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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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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.
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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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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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3.
Effects of exercise training programmes on fasting gastrointestinal appetite hormones in adults with overweight and obesity: A systematic review and meta-analysis.
Almesbehi, T, Harris, L, McGarty, A, Alqallaf, S, Westrop, S, Edwards, CA, Dorling, JL, Malkova, D
Appetite. 2023;182:106424
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Appetite is controlled by several hormones including those of the gastrointestinal (GI) system. There has been controversy over whether exercise can affect these hormones resulting in altered food intake and this systematic review and meta-analysis aimed to address this. The results showed that 9 studies have been performed aimed at the effect of 16 different exercise interventions on appetite hormones of the GI system. Exercise had no effect on total ghrelin, acetylated ghrelin and peptide YY, however body mass index and body mass were significantly reduced in individuals with obesity or who are overweight. It was concluded that any increased appetite or energy intake during exercise interventions is unlikely related to GI appetite hormones. This study could be used by healthcare professionals to understand that although exercise may not affect food intake it can still aid weight loss in individuals who are overweight or obese.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This systematic review and meta-analysis found that exercise training programmes in individuals living with overweight and obesity have no impact on fasting concentrations of total and acylated ghrelin, PYY, GLP-1 and CCK.
- This finding suggests that any increase in appetite and energy intake typical of exercise training, would be related to different factors and not from changes in fasting concentrations of gastrointestinal appetite hormones.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
Overweight and obesity prevalence is increasing globally. Exercise is advocated as an effective preventive and treatment for obesity. However, exercise may affect appetite regulation, and understanding how this functions in people with overweight and obesity is of interest. Notably, the evidence regarding the effects of exercise training on gastrointestinal hormones such as ghrelin, has not been extensively synthesised.
Aim
- The aim of this systematic review and meta-analysis was therefore to synthesise the literature describing the effect of exercise programmes of >4 weeks’ duration from randomised controlled trials (RCT) on the fasting and gastrointestinal appetite hormones of adults living with overweight and obesity.
- The review followed PRISMA reporting guidelines and standard systematic review and meta analysis methodology.
Results
- After screening 13,204 records, nine studies with a total of 707 participants (259 men and 448 women) were identified that fit the pre-defined inclusion criteria and were included in the review.
- Overall, after exercise interventions in comparison to control, there was a reduction in body mass (effect size (d)= −0.22, 95% CI −0.42 to −0.03, p = 0.03; 7 studies) and BMI (d= −0.31, 95% CI −0.50 to −0.12, p = 0.001; 8 studies).
- Exercise had no impact on total fasting ghrelin (d = 1.06; 95% CI -0.38 to 2.5; p=0.15; 4 interventions) or fasting acylated ghrelin concentration (d = 0.08; 95% CI -0.31 to 0.47; p=0.68; 7 interventions).
- Fasting anorexigenic peptide YY did not differ between exercise and control (d = −0.16, 95% CI: −0.62 to 0.31, P = 0.51; 7 interventions).
- Two studies assessed the effects of exercise training on GLP-1 and meta-analyses were not possible. In one study, fasting GLP-1 was higher in the intervention group (p=0.04) though the other study found no difference (P>0.05). Only one study looked at fasting plasma cholecystokinin (CCK), which found no change between exercise and control interventions (p>0.5).
- When looking at the correlation between body mass and appetite hormone changes, weight loss (p<0.05) and BMI reduction (p<0.05) occurring with exercise was positively associated with an increase in total plasma ghrelin (p<0.05); increased ghrelin was associated to reductions in body weight and BMI (both p<0.0001). Further, one study reported a positive correlation of body mass loss and BMI reduction with a reduction in acylated ghrelin (p=0.003 and 0.009, respectively) and negatively with an increase in plasma PYY concentration (p=0.003 and 0.03, respectively).
Clinical practice applications:
This systematic review suggested that any compensatory increase in energy intake due to exercise training is unlikely to be related to fasting gastrointestinal appetite hormone changes. Therefore, nutritional therapists should bear this in mind when consulting with clients and find personalised lifestyle strategies to help people manage their caloric consumption in relation to exercise training.
Considerations for future research:
- The relation between changes in body mass or BMI and fasting appetite hormones could not be fully explored due to the small number of studies included in this review. Moreover, the results of this review should be interpreted with caution because most studies were underpowered with a high risk of bias, and there was considerable heterogeneity within some meta-analyses. The effect of exercise training on gastrointestinal satiety hormones including ghrelin, PYY, and CCK therefore require further investigation in individuals living with overweight and obesity, in order to reach more substantial conclusions.
- Exercise enhances the coupling between energy intake and energy expenditure after food consumption, where controlled studies are needed to test how postprandial concentrations of gastrointestinal hormones are influenced by exercise training in individuals with overweight and obesity.
Abstract
A systematic review and meta-analysis was performed to determine the effect of exercise training on fasting gastrointestinal appetite hormones in adults living with overweight and obesity. For eligibility, only randomised controlled trials (duration ≥ four weeks) examining the effect of exercise training interventions were considered. This review was registered in the International Prospective Register of Systematic Reviews (CRD42020218976). The searches were performed on five databases: MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus. The initial search identified 13204 records. Nine studies, which include sixteen exercise interventions, met the criteria for inclusion. Meta-analysis was calculated as the standardised mean difference (Cohen's d). Exercise training had no effect on fasting concentrations of total ghrelin (d: 1.06, 95% CI -0.38 to 2.50, P = 0.15), acylated ghrelin (d: 0.08, 95% CI: -0.31 to 0.47, P = 0.68) and peptide YY (PYY) (d = -0.16, 95% CI: -0.62 to 0.31, P = 0.51) compared to the control group. Analysis of body mass index (BMI) (d: -0.31, 95% CI: -0.50 to -0.12, P < 0.01) and body mass (d: -0.22, 95% CI: -0.42 to -0.03, P = 0.03) found a significant reduction after exercise compared to controls. Overall, exercise interventions did not modify fasting concentrations of total ghrelin, acylated ghrelin, and PYY in individuals with overweight or obesity, although they reduced body mass and BMI. Thus, any upregulation of appetite and energy intake in individuals with overweight and obesity participating in exercise programmes is unlikely to be related to fasting concentrations of gastrointestinal appetite hormones.
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4.
Influence of water-based exercise on energy intake, appetite, and appetite-related hormones in adults: A systematic review and meta-analysis.
