-control studies involving 1063 participants showed a higher prevalence of IBS in PCOS This meta-analysis revealed an almost twice higher risk of IBS in comparison with controls (OR = 2.23, 95%CI:1.58-3.14, p < 0.001; I2=41%, p = 0.150). Four sensitivity analyses validated the consistency of the aggregated findings. CONCLUSION This meta-analysis and systematic review demonstrated a significant association between PCOS and increased odds of IBS. However, more high-quality and well-controlled research is essential to increase the robustness of our conclusions.
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The Efficacy of Self-Management Strategies for Females with Endometriosis: a Systematic Review.
Mardon, AK, Leake, HB, Hayles, C, Henry, ML, Neumann, PB, Moseley, GL, Chalmers, KJ
Reproductive sciences (Thousand Oaks, Calif.). 2023;30(2):390-407
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Endometriosis is a gynaecological condition with symptoms of pelvic pain, fatigue, and stress. Decreased quality of life, impaired fertility and hinderances to carry out day to day tasks are all associated with endometriosis. Treatment options involve medications and surgery; however, both are associated with poorer outcomes than the initial disease itself. Self-management strategies that the individual can perform themselves, such as lifestyle changes, meditation, and rest have all been used to improve the quality of life of individuals with endometriosis, however their effectiveness has not been determined. This systematic review and meta-analysis aimed to determine the effectiveness of self-management strategies for the management of endometriosis. The study showed that many self-management strategies were no more effective than placebo or hormonal therapies for the management of endometriosis. It was concluded that many self-management strategies were no more effective than hormonal treatment at reducing endometriosis symptoms and the studies that did show a benefit were insufficient to base recommendations on due to poor design. This study could be used by healthcare professionals to understand that currently the research on self-management strategies of endometriosis is poor and whilst some may be of benefit to individuals who cannot or do not want to take hormone therapy, more research is warranted.
Expert Review
Conflicts of interest:
None
Take Home Message:
It is not possible to generalise the findings of this systematic review for the self-management of endometriosis due to the poor quality of evidence. Further studies of higher quality are needed.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Endometriosis is an inflammatory condition where endometrial-like tissue is found outside of the uterus. Diagnosis of endometriosis is made in around 6-10% of females of reproductive age. Endometriosis can adversely affect fertility, psychological well being and quality of life (QoL). Conventional interventions can have side effects and limited effectiveness. The aim of this systematic review (SR) was to evaluate the efficacy of self-management interventions for pain-related symptoms and QoL.
Methods
Fifteen experimental studies were included in this SR. Ten evaluated dietary supplements, three evaluated dietary modifications, one evaluated over-the-counter (OTC) medication, and one evaluated exercise. Outcome measures were self-reported for dysmenorrhoea, dyspareunia, overall pain, non-menstrual pelvic pain, use of medications and QoL.
Results
- Most dietary supplements were no more effective than placebo or frequently recommended medical interventions, at reducing pain-related outcomes.
- Melatonin (one RCT n=30) performed better than placebo for managing dysmenorrhoea and overall pain but not for non-menstrual pelvic pain. PEA-transploydatin (one RCT n=20) performed better than placebo for dysmenorrhoea and non-menstrual pelvic pain but not better than medical intervention.
- Resveratrol (one RCT n=22 & one intervention study n=12) plus the oral contraceptive pill (OCP) was more effective than the OCP alone for managing dysmenorrhoea.
- In one observational study, 75% of participants (n=295) reported a reduction in ‘high’ intensity pain scores following a 12-month gluten-free diet (p- value =<0.005). Similarly, a full dietary modification (one non randomised controlled trial , n=30) found less participants reporting pain at ‘high intensity’ (18%) compared to linseed and calcium oil supplements (41%) and placebo (62%).
- A metal trace element supplement was more effective than placebo for managing overall pain (one RCT p- value<0.001).
- Naproxen (one cross over trial, n=11) performed better than placebo at managing dysmenorrhoea (83% vs 41%, p- value 0.008).
- Hatha yoga (one RCT n=12) was found to be effective at reducing overall pain and improving QoL compared to no yoga (p-value <0.05).
