1.
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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Plain language summary
Type 2 diabetes mellitus (T2DM), characterised by sustained hyperglycaemia and insulin resistance, remains a severe driver of chronic metabolic diseases such as cardiovascular diseases. The aim of this study was to investigate and compare the efficacy of vitamin and mineral supplements in the management of glycaemic control and lipid metabolism for type 2 diabetic patients to inform clinical practice. This study is a systematic review and meta-analysis of one hundred and seventy articles with a total of 4223 adults with T2DM. Participants were randomised to either the placebo/no treatment group (n= 6345) or to the treatment group (n= 7878). Results show that: - chromium was the most effective micronutrient for decreasing fasting blood glucose and insulin resistance. - vitamin K was the top-ranked micronutrient in reducing haemoglobin A1C and fasting insulin levels. - vanadium was the top-ranked micronutrient in total cholesterol reductions. - niacin was ranked as the most effective in triglycerides reductions and increasing high-density lipoprotein cholesterol levels. - vitamin E was the top-ranked micronutrient in low-density lipoprotein cholesterol reductions. Authors conclude that micronutrient supplements especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more effective in the management of T2DM compared with other micronutrients.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Clinicians could consider the adjunctive effect of micronutrients supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements in a nutrition protocol to manage T2DM and slow or prevent its complications.
- The study authors state that the vitamin and mineral supplements under review had a statistically significant improvement, however they did not reach the study threshold for clinical significance. Therefore they advise caution in utilising micronutrient supplements in the management of glucose and lipid metabolism for T2DM.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Objectives
The aim of this systematic review was to evaluate the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM).
Methodology
This systematic review is registered with PROSPERO and adhered to PRISMA-2020 guidelines for network meta-analysis
The Cochrane Collaboration’s risk-of-bias tool was used to assess eligible randomised trials
8 prespecified markers identified and assessed in this study : 1) HbA1c (%), 2) fasting blood glucose (mmol/L), 3) total cholesterol (mmol/L), 4) triglycerides (mmol/L), 5) fasting insulin (μIU/mL), 6) HOMA-IR, 7) LDL-c (mmol/L), and 8) HDL-c (mmol/L).
Results
- 170 RCT trials of 14223 participants with T2DM treated with vitamin supplements, mineral supplements, or placebo/no treatment were included
- Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively)
- Vitamin K supplements ranked best in reducing glycated haemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence
- Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%)
- Niacin supplements ranked best in triglyceride reductions and increasing high-density lipo-protein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively)
- Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%).
Conclusion
- Micronutrient supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be efficacious in managing T2DM
- It should be noted that the evidence certainty for all was low.
Clinical practice applications:
- Chromium plays an important role in carbohydrate and lipid metabolism and was the most effective micronutrient for decreasing fasting blood glucose, HbA1c, fasting insulin, and HOMA-IR reductions. More pronounced effects were seen for chromium than vitamin E, vitamin C, niacin, selenium, and magnesium supplements
- Vitamin K was the top-ranked micronutrient in reducing HbA1c and fasting insulin levels. The mechanism through which Vitamin K affects glucose metabolism is proposed as activation of the AMP-activated protein kinase/sirtuin 1, that in turn increases phosphocreatine 3-kinase and glucose transporter 2 to decrease insulin resistance and fasting glucose.
- Vanadium was the top-ranked micronutrient in total cholesterol (TC) reductions, where supplementation dosage should be carefully considered, as vanadium compounds can be moderately or highly toxic. Vanadium supplementation is only recommended in cases of vanadium deficiency or diabetes, hyperlipidemia, and hypertension, where the intake of vanadium from food should be enhanced in preference to supplementation
- Niacin was ranked as the most effective in triglyceride (TG) reductions and increasing HDL cholesterol levels. The dose of niacin could not be determined
- Vitamin E was the top-ranked micronutrient in low-density lipo- protein (LDL) cholesterol reductions.
Considerations for future research:
- Considering the clinical importance of these findings, new research is needed to get better insight into the efficacy of micronutrient supplements in managing T2DM
- Selenium homeostasis, selenoprotein, insulin signaling/secretion, and carbohydrate/lipid metabolism are linked in multiple and complex ways but the authors could not explain why chromium supplementation would lower blood glucose more effectively than selenium supplementation, and suggest more research is needed to clarify this
- While vitamin K status could be an emerging treatment target in T2DM prevention and management, it remains to be determined whether vitamin K supplementation has an advantage over other nutrients in terms of hypoglycemic effect, and further research is necessary
- The beneficial effect of vitamin E and niacin supplements regarding lipid metabolism warrant investigation through more rigorous comparative studies.
Abstract
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
2.
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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Plain language summary
The metabolic effect of bread depends on several qualitative aspects ranging from the type of grain, the amount of carbohydrates, levels of other nutrients, as well as the chemical structure and processing. The aim of this study was to assess the certainty of the evidence and to investigate the overall effect of regular consumption of reformulated breads on glycaemic control in the following groups: a) healthy adults; b) those at risk of developing cardiometabolic disease (e.g., having hypertension, hyperglycaemia, hypercholesterolemia and/or overweight/obesity); and c) those with manifest type 2 diabetes mellitus (T2DM). This study is a systematic review and meta-analysis of 22 studies and 23 distinct study populations. All studies were randomised controlled trials, 12 of which had a crossover design and 10 had a parallel design. In total, 1037 participants were included. These provided 669 and 595 data points for intervention and control comparisons, respectively. Results show a beneficial effect of reformulated bread variants on fasting blood glucose concentrations. This benefit may be more pronounced among people with manifest T2DM (low certainty of evidence). Authors conclude that bread quality is relevant for metabolic health among adults and that future studies should address its relevance among people at risk of T2DM.
Expert Review
Conflicts of interest:
None
Take Home Message:
This study’s findings suggest the effect of reformulated breads high in dietary fibre, whole grains, and/or functional ingredients may be more beneficial than regular breads on fasting blood glucose concentrations in adults, primarily among those with T2DM. Reformulated breads however, did not lower fasting insulin concentrations, HOMA-IR and HbA1C when compared to regular bread.
Evidence Category:
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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.