Grigg, MJ, Thake, CD, Allgrove, JE, King, JA, Thackray, AE, Stensel, DJ, Owen, A, Broom, DR
Appetite. 2023;180:106375
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Exercise is an effective way to improve mental and physical health and can influence weight management due to the energy expenditure. Energy balance is influenced by day-to-day variations in energy intake and expenditure. The aim of this study was to address whether water-based exercise influences energy intake, appetite, and appetite related hormones differently to land based exercise in adults. This study is a systematic review and meta-analysis of nine studies which include randomised crossover ( 7 trials), semi-random (1 trial) (water-trial was required prior to iso-energetically matched water trial) and independent group (1 trial) (used in the 12-week study) designs. Results show that post-exercise energy intake is higher after water-based exercise versus a resting control. However, there wasn’t any difference in energy intake when water-based exercise was compared with land-based exercise. Furthermore, when different water temperatures were analysed, post-exercise energy intake was higher in cold water versus neutral water. Additionally, cycling and swimming did not alter fasting plasma concentrations of appetite regulating hormones (ghrelin and leptin), insulin or total peptide YY [gut hormone] but contributed to body mass loss. Authors conclude that if body mass management is a person’s primary focus, it is important to be mindful of the tendency to eat more in the subsequent hours after water-based exercise, as energy intake may be increased when compared to a no exercise control.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The only type of exercise reporting an increase in energy intake was in water-based activities, where the temperature was between 18-20• C. However, this was only when explored in comparison to a resting control. No difference was reported in energy intake when water-based exercise was compared with land-based exercise.
- Any form of exercise, whether land or water-based should be considered where appropriate to reduce the risks of sedentary behaviour.
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:
Exercise is effective for weight-management alongside other physical and mental health benefits. Changes in appetite-regulating hormones may affect energy balance, e.g. some exercise may suppress appetite, known as exercise-induced anorexia. This review evaluated differences in energy intake, appetite and appetite-related hormones in land-based versus water-based exercise.
Methods:
The meta-analysis followed PRISMA guidelines and was registered on PROSPERO. Literature searching resulted in eight studies published between 1991 and 2021, which met the inclusion criteria (water v control), 5 studies (water v land) and 2 studies (water at different temperatures). Risk of Bias was assessed using Cochrane’s Risk of Bias for randomised trials.
Results:
Data were analysed in RevMan 5.4.1 using fixed effects, generic inverse variance method on energy intake. High heterogeneity prevented analysis on appetite and appetite-related hormones. Standard deviation was inputted based on estimated values for missing data. Heterogeneity was calculated using the I2 index. Sensitivity analyses were conducted. Statistical significance was set at p<0.05 and analyses based on two-tailed Z tests.
All participants had a healthy BMI, were aged 19-39 and ranged from well-trained to non-exercisers. A single bout of water-based exercise increased ad-libitum energy intake compared to a non-exercise control (mean difference [95% CI]: 330 [118, 542] kJ, P = 0.002) but no difference was identified between water and land-based exercise (78 [-176, 334] kJ, P = 0.55). Cold water exercise (18–20 •C) increased energy intake more than neutral water (27–33 •C) temperature (719 [222, 1215] kJ; P < 0.005). One 12-week study reported cycling and swimming did not alter fasting plasma concentrations of total ghrelin, insulin, leptin or total PYY but contributed to body mass loss 87.3 (5.2) to 85.9 (5.0) kg and 88.9 (4.9) to 86.4 (4.5) kg (P < 0.05) respectively.
Conclusion:
Despite limitations, this review may provide preliminary evidence on energy intake and appetite for water-based activities. If weight management is a primary focus, then water temperature needs to be considered, particularly if sub 20•C .
Clinical practice applications:
Although this study suggests cold water exercise may cause an increase in energy intake, 95% confidence intervals for individual studies are very large so results should be interpreted cautiously. Those preferring exercise in cold water, should be encouraged, providing they are mindful of the tendency to eat more post-exercise.
It is not possible to draw any robust conclusions about the ratings of hunger in response to different types of exercise due to limited data. However, according to the review, five studies demonstrated that hunger was suppressed more than control prior at the start of water-based exercise, and during and immediately after exercise.
Considerations for future research:
Most participants were of healthy weight and physically active, however since appetite signals may be dysregulated in obesity, including all weight categories and different activity levels may generate a more comprehensive overview.
Further research recommendations include:
- Measuring the effects of water- based activities on appetite, appetite related hormones and energy intake at different time points following exercise in order to provide recommendations for effective weight management strategies and in a range of different temperatures.
- Using a ‘no exercise’ water immersion control. Evidence suggests that immersion in cold water alone may increase energy expenditure
- Evaluating the effect of a water-based activity, such as swimming performed in a ‘fasted’ and ‘non-fasted’ state to investigate the impact on appetite, appetite related hormones and energy intake.
Abstract
Single bouts of land-based exercise suppress appetite and do not typically alter energy intake in the short-term, whereas it has been suggested that water-based exercise may evoke orexigenic effects. The primary aim was to systematically review the available literature investigating the influence of water-based exercise on energy intake in adults (PROSPERO ID number CRD42022314349). PubMed, Medline, Sport-Discus, Academic Search Complete, CINAHL and Public Health Database were searched for peer-reviewed articles published in English from 1900 to May 2022. Included studies implemented a water-based exercise intervention versus a control or comparator. Risk of bias was assessed using the revised Cochrane 'Risk of bias tool for randomised trials' (RoB 2.0). We identified eight acute (same day) exercise studies which met the inclusion criteria. Meta-analysis was performed using a fixed effects generic inverse variance method on energy intake (8 studies (water versus control), 5 studies (water versus land) and 2 studies (water at two different temperatures)). Appetite and appetite-related hormones are also examined but high heterogeneity did not allow a meta-analysis of these outcome measures. We identified one chronic exercise training study which met the inclusion criteria with findings discussed narratively. Meta-analysis revealed that a single bout of exercise in water increased ad-libitum energy intake compared to a non-exercise control (mean difference [95% CI]: 330 [118, 542] kJ, P = 0.002). No difference in ad libitum energy intake was identified between water and land-based exercise (78 [-176, 334] kJ, P = 0.55). Exercising in cold water (18-20 °C) increased energy intake to a greater extent than neutral water (27-33 °C) temperature (719 [222, 1215] kJ; P < 0.005). The one eligible 12-week study did not assess whether water-based exercise influenced energy intake but did find that cycling and swimming did not alter fasting plasma concentrations of total ghrelin, insulin, leptin or total PYY but contributed to body mass loss 87.3 (5.2) to 85.9 (5.0) kg and 88.9 (4.9) to 86.4 (4.5) kg (P < 0.05) respectively. To conclude, if body mass management is a person's primary focus, they should be mindful of the tendency to eat more in the hours after a water-based exercise session, particularly when the water temperature is cold (18-20 °C).
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5.
Low-carbohydrate diets and men's cortisol and testosterone: Systematic review and meta-analysis.
Whittaker, J, Harris, M
Nutrition and health. 2022;28(4):543-554
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Testosterone is the primary male sex hormone, and vital for reproductive development and function. Moreover, low endogenous testosterone is associated with an increased risk of chronic disease, including type 2 diabetes and cardiovascular disease. The aim of this study was to investigate the effects of low- versus high-carbohydrate diets on mens' testosterone and cortisol. This study is a systematic review and meta-analysis of twenty-seven studies with a total of 309 participants. Twelve of these studies were randomised trials whilst the rest were non-randomised. Results show an increase in resting and post-exercise cortisol on short-term low-carbohydrate diets (<3 weeks). In fact, resting cortisol levels return to baseline after <3 weeks on a LC diet, whilst post-exercise cortisol remains elevated. Furthermore, high-protein diets cause a large decrease in resting total testosterone. Authors conclude that further research is required in order to warrant their findings.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Short-term LC-diets diets cause a moderate increase in resting and post-exercise cortisol however this effect is not seen in LC-diets followed for great than 3 weeks
- HP-LC diets caused a statistically significant decrease in resting TT, suggesting caution in relation to endocrine effects of LC diets
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:
A systematic review and network meta-analysis was conducted on the effects of low-carbohydrate (LC) versus high-carbohydrate (HC) diets on men’s testosterone and cortisol.