Conclusion
Due to limited, low-quality evidence, high risk of bias and high levels of heterogeneity between studies, it was not possible to generalise the findings of the studies included in this systematic review. Further research of high-quality is needed in order to make self-management recommendations for females with endometriosis.
Notes: The authors reported no conflicts of interest.
Clinical practice applications:
Evidence-based self-management interventions are considered critical for the management of endometriosis. However, the quality of evidence in this SR was considered of poor quality. Further high-quality research is needed in order to be able to make recommendations. Strategies that showed potential benefits included:
- Dietary modifications and a gluten-free diet may be effective for reducing the intensity of pain associated with endometriosis.
- Hatha yoga may be effective at reducing overall pain and supporting psychological wellbeing and QoL.
Considerations for future research:
High quality studies are needed as well as a ‘gold standard’ definition for self-management criteria. Understanding potential barriers to self-management interventions may also be beneficial.
Abstract
Self-management is critical for the care of endometriosis. Females with endometriosis frequently use self-management strategies to manage associated symptoms; however, the efficacy of such strategies is unknown. The aim of this review was to systematically appraise the evidence concerning efficacy of self-management strategies for endometriosis symptoms. Electronic databases, including Medline, Embase, Emcare, Web of Science Core Collection, Scopus, and the Cochrane Central Register of Controlled Trials, were searched from inception to March 2021. We included peer-reviewed experimental studies published in English evaluating the efficacy of self-management strategies in human females laparoscopically diagnosed with endometriosis. Studies underwent screening, data extraction, and risk of bias appraisal (randomised studies: Risk of Bias 2 tool; non-randomised studies: Risk Of Bias In Non-randomized Studies - of Interventions tool). Of the fifteen studies included, 10 evaluated dietary supplements, three evaluated dietary modifications, one evaluated over-the-counter medication, and one evaluated exercise. Most studies had a high-critical risk of bias. Many self-management strategies were not more effective at reducing endometriosis symptoms compared to placebo or hormonal therapies. Where studies suggest efficacy for self-management strategies, no recommendations can be made due to the poor quality and heterogeneity of evidence. High-quality empirical evidence is required to investigate the efficacy of self-management strategies for females with endometriosis.
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Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis.
Zheng, SH, Chen, XX, Chen, Y, Wu, ZC, Chen, XQ, Li, XL
Reproductive biology and endocrinology : RB&E. 2023;21(1):79
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Endometriosis is a common gynaecological disorder in reproductive-age women which leads to infertility and pain symptoms. Current pain management approaches involve medications and surgical treatments, but their side effects and risk of recurrence have led to the exploration of alternative options. The aim of this study was to clarify the potential effects of antioxidant vitamins supplementation on endometriosis. This study was a systematic review and meta-analysis of eleven studies, comprising a total of 589 patients. Results showed that antioxidant vitamins supplementation can effectively alleviate endometriosis-related pain and reduce inflammatory markers. Authors conclude that antioxidant vitamins supplementation can be considered as an alternative treatment either on its own or in combination with other methods for managing endometriosis-related pain. However, further research would help to provide a clearer understanding of the role of antioxidant vitamins supplementation in women with endometriosis.
Abstract
OBJECTIVE This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. METHODS A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation. CONCLUSIONS The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain. TRIAL REGISTRATION PROSPERO registration number: CRD42023415198.
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Coffee Consumption and Risk of Hypertension in Adults: Systematic Review and Meta-Analysis.