The review was registered with PROSPERO and reported using PRISMA 2020 checklists.
Methods:
A comprehensive search strategy was used to find intervention studies looking at healthy adult males and LC diets of <35% carbohydrate. Studies were assessed for quality using the Cochrane Risk of Bias tool. Sub-group analyses was conducted for diet duration, protein intake and exercise duration.
Results:
The literature search resulted in 27 studies with a total of 309 healthy adult male participants, age: 27.3 ± 4.7 (to minimise variation in steroid hormone metabolism), body mass: 78.6± 7.1kg and BMI: 24.8 ±1.6. 12 randomised and 15 non-randomised controlled trials were analysed. 21 studies were considered low risk bias, 5 medium and 1 high risk.
- Short-term (<3 weeks) LC diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01) when compared to HC diets.
- Long-term (≥3 weeks) LC diets had no consistent effect on resting cortisol
- LC diets resulted in higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01).
- The overall results for resting total testosterone (TT) showed a significant decrease on LC versus HC diets (SMD = −0.48, p = 0.01. However, subgroup analyses revealed this effect to be limited to high-protein (HP) LC diets, which yielded a very large decrease in TT (SMD = −1.08, p < 0.01; ∼5.23 nmol/L), albeit in a small sample (n = 26).
- Moderate protein (MP) (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (−1.08 [−1.67, −0.48], p < 0.01) and post-exercise total testosterone (−1.01 [−2, −0.01] p = 0.05).
- There was no overall effect of LC versus HC diets on 0 h post-exercise TT (SMD = −0.03, p = 0.95). However, subgroup analysis showed 0 h post-exercise was non-significantly higher on long-term LC versus HC diets (SMD = 0.44, p = 0.18), and much lower on short-term LC versus HC diets (SMD = −1.01, p = 0.05)
Conclusion:
This systematic review and metanalysis found an increase in resting and post-exercise cortisol on short-term LC diets. Cortisol does return to baseline in the first 3 weeks of a low-carbohydrate (LC) diet. The same response is, however, not seen in post-exercise cortisol, which remains elevated. In addition, the review showed that compared to moderate-protein diets, HP diets were found to cause a large decrease in resting and post-exercise TT (∼5.23 nmol/L).
Clinical practice applications:
The results of this review suggest that exercising whilst following a LC diet can increase cortisol in the short term, but not long-term. This suggests a period of diet adaptation. The effects of long-term LC diets on cardiovascular disease risk is uncertain and healthcare practitioners should monitor client responses and keep up-to-date with new research in this area
Since HP-LC diets were found to significantly decrease resting testosterone it highlights the need to ensure that protein intake does not exceed the urea cycle’s capacity due to potential adverse endocrine effects.
For clients where there is a desire to increase strength, power and hypertrophy, a MP-LC diet could be of benefit, as it showed potential to signal an increased anabolic state post exercise..
NB: Since the review only included a low number of studies and saw within these some heterogeneity that could not be explained, more research is needed before the paper’s findings can be conclusive. The above potential practice applications should therefore be seen as something to be mindful of when working with clients where cortisol and testosterone levels are relevant to their protocol.
Considerations for future research:
Future research should consider:
- Since LC diets have been shown to have a positive effect on health – decreased triglycerides, increased high density lipoprotein cholesterol and weight loss - future studies would benefit from including these markers so any positive and negative impacts can be monitored directly.
- Despite extensive analysis including sensitivity analysis to reduce bias and heterogeneity of the results, the paper highlights a need for further research to ensure consistency in key parameters e.g., exercise duration and intensity, carbohydrate supplements inclusion and period of dietary intervention. Since it was identified that HP-LP diets impact post exercise and resting TT, follow up studies would benefit from consistency in participants diets. This would help to reduce any potential confounding results.
Abstract
Background: Low-carbohydrate diets may have endocrine effects, although individual studies are conflicting. Therefore, a review was conducted on the effects of low- versus high-carbohydrate diets on men's testosterone and cortisol. Methods: The review was registered on PROSPERO (CRD42021255957). The inclusion criteria were: intervention study, healthy adult males, and low-carbohydrate diet: ≤35% carbohydrate. Eight databases were searched from conception to May 2021. Cochrane's risk of bias tool was used for quality assessment. Random-effects, meta-analyses using standardized mean differences and 95% confidence intervals, were performed with Review Manager. Subgroup analyses were conducted for diet duration, protein intake, and exercise duration. Results: Twenty-seven studies were included, with a total of 309 participants. Short-term (<3 weeks), low- versus high-carbohydrate diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01). Whereas, long-term (≥3 weeks), low-carbohydrate diets had no consistent effect on resting cortisol. Low- versus high-carbohydrate diets resulted in much higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01). Moderate-protein (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (-1.08 [-1.67, -0.48], p < 0.01) and post-exercise total testosterone (-1.01 [-2, -0.01] p = 0.05). Conclusions: Resting and post-exercise cortisol increase during the first 3 weeks of a low-carbohydrate diet. Afterwards, resting cortisol appears to return to baseline, whilst post-exercise cortisol remains elevated. High-protein diets cause a large decrease in resting total testosterone (∼5.23 nmol/L).
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6.
Effectiveness of Exercise Training on Male Factor Infertility: A Systematic Review and Network Meta-analysis.
Hajizadeh Maleki, B, Tartibian, B, Chehrazi, M
Sports health. 2022;14(4):508-517
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Male factor infertility is characterised by the existence of suboptimal sperm parameters in the male partner of childbearing age and is presently defined as the inability to conceive a child with frequent and unprotected sexual intercourse in the fertile phase of the menstrual cycles for a year or longer. The main aim of this study was to evaluate the effectiveness of 1 or more of the selected types of exercise interventions (moderate-intensity continuous training (MICT), resistance training (RT), combined aerobic and resistance training (CET), high-intensity continuous training (HICT), and high-intensity interval training (HIIT)) in the prevention and treatment of male factor infertility. This study is a systematic review and meta-analysis of seven randomised controlled trials representing 18 groups (11 exercise, 7 non-intervention control [NON-EX]) and 2641 participants and/or patients (1429 exercise, 1212 NON-EX). Results show that in the setting of couples with male factor infertility, when compared with the NON-EX group, selected types of exercise interventions improved the relative risk of pregnancy rate in the following order: CET > MICT > RT > HICT > HIIT. The top-ranking interventions for live birth rate were for MICT, RT, HIIT, CET, and HICT. In addition, the interventions with the highest probability of being the best approach out of all available options in improving semen quality parameters were for CET, MICT, HICT, RT, and HIIT. Authors conclude that when clinicians are formulating clinical recommendations for preventing and treating male factor infertility, the findings of this study should be considered.