Haghighatdoost, F, Hajihashemi, P, de Sousa Romeiro, AM, Mohammadifard, N, Sarrafzadegan, N, de Oliveira, C, Silveira, EA
Nutrients. 2023;15(13)
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High blood pressure (hypertension) is the main risk factor for cardiovascular diseases. Over the past decades the number of people experiencing high blood pressure has steadily increased, making it a serious concern for public health. Many dietary factors influence the development of high blood pressure, either increasing of decreasing the risk. Coffee is a widely consumed beverage. The caffeine in coffee can stimulate stress hormones like adrenaline. Adrenaline increases blood pressure, inflammation and decreases sensitivity to insulin, which are all regarded as risk factors for cardiovascular diseases. At the same time coffee contains many blood pressure lowering nutrients and compounds. Whether coffee contributes or diminishes the risks of developing high blood pressure has remained controversial. Hence, this systematic review and meta-analysis aimed to summarise the current evidence on coffee and hypertension risk. The analysis included 25 observational studies published between 2002 and 2023. The results concluded that coffee consumption was associated with a small reduction in risk for high blood pressure development. An inverse association was found, suggesting that as coffee consumption rose, high blood pressure risk falls. However, upon closer examination this inverse relationship was only found in the USA, but not in Europe and Asia. The authors suggested that geographics, genetics, gender, coffee preparation methods, and differences in lifestyle habits (smoking, salt consumption etc.) may contribute to the discrepancies between outcomes and make it harder to compare studies to form a uniform consensus. Hence, they urged for a cautious interpretation of the findings. In the absence of clear, consistent evidence, coffee consumption and cardiovascular risk may need to be assessed on an individual basis in clinical practice.
Abstract
OBJECTIVES The association between coffee intake and hypertension (HTN) risk is controversial. Therefore, this systematic review and meta-analysis aimed at summarizing the current evidence on the association of coffee with hypertension risk in observational studies. METHODS PubMed/Medline and Web of Science were searched for observational studies up to February 2023. Observational studies which assessed the risk of HTN in the highest category of coffee consumption in comparison with the lowest intake were included in the current meta-analysis (registration number: CRD42022371494). The pooled effect of coffee on HTN was evaluated using a random-effects model. RESULTS Twenty-five studies i.e., thirteen cross-sectional studies and twelve cohorts were identified to be eligible. Combining 13 extracted effect sizes from cohort studies showed that higher coffee consumption was associated with 7% reduction in the risk of HTN (95% CI: 0.88, 0.97; I2: 22.3%), whereas combining 16 effect sizes from cross-sectional studies illustrated a greater reduction in HTN risk (RR = 0.79, 95% CI: 0.72, 0.87; I2 = 63.2%). These results varied by studies characteristics, such as the region of study, participants' sex, study quality, and sample size. CONCLUSIONS An inverse association was found between coffee consumption and hypertension risk in both cross-sectional and cohort studies. However, this association was dependent on studies characteristics. Further studies considering such factors are required to confirm the results of this study.
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The effects of probiotics supplementation on glycaemic control among adults with type 2 diabetes mellitus: a systematic review and meta-analysis of randomised clinical trials.
Li, G, Feng, H, Mao, XL, Deng, YJ, Wang, XB, Zhang, Q, Guo, Y, Xiao, SM
Journal of translational medicine. 2023;21(1):442
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Type 2 diabetes mellitus (T2DM), an endocrine and metabolic disease, is influenced by host physiology and environmental factors. Recent studies have shown that the gut microbiota plays a key role in the maintenance of host homeostasis and pathogenesis of T2DM. The aim of this study was to evaluate the effects of a probiotic intervention on glycaemic control in T2DM patients and to evaluate the variations in these effects due to participant characteristics and intervention characteristics. This study was a systematic review and meta-analysis of thirty randomised-controlled studies including a total of 1,827 individuals. Results showed that probiotic supplementation had favourable effects on glycaemic control in T2DM patients. Bifdobacterium and food-type probiotics had greater glucose-lowering effects than other probiotic genera and types of vehicles used to deliver the probiotics. Authors concluded that the administration of probiotics may be a promising adjuvant therapy for glycaemic control in T2DM patients.