Expert Review
Conflicts of interest:
None
Take Home Message:
- For couples with male factor infertility, this review recommends moderate intensity-aerobic exercise in combination with strength training to be the intervention with the highest probability of being the best approach for reproductive health benefits.
- A conservative interpretation of the findings is required because they were based on single studies.
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
The World Health Organisation estimates that infertility affects 10% to 15% of couples in industrialised countries. Approximately 50% of all infertility cases are attributed to male-related factors, in particular, poor semen quality (called male factor infertility). The aim of this study was to evaluate the effectiveness of exercise training on male factor infertility and seminal markers of inflammation.
Methods
This is the first study to undertake a systematic review with network meta-analysis of 7 RCTs to evaluate the effectiveness of 1 or more types of exercise interventions on male factor infertility and seminal markers of inflammation, as well as to provide clinicians with a ranking of treatments to inform them of the treatment effects of exercise training and physical activity.
The forms of exercise include: moderate-intensity continuous training (MICT), resistance training (RT), combined aerobic and resistance training (CET), high-intensity continuous training (HICT), and high-intensity interval training (HIIT).
7 RCTs representing 18 groups (11 exercise (supervised, not home-based), 7 non-intervention control [NON-EX]) and 2641 participants and/or patients (1429 exercise, 1212 NON-EX). All the RCTs were conducted in Iran involving healthy adult participants and/or infertile patients (with doctor-diagnosed male factor infertility). The intervention period was ≥10 weeks with a follow-up period.
None of the studies reported changes in either patients’ dietary intakes or normal daily physical activities and lifestyles during the intervention period.
Results
Compared with a non-intervention control group, the top ranking interventions:
For pregnancy rate:
Combined aerobic and resistance training (CET) (p= 0.89 relative risk [RR] = 27.81), moderate-intensity continuous training (MICT) (p=0.87, RR = 26.67), resistance training (RT) (p=0.61,RR = 12.54), high intensity continuous training (HICT) (p=0.34, RR = 5.55), and high-intensity interval training (HIIT) (p=0.28, RR = 4.63).
For live birth rate:
MICT (p=0.82, RR = 10.05), RT (p=0.70, RR = 4.92), HIIT (p=0.66, RR = 4.38)), CET (p=0.45, RR = 2.20), and HICT (p=0.30, RR = 1.55)
The following parameters/markers rank the 5 exercise strategies in order of effectiveness:
- Semen quality parameters were significantly improved after the following types of exercise interventions as compared with the non-intervention group [NON-EX]: CET > MICT > HICT > RT > HIIT
- The following training strategies were significantly better at improving seminal markers of oxidative stress: CET > MICT > HIIT > HICT > RT
- The following training strategies were significantly better at improving seminal markers of inflammation: CET > MICT > HIIT > RT > HICT
- The following training strategies were significantly better at improving measures of body composition and VO2 max: CET > HICT > MICT > HIIT > RT
- There was insufficient evidence of a difference for the selected types of exercise interventions versus NON-EX group for pregnancy and live birth rates in healthy participants.
Conclusion
Combined aerobic and resistance training (CET) was found to be the intervention with the highest probability of being the best approach for improving the male factor infertility.
Clinical practice applications:
- In light of these findings, it is reasonable to propose that infertile men and at-risk populations take part in the top-ranking interventions identified in this analysis.
- For substantial reproductive health benefits, one should consider doing all of the selected types of exercise interventions (CET, MICT, RT, HICT, and HIIT); however, moderate intensity-aerobic exercise and strength training in combination would generally be more favourable to lend clinically significant improvements.
- To add to this, exercise can offer a myriad of other health benefits, is a possibly safe activity and a cost-effective treatment strategy for male factor infertility.
Considerations for future research:
- There was only a small number of relevant trials available for comparison suggesting the need for additional study in this field.
- Further trials are needed to analyse the dose-response impacts of exercise modalities on male reproductive function.
- The results propose several domains for development in the reporting of RCTs addressing the impacts of interventional exercise studies on male reproductive function.
- Heterogeneity of some findings and discrepancy across the included studies was significant. For example, variations in the characteristics of training programs. Future analyses should aim to continue to address this.
- There is a concern that this study may not relate to already active patients with male factor infertility which future studies should address.
Abstract
CONTEXT Mounting evidence from the literature suggests that different types of training interventions can be successful at improving several aspects of male reproductive function in both fertile and infertile populations. OBJECTIVE The aim of this study was to evaluate the effectiveness of exercise training on male factor infertility and seminal markers of inflammation. DATA SOURCES We searched PubMed, CISCOM, Springer, Elsevier Science, Cochrane Central Register of Controlled Trials, Scopus, PEDro, Ovid (Medline, EMBASE, PsycINFO), Sport Discus, Orbis, CINAHL, Web of Science, ProQuest, and the ClinicalTrials.gov registry for randomized controlled trials (RCTs) that analyzed the impacts of selected types of exercise interventions on markers of male reproductive function and reproductive performance. STUDY SELECTION A total of 336 records were identified, of which we included 7 trials reporting on 2641 fertile and infertile men in the systematic review and network meta-analysis. LEVEL OF EVIDENCE Level 1 (because this is a systematic review of RCTs). DATA EXTRACTION The data included the study design, participant characteristics, inclusion and exclusion, intervention characteristics, outcome measures, and the main results of the study. RESULTS The results of network meta-analysis showed that, compared with a nonintervention control group, the top-ranking interventions for pregnancy rate were for combined aerobic and resistance training (CET) (relative risk [RR] = 27.81), moderate-intensity continuous training (MICT) (RR = 26.67), resistance training (RT) (RR = 12.54), high-intensity continuous training (HICT) (RR = 5.55), and high-intensity interval training (HIIT) (RR = 4.63). While the top-ranking interventions for live birth rate were for MICT (RR = 10.05), RT (RR = 4.92), HIIT (RR = 4.38), CET (RR = 2.20), and HICT (RR = 1.55). Also, with the following order of effectiveness, 5 training strategies were significantly better at improving semen quality parameters (CET > MICT > HICT > RT > HIIT), seminal markers of oxidative stress (CET > MICT > HIIT > HICT > RT), seminal markers of inflammation (CET > MICT > HIIT > RT > HICT), as well as measures of body composition and VO2max (CET > HICT > MICT > HIIT > RT). CONCLUSION The review recommends that the intervention with the highest probability of being the best approach out of all available options for improving the male factor infertility was for CET.
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7.
The effect of healthy dietary patterns on male semen quality: a systematic review and meta-analysis.
Cao, LL, Chang, JJ, Wang, SJ, Li, YH, Yuan, MY, Wang, GF, Su, PY
Asian journal of andrology. 2022;24(5):549-557
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Infertility has been identified by the World Health Organization as a worldwide problem. The analysis of semen quality is key in assessing male fertility. The aim of this study was to explore the effect of healthy dietary patterns on male semen quality. This study is a systematic review and meta-analysis of six articles. The six articles were cross-sectional studies involving 1244 subjects, however, 708 subjects with the lowest and highest adherence to a healthy dietary pattern were included in the meta-analysis. Results show that the sperm concentration, progressive sperm motility, and total sperm count were significantly higher in the group with high consumption of a healthy dietary pattern than those in the group with low consumption; however, there wasn’t a clear relationship between normal sperm morphology, total sperm motility, and semen volume. Authors conclude that dietary interventions should be considered in clinical work as part of the therapies improving male semen quality.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This Systematic Review and Meta Analysis showed that healthy dietary patterns had beneficial effects on sperm concentration, total sperm count, and progressive sperm motility in males, which affect male fertility.
- Authors concluded that healthy dietary patterns may promote male reproductive health and thus improve semen quality in the population.
- Healthy dietary patterns meant the Mediterranean diet for 4 out of 6 studies. All healthy diet patterns were determined by the authors to be rich in plant-based foods, where saturated fats provide only a small percentage of the total energy intake.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
- This study aimed to determine the effects of healthy dietary patterns on semen quality.
Methodology
- This meta-analysis was performed following PRISMA guidelines and included 6 cross-sectional studies with 1244 participants
- The included cross-sectional studies examined the influence of the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and prudent diet patterns on semen quality parameters.
- In 4 of the studies participants were divided into groups based on their scores for the Mediterranean diet from low to high adherence.
- 2 studies examined the DASH diet and the prudent diet and used food frequency questionnaires to compare high consumption with low consumption of healthy dietary patterns.
- The PICOS (Participants, Intervention, Comparison, Outcomes, and Study design) criteria that were used to structure the research question.
- 11 Checklists were used to assess the quality of included studies.
Results:
By comparing high consumption with low consumption of healthy dietary patterns, the results of the meta-analysis showed:
- significantly higher sperm concentrations (mean difference [MD] = 6.88 × 106 ml−1, 95% confidence interval [CI]: 1.26 × 106 ml−1–12.49 × 106 ml−1; P < 0.05)
- significant increase in total sperm count (MD = 16.70 × 106, 95% CI: 2.37 × 106–31.03 × 106; P < 0.05)
- significant increase in progressive sperm motility (MD = 5.85%, 95% CI: 2.59%–9.12%; P < 0.01) but there was no significant correlation between healthy dietary patterns and total sperm motility (MD: 6.86%, 95% CI: −0.25%–13.96%; P > 0.05).
- there was no significant association between a healthy dietary pattern and normal sperm morphology (MD: 0.28%, 95% CI: −0.33%–0.90%; P > 0.05)
- there was no significant association between a healthy dietary pattern and semen volume (MD: 0.04 ml, 95% CI: −0.20 ml–0.28 ml; P > 0.05).
Limitations:
- Included studies were all cross-sectional studies, and it is impossible to determine the causal relationship between the high intake of healthy dietary patterns and semen quality.
- The number of studies included was small, and there was not enough literature to support authors in drawing reliable conclusions.
- No comparison was made between specific diets such as dash vs Mediterranean.
Clinical practice applications:
- The authors concluded that dietary interventions should be considered in clinical work as part of the therapies improving male semen quality.
- Dietary interventions for men should be included as part of preconceptional clinical management,
- Dietary interventions for men should also be considered in infertility clinical management.
Considerations for future research:
- Randomised Clinical Trials should be conducted to build on these findings.
Abstract
The incidence of infertility has recently risen. Semen quality is an important male fertility indicator, and dietary factors can affect semen quality. We conducted this systematic review and meta-analysis to determine the effects of healthy dietary patterns on semen quality. A literature search was conducted in 3 databases (Embase, Web of Science and PubMed) on August 21, 2021. The included cross-sectional studies examined the influence of the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and prudent diet patterns on semen quality parameters; six studies (1244 subjects) were included. By comparing high consumption with low consumption of healthy dietary patterns, the results of the meta-analysis showed significantly higher sperm concentrations (mean difference [MD] = 6.88 × 106 ml-1, 95% confidence interval [CI]: 1.26 × 106 ml-1-12.49 × 106 ml-1; P < 0.05), a significant increase in total sperm count (MD = 16.70 × 106, 95% CI: 2.37 × 106-31.03 × 106; P < 0.05), and a significant increase in progressive sperm motility (MD = 5.85%, 95% CI: 2.59%-9.12%; P < 0.01). The sperm concentration, progressive sperm motility, and total sperm count were significantly higher in men with higher versus lower consumption of healthy dietary patterns. However, the results must be interpreted with caution.
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8.
Cadmium exposure and risk of diabetes and prediabetes: A systematic review and dose-response meta-analysis.
Filippini, T, Wise, LA, Vinceti, M
Environment international. 2022;158:106920
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Cadmium is a toxic metal released in the environment after both natural and anthropogenic activities, particularly in contaminated and industrial areas devoted to smelting and refining of metals, and the manufacturing of batteries, coatings, or plastics. Exposure to cadmium may occur through occupational activities, smoking, food, and air pollution. The aim of this study was to provide updated literature on cadmium exposure and the risk of both type 2 diabetes and prediabetes, and to model the shape of these associations using a dose response approach. This study is a systematic review and meta-analysis of forty-two studies. Diabetes was investigated as an outcome in thirty-one studies, prediabetes in four studies, and both diabetes and prediabetes in seven studies. Results show that higher cadmium exposure was associated with increased risks of both diabetes and prediabetes. Diabetes risk increased linearly in studies using urinary cadmium concentrations, while disease risk increased only at the highest exposure levels when assessed using blood concentrations. The analysis for prediabetes also showed a linear increase in risk from low exposure, with a flattening effect at higher urinary cadmium concentrations. Authors conclude that their findings add to the available evidence on potential adverse health effects of environmental exposure to cadmium.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Cadmium exposure through diet, occupational exposure and smoking may increase the risk of type 2 diabetes in affected individuals.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
Cadmium exposure might occur through occupational activities, food, air pollution, and smoking. Smokers, in particular, have higher blood cadmium concentrations than non-smokers. Food is the main transmission route for non-smokers, particularly cereals, vegetables, mollusks, and offal. Females and older adults are at a greater risk due to an increased risk of iron deficiency in these population groups, leading to increased absorption, as well as greater age-related bioaccumulation.
Furthermore, cadmium exposure has been associated with an increased risk of diabetes in a number of studies, as referenced in the present manuscript. However, the magnitude and shape of the correlation are uncertain.This systematic review and meta-analysis therefore investigates the relationship between exposure to cadmium and type 2 diabetes and prediabetes risk.
Methods
- The systematic review was conducted and reported in line with the PRISMA 2020 statement. Search strings related to the terms “cadmium” and “diabetes”, or “prediabetes state” in PubMed/MEDLINE, Web of Science and EMBASE databases were employed to search for relevant articles. Latest search date: 1 October 2021.
- Eligibility criteria included: studies evaluating cadmium exposure via biomarker levels with outcomes of interest being type 2 diabetes or prediabetes using WHO criteria and the American Diabetes Association; and reporting of relative risk estimates using the hazard ratio (HR), risk ratio (RR), or odds ratio (OR) with the corresponding 95% confidence interval (CIs). For inclusion in dose-response meta-analysis: reported effect estimates for all exposure categories along with dose in each category.