Abstract
OBJECTIVE This systematic review and meta-analysis study aimed to evaluate the effectiveness of probiotics supplementation on glycaemic control in patients with type 2 diabetes mellitus (T2DM) based on the data from the randomised clinical trials (RCTs). METHODS PubMed, Web of Sciences, Embase, and Cochrane Library were searched from the inception to October 2022, and RCTs about probiotics and T2DM were collected. The standardised mean difference (SMD) with 95% confidence interval (CI) was used to estimate the effects of probiotics supplementation on glycaemic control related parameters, e.g. fasting blood glucose (FBG), insulin, haemoglobin A1c (HbA1c), and homeostasis model of assessment of insulin resistance (HOMA-IR). RESULTS Thirty RCTs including 1,827 T2MD patients were identified. Compared with the placebo group, the probiotics supplementation group had a significant decrease in the parameters of glycaemic control, including FBG (SMD = - 0.331, 95% CI - 0.424 to - 0.238, Peffect < 0.001), insulin (SMD = - 0.185, 95% CI - 0.313 to - 0.056, Peffect = 0.005), HbA1c (SMD = - 0.421, 95% CI - 0.584 to - 0.258, Peffect < 0.001), and HOMA-IR (SMD = - 0.224, 95% CI - 0.342 to - 0.105, Peffect < 0.001). Further subgroup analyses showed that the effect was larger in the subgroups of Caucasians, high baseline body mass index (BMI ≥ 30.0 kg/m2), Bifidobacterium and food-type probiotics (Psubgroup < 0.050). CONCLUSION This study supported that probiotics supplementation had favourable effects on glycaemic control in T2DM patients. It may be a promising adjuvant therapy for patients with T2DM.
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Diabetes mellitus, prediabetes and the risk of Parkinson's disease: a systematic review and meta-analysis of 15 cohort studies with 29.9 million participants and 86,345 cases.
Aune, D, Schlesinger, S, Mahamat-Saleh, Y, Zheng, B, Udeh-Momoh, CT, Middleton, LT
European journal of epidemiology. 2023;38(6):591-604
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Diabetes mellitus and prediabetes may increase an individual’s risk for Parkinson’s disease (PD), however the research completed to date has been controversial. This meta-analysis of 15 observational studies with 86,345 individuals with PD aimed to update the research on PD risk for individuals with diabetes or prediabetes and determine possible reasons for the ambiguity of previous research. The results showed that compared to people without diabetes, those with, were at a 27% increased relative risk of PD and a 4% increase amongst those with prediabetes. Individuals with a history of complications alongside diabetes were at a higher risk than those without. It was concluded that the risk of developing PD is increased amongst individuals with diabetes. This study could be used by healthcare professionals to understand that individuals with diabetes may be at an increased risk for PD and should be monitored. However, as this is based on observational studies, there is a chance that PD increases the risk for diabetes and not the reverse.
Abstract
A diagnosis of diabetes mellitus and prediabetes has been associated with increased risk of Parkinson's disease (PD) in several studies, but results have not been entirely consistent. We conducted a systematic review and meta-analysis of cohort studies on diabetes mellitus, prediabetes and the risk of PD to provide an up-to-date assessment of the evidence. PubMed and Embase databases were searched for relevant studies up to 6th of February 2022. Cohort studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between diabetes, prediabetes and Parkinson's disease were included. Summary RRs (95% CIs) were calculated using a random effects model. Fifteen cohort studies (29.9 million participants, 86,345 cases) were included in the meta-analysis. The summary RR (95% CI) of PD for persons with diabetes compared to persons without diabetes was 1.27 (1.20-1.35, I2 = 82%). There was no indication of publication bias, based on Egger's test (p = 0.41), Begg's test (p = 0.99), and inspection of the funnel plot. The association was consistent across geographic regions, by sex, and across several other subgroup and sensitivity analyses. There was some suggestion of a stronger association for diabetes patients reporting diabetes complications than for diabetes patients without complications (RR = 1.54, 1.32-1.80 [n = 3] vs. 1.26, 1.16-1.38 [n = 3]), vs. those without diabetes (pheterogeneity=0.18). The summary RR for prediabetes was 1.04 (95% CI: 1.02-1.07, I2 = 0%, n = 2). Our results suggest that patients with diabetes have a 27% increased relative risk of developing PD compared to persons without diabetes, and persons with prediabetes have a 4% increase in RR compared to persons with normal blood glucose. Further studies are warranted to clarify the specific role age of onset or duration of diabetes, diabetic complications, glycaemic level and its long-term variability and management may play in relation to PD risk.