- Studies were assessed for risk of bias using theROBINS-E tool. Overall certainty of the evidence was assessed using the GRADE approach.
- The meta-analysis involved estimating RRs with corresponding 95% CIs from each study. Generalised least-squares regression with a random effects model and restricted maximum likelihood estimation were used. The highest versus lowest exposure categories were compared. The association between exposure and risk of diabetes or prediabetes was investigated using a one-stage dose-response meta-analysis. Sensitivity analyses were performed and heterogeneity between studies was assessed..
Results
- 42 eligible studies (case-control, cross-sectional, and cohort studies), ranging 65-34, 814 male and female adult participants, were identified investigating the association between cadmium exposure and risk of diabetes or prediabetes. Seven of the included studies were at overall high risk of bias; heterogeneity in the resulting meta-analyses was moderate to substantial. Sensitivity analyses indicated comparable results. Assessment with GRADE found no major inconsistency, indirectness or imprecision for either outcome.
- Comparing the highest versus lowest cadmium exposure concentrations associated with type 2 diabetes resulted in a RR of 1.24 (95% CI 0.96–1.59), RR 1.21 (CI 95% 1.00–1.45), and RR 1.47 (CI 95% 1.01–2.13) for blood, urinary, and toenail matrices, respectively. Concurrently, there was an elevated risk of prediabetes for cadmium levels in urine of RR 1.41 (95% CI: 1.15–1.73) and blood RR 1.38 (95% CI: 1.16–1.63), respectively.
- In the dose-response meta-analysis, a linear positive correlation between increasing urinary cadmium levels and diabetes risk was observed, with a RR 1.25 (95% CI 0.90–1.72) at concentration 2.0 µg/g of creatinine compared with no exposure. Conversely, for blood cadmium concentrations, the diabetes risk seemed to rise above 1 µg/L compared with no exposure. Moreover, prediabetes risk increased up to approximately 2 µg/g creatinine beyond which a plateau was reached with RR 1.40 (95% CI 1.12–1.76) at 2 µg/g creatinine.
- The meta-regression showed a negligible correlation between blood cadmium levels and diabetes risk. However, a positive yet imprecise association was found with increasing urinary cadmium concentrations. Similarly, no association was observed between blood cadmium concentrations and risk of prediabetes, whereas a positive relationship with urinary cadmium levels was observed. However, these findings were based on a limited cohort of studies.
Conclusions
- A positive linear correlation between cadmium concentration (measured in multiple matrices) and risk of both type 2 diabetes and prediabetes with a dose-response relationship (moderate-certainty evidence) were observed in this systematic review and meta-analysis. Diabetes risk increased linearly in studies using urinary cadmium concentrations, whereas disease risk increased only at the highest exposure levels when assessed using blood levels. The analysis for prediabetes also demonstrated a linear increase in risk from low exposure, which plateaued at higher urinary cadmium concentrations.
Clinical practice applications:
- To inform practitioners and clients of the risks of cadmium exposure in the diet, through occupational exposure, and through smoking.
- To motivate practitioners to educate themselves and their clients regarding the foods which may pose a higher risk of cadmium exposure (not reviewed in the present article).
- To advise clients on prediabetes and type 2 diabetes risk from cadmium exposure through smoking.
Considerations for future research:
- As cited by the authors, future studies could incorporate stratified analysis in specific subgroups, e.g., non-smokers, or could be restricted to prospective cohort studies with more sufficient data,
- Large-scale observational studies could be conducted investigating cadmium exposure in smokers versus non-smokers.
- Clinical trials could be performed to evaluate the effect of reduction or cessation of tobacco smoking on total body cadmium concentrations .
- Continuous surveillance of dietary cadmium exposure and other heavy metals should be prioritised to inform public health.
- Dietary interventions could assess the possibility to attenuate the risk of cadmium exposure.
Abstract
BACKGROUND Cadmium exposure has been associated with increased diabetes risk in several studies, though there is still considerable debate about the magnitude and shape of the association. OBJECTIVE To perform a systematic review and meta-analysis of observational studies investigating the relation between cadmium exposure and risk of type 2 diabetes and prediabetes, and to summarize data on the magnitude and shape of the association. DATA SOURCE After conducting an online literature search through October 1, 2021, we identified 42 eligible studies investigating the association between cadmium exposure and risk of diabetes and prediabetes. STUDY ELIGIBILITY CRITERIA We included studies that assessed cadmium exposure through biomarker levels; examined type 2 diabetes or prediabetes among outcomes; and reported effect estimates for cadmium exposure for meta-analysis only. STUDY APPRAISAL AND SYNTHESIS METHODS Studies were evaluated using ROBINS-E risk of bias tool. We quantitively assessed the relation between exposure and study outcomes using one-stage dose-response meta-analysis with a random effects meta-analytical model. RESULTS In the meta-analysis, comparing highest-versus-lowest cadmium exposure levels, summary relative risks (RRs) for type 2 diabetes were 1.24 (95% confidence interval 0.96-1.59), 1.21 (1.00-1.45), and 1.47 (1.01-2.13) for blood, urinary, and toenail matrices, respectively. Similarly, there was an increased risk of prediabetes for cadmium concentrations in both urine (RR = 1.41, 95% CI: 1.15-1.73) and blood (RR = 1.38, 95% CI: 1.16-1.63). In the dose-response meta-analysis, we observed a consistent linear positive association between cadmium exposure and diabetes risk, with RRs of 1.25 (0.90-1.72) at 2.0 µg/g of creatinine. Conversely for blood cadmium, diabetes risk appeared to increase only above 1 µg/L. Prediabetes risk increased up to approximately 2 µg/g creatinine above which it reached a plateau with RR of 1.42 (1.12-1.76) at 2 µg/g creatinine. LIMITATIONS AND CONCLUSIONS This analysis provides moderate-certainty evidence for a positive association between cadmium exposure (measured in multiple matrices) and risk of both diabetes and prediabetes.
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9.
Consumption of flavonoids and risk of hormone-related cancers: a systematic review and meta-analysis of observational studies.
Liu, F, Peng, Y, Qiao, Y, Huang, Y, Song, F, Zhang, M, Song, F
Nutrition journal. 2022;21(1):27
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Hormone-related cancers (HRCs) are greatly influenced by hormone levels and generally respond to hormone regulation, which plays an indispensable role in tumour growth. Encouragingly, diets rich in vegetables, fruits and tea are found to reduce the cancer risk, having the potential to exert chemo-preventive effects with the presence of anticarcinogenic phytochemicals. The aim of this study was to elucidate the association between flavonoids intake and HRCs risk. This study is a meta-analysis of fifty-one studies. It consisted of 22 prospective cohort studies, 1 nested case–control study, 18 population-based case–control studies and 10 hospital-based case–control studies. Results show that higher consumption of total flavonoids was only associated with an increased risk of men-specific cancers, mainly prostate cancer. Furthermore, the subclasses, flavanols, flavones, and isoflavones, and the three main individual compounds of isoflavones (daidzein, genistein and glycitein) may have protective effects on women-specific cancers, whereas flavones and flavanones have been found to cause potentially dangerous effects in thyroid cancer. Additionally, there was no evidence in support of any role for anthocyanidins in HRCs. Authors conclude that there is a small amount of evidence that total flavonoids, flavanols, flavones, flavanones, flavan-3-ols and isoflavones may be associated with a lower or higher risk of certain HRCs, which may provide guidance for dietary guidelines to a certain extent in the future.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Dietary flavonoids are widely available in plant-based foods such as vegetables, citrus fruits, green tea and berries
- Menopausal status may be an important consideration for flavonoid intake when considering breast cancer risk
- Differences in results for Asians and non-Asians need to be considered for the use of flavonoids in women-specific hormonal cancers and prostate cancer in men
- Caution should be exercised when considering flavones and flavanones and thyroid cancer risk until further research is available
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
Hormone-related cancers (HRCs) are the most frequently diagnosed cancers globally , accounting for more than a quarter of new cancer cases worldwide in 2018. They include breast, ovarian, endometrial, prostate, testicular and thyroid cancer which share a similar carcinogenic mechanism. Diets rich in vegetables, fruit, legumes and tea may reduce cancer risk due to anticarcinogenic phytochemicals, such as flavonoids. Flavonoids are claimed to have many different physiological and pathological functions in the cancer process, including tumour cell proliferation, inflammation, angiogenesis, invasion and metastasis.. This study aimed to summarise the relationships between consumption of flavonoids with the risk of HRC.
Methods:
The meta-analysis was carried out following PRISMA guidelines and registered on PROSPERO. A literature search in PubMed and Embase was conducted using the keywords flavonoids, flavanols and isoflavones and breast, ovarian, endometrial, prostate, testicular and thyroid cancer. 51 studies published between 1999 and 2022 consisted of 22 prospective cohort, 18 population-based and 10 hospital-based case-control studies. On the Newcastle-Ottawa Scale assessment all studies were of medium or high methodological quality.
Results:
Results were analysed using Stata 15.1 software and ORs with 95% CIs used to measure the association between flavonoid intake and HRCs risk. Statistical I2 evaluated heterogeneity among the studies.
Funnel plots were inspected for publication bias and calculated by Begg’s/Egger’s regression tests. Sensitivity analyses were performed to explore the source of heterogeneity. Subgroup analysis was performed on study design and region, as well as menopausal status.
Higher consumption of flavonoids was associated with a decreased risk of women-specific cancers but a significant elevated risk of prostate cancer as seen below.
Women specific cancers:
For flavonoid sub-classes, higher consumption of flavanols (OR=0.85; 95% CI, 0.76–0.94; I2=75.5%; p<0.001), flavones (OR=0.85; 95% CI, 0.77–0.95; I2=76.3%; p<0.001) and isoflavones (OR=0.87; 95% CI, 0.82–0.92; I2=73.8%; p<0.001) was associated with a decreased risk of women-specific cancers (breast, ovarian and endometrial), especially among the case–control studies. Similar results were seen in the main compounds of isoflavones: daidzen, genistein and glycitein. There were differences in the association between isoflavones in Asian and non-Asian regions.
Men-specific cancers:
The higher consumption of total flavonoids (OR=1.11; 95% CI, 1.02–1.21; I2 = 0%; p = 0.484) was associated with an increased risk of prostate cancer and this was only found in non-Asian populations.
Conclusion:
Despite limitations of the meta-analysis, such as the use of observational studies and small sample sizes of the included studies, this systematic review may provide some preliminary dietary evidence for the use of flavonoids in HRCs.
Clinical practice applications:
- The promotion of a plant-based diet, rich in vegetables, fruits, green tea and legumes may have protective effects on women-specific cancers due to the rich presence of flavanols, flavones and isoflavones, as well as the compounds genistein, glycitein and daidzein.
- Results show no associations between total flavonoids intake and women-specific cancer however, the sub-groups of flavanols, flavones and isoflavones were associated with a decreased risk in women-specific cancers. Similar results were seen in the individual compounds of isoflavones: genistein, glycitein and daidzein. These results may guide decision-making when recommending the inclusion of these compounds for protective benefits in women-specific cancers.
- The positive association between total flavonoids and prostate cancer risk was only seen in non-Asians, and between higher consumption of flavones and flavanones and thyroid cancer risk albeit in limited studies (n=3) may provide important guidelines when considering which foods to include from a plant-based diet.
Considerations for future research:
- Further meta-analysis of prospective studies with larger sample sizes
- The use of a validated and reliable questionnaire for measuring flavonoid intake
- Intervention studies evaluating flavonoid subclasses
- Comparisons between Asian and non-Asian populations
- Consideration of menopausal status as an effect modifier
Abstract
BACKGROUND Flavonoids seem to have hormone-like and anti-hormone properties so that the consumption of flavonoids may have potential effects on hormone-related cancers (HRCs), but the findings have been inconsistent so far. This meta-analysis was aimed to explore the association between flavonoids intake and HRCs risk among observational studies. METHODS Qualified articles, published on PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) from January 1999 to March 2022 and focused on relationships between flavonoids (total, subclass of and individual flavonoids) and HRCs (breast, ovarian, endometrial, thyroid, prostate and testicular cancer), were retrieved for pooled analysis. Random effects models were performed to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Funnel plots and Begg's/Egger's test were used to evaluate the publication bias. Subgroup analyses and sensitivity analyses were conducted to explore the origins of heterogeneity. RESULTS All included studies were rated as medium or high quality. Higher consumption of flavonols (OR = 0.85, 95% CI: 0.76-0.94), flavones (OR = 0.85, 95% CI: 0.77-0.95) and isoflavones (OR = 0.87, 95% CI: 0.82-0.92) was associated with a decreased risk of women-specific cancers (breast, ovarian and endometrial cancer), while the higher intake of total flavonoids was linked to a significantly elevated risk of prostate cancer (OR = 1.11, 95% CI: 1.02-1.21). A little evidence implied that thyroid cancer risk was augmented with the higher intake of flavones (OR = 1.24, 95% CI: 1.03-1.50) and flavanones (OR = 1.31, 95% CI: 1.09-1.57). CONCLUSIONS The present study suggests evidence that intake of total flavonoids, flavonols, flavones, flavanones, flavan-3-ols and isoflavones would be associated with a lower or higher risk of HRCs, which perhaps provides guidance for diet guidelines to a certain extent. TRIAL REGISTRATION This protocol has been registered on PROSPERO with registration number CRD42020200720 .
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10.
Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data.
Goldenberg, JZ, Day, A, Brinkworth, GD, Sato, J, Yamada, S, Jönsson, T, Beardsley, J, Johnson, JA, Thabane, L, Johnston, BC
BMJ (Clinical research ed.). 2021;372:m4743
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Plain language summary
Diet modification has long been recognised as a component for the treatment of diabetes. Diets low in carbohydrates have been extensively researched, as a diet for those with Type 2 Diabetes (T2D). This systematic review and meta-analysis aimed to determine the effect of low carbohydrate diets on T2D. The systematic review found 23 studies, including 1357 individuals, investigating the role of low carbohydrate diets on T2D outcomes. Low carbohydrate diet was defined as less than 130g of carbohydrate (less than 26% of calories from carbohydrate) for at least 12 weeks. Results reported at 6 months, found low carbohydrate diets were more effective than a normal diet at achieving diabetes remission. However, this effect diminished at 12 months, although longer term improvements were seen in blood lipids, weight loss and measures of prediabetes. It was concluded that individuals with T2D, eating a low carbohydrate diet for 6 months may reverse the disease. This study could be used by healthcare professionals to recommend a short-term low carbohydrate diet to individuals with T2D, to improve their chance of going into remission.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Type 2 diabetes remains a significant and worsening problem worldwide, despite many pharmaceutical developments and a global emphasis on glycemic control.
- This review highlights structured LCDs as a worthwhile option for the management and treatment of diabetes, providing an opportunity for Nutritional Therapy Practitioners to support clients in adopting evidence-informed, modifiable dietary and lifestyle changes for Type Two Diabetes.
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:
- Type 2 diabetes is the most common form of diabetes, accounting for 90-95% of cases.
- Previous randomised trials assessed low carbohydrate diets (LCDs) (<26-45% of daily calories from carbohydrate) as encouraging to improve blood glucose control and outcomes of type 2 diabetes but did not systematically assessed remission of diabetes using low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes.
- Systematic reviews (SR) and meta-analyses represent the most valuable, reliable, and objective tool to summarise evidence from primary studies.
- This SR assessed 23 randomised controlled trials comparing LCDs with mostly low fat control diets in individuals / subjects / participants with type 2 diabetes. LCDs were defined as diets with less than 130 g/day or less than 26% of calories from carbohydrates, based on 2000 kcal/day. The authors used the Cochrane Risk of Bias tool 2.0 (RoB 2) to assess methodological quality of evidence, GRADE to assess the certainty of evidence
- On the basis of assessment of moderate to low certainty evidence, individuals / subjects / participants adhering to a LCD for six months may experience remission of type 2 diabetes without adverse consequences.
- Primary outcomes of interest were remission of type 2 diabetes (dichotomously defined as HbA1c <6.5% or fasting glucose <7.0 mmol/L), with or without the use of diabetes medication.
- Eight studies reported on remission of diabetes at six months. Pooled analysis showed that when remission was defined by an HbA1c level below 6.5% independent of medication use, LCDs increased remissions by an additional 32 per 100 patients followed (risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264; GRADE=moderate)
- When remission was defined by an HbA1c level below 6.5% and the absence of diabetes medication, LCDs increased remissions at a lower rate (risk difference 0.05, –0.05 to 0.14; 5 studies, n=199; GRADE=low)
- Additional primary outcomes were weight loss, HbA1c:
- 18 studies reported on Weight loss results (mean difference –3.46, 95% confidence interval –5.25 to –1.67; n=882 (note that positive results not sustained at 12 mo)
- Seventeen studies reported on HbA1c levels at six months, LCDs achieved greater reductions in HbA1c than did control diets (mean difference –0.47%, –0.60 to –0.34; n=747
- Limitations of study: 1) the definition of remission of diabetes, 2) Self-reported dietary intake data are prone to measurement error, particularly in dietary trials in which participants are not blinded
- This SR was funded in part by Texas A&M University.
- The authors declared no conflicts of interest.
Clinical practice applications:
The Authors highlight LCD diets incorporating carbohydrate of less than 130 g/day or less than 26% of calories (based on 2000 kcal/day) may be a safe strategy to help individuals with type 2 diabetes achieve weight loss and better blood glucose control over a six-month period. Results may not be sustained at 12 months.
Considerations for future research:
- The definition of diabetes remission needs clarification, especially with regard to threshold concentrations of Hb1Ac or fasting glucose and the use of diabetes medication.
- Safety concerns have been raised with LCDs. Although no significant or clinically important increase in total or serious adverse events was identified in this SR, these outcomes should be reported in future trials to confirm the certainty of evidence for safety.
- The Authors suggest long term, well designed, calorie controlled randomised trials are needed to determine the effects of LCD on sustained weight loss and remission of diabetes.
- Larger treatment effects for LCDs in shorter term trials (3 to <6 months), may be trialed as an effect modifier
Abstract
OBJECTIVE To determine the efficacy and safety of low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes. DESIGN Systematic review and meta-analysis. DATA SOURCES Searches of CENTRAL, Medline, Embase, CINAHL, CAB, and grey literature sources from inception to 25 August 2020. STUDY SELECTION Randomized clinical trials evaluating LCDs (<130 g/day or <26% of a 2000 kcal/day diet) and VLCDs (<10% calories from carbohydrates) for at least 12 weeks in adults with type 2 diabetes were eligible. DATA EXTRACTION Primary outcomes were remission of diabetes (HbA1c <6.5% or fasting glucose <7.0 mmol/L, with or without the use of diabetes medication), weight loss, HbA1c, fasting glucose, and adverse events. Secondary outcomes included health related quality of life and biochemical laboratory data. All articles and outcomes were independently screened, extracted, and assessed for risk of bias and GRADE certainty of evidence at six and 12 month follow-up. Risk estimates and 95% confidence intervals were calculated using random effects meta-analysis. Outcomes were assessed according to a priori determined minimal important differences to determine clinical importance, and heterogeneity was investigated on the basis of risk of bias and seven a priori subgroups. Any subgroup effects with a statistically significant test of interaction were subjected to a five point credibility checklist. RESULTS Searches identified 14 759 citations yielding 23 trials (1357 participants), and 40.6% of outcomes were judged to be at low risk of bias. At six months, compared with control diets, LCDs achieved higher rates of diabetes remission (defined as HbA1c <6.5%) (76/133 (57%) v 41/131 (31%); risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264, I2=58%). Conversely, smaller, non-significant effect sizes occurred when a remission definition of HbA1c <6.5% without medication was used. Subgroup assessments determined as meeting credibility criteria indicated that remission with LCDs markedly decreased in studies that included patients using insulin. At 12 months, data on remission were sparse, ranging from a small effect to a trivial increased risk of diabetes. Large clinically important improvements were seen in weight loss, triglycerides, and insulin sensitivity at six months, which diminished at 12 months. On the basis of subgroup assessments deemed credible, VLCDs were less effective than less restrictive LCDs for weight loss at six months. However, this effect was explained by diet adherence. That is, among highly adherent patients on VLCDs, a clinically important reduction in weight was seen compared with studies with less adherent patients on VLCDs. Participants experienced no significant difference in quality of life at six months but did experience clinically important, but not statistically significant, worsening of quality of life and low density lipoprotein cholesterol at 12 months. Otherwise, no significant or clinically important between group differences were found in terms of adverse events or blood lipids at six and 12 months. CONCLUSIONS On the basis of moderate to low certainty evidence, patients adhering to an LCD for six months may experience remission of diabetes without adverse consequences. Limitations include continued debate around what constitutes remission of diabetes, as well as the efficacy, safety, and dietary satisfaction of longer term LCDs. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42020161795.