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Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.
Xia, J, Yu, J, Xu, H, Zhou, Y, Li, H, Yin, S, Xu, D, Wang, Y, Xia, H, Liao, W, et al
Pharmacological research. 2023;188:106647
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Type 2 diabetes mellitus (T2DM), characterised by sustained hyperglycaemia and insulin resistance, remains a severe driver of chronic metabolic diseases such as cardiovascular diseases. The aim of this study was to investigate and compare the efficacy of vitamin and mineral supplements in the management of glycaemic control and lipid metabolism for type 2 diabetic patients to inform clinical practice. This study is a systematic review and meta-analysis of one hundred and seventy articles with a total of 4223 adults with T2DM. Participants were randomised to either the placebo/no treatment group (n= 6345) or to the treatment group (n= 7878). Results show that: - chromium was the most effective micronutrient for decreasing fasting blood glucose and insulin resistance. - vitamin K was the top-ranked micronutrient in reducing haemoglobin A1C and fasting insulin levels. - vanadium was the top-ranked micronutrient in total cholesterol reductions. - niacin was ranked as the most effective in triglycerides reductions and increasing high-density lipoprotein cholesterol levels. - vitamin E was the top-ranked micronutrient in low-density lipoprotein cholesterol reductions. Authors conclude that micronutrient supplements especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more effective in the management of T2DM compared with other micronutrients.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Clinicians could consider the adjunctive effect of micronutrients supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements in a nutrition protocol to manage T2DM and slow or prevent its complications.
- The study authors state that the vitamin and mineral supplements under review had a statistically significant improvement, however they did not reach the study threshold for clinical significance. Therefore they advise caution in utilising micronutrient supplements in the management of glucose and lipid metabolism for T2DM.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Objectives
The aim of this systematic review was to evaluate the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM).
Methodology
This systematic review is registered with PROSPERO and adhered to PRISMA-2020 guidelines for network meta-analysis
The Cochrane Collaboration’s risk-of-bias tool was used to assess eligible randomised trials
8 prespecified markers identified and assessed in this study : 1) HbA1c (%), 2) fasting blood glucose (mmol/L), 3) total cholesterol (mmol/L), 4) triglycerides (mmol/L), 5) fasting insulin (μIU/mL), 6) HOMA-IR, 7) LDL-c (mmol/L), and 8) HDL-c (mmol/L).
Results
- 170 RCT trials of 14223 participants with T2DM treated with vitamin supplements, mineral supplements, or placebo/no treatment were included
- Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively)
- Vitamin K supplements ranked best in reducing glycated haemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence
- Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%)
- Niacin supplements ranked best in triglyceride reductions and increasing high-density lipo-protein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively)
- Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%).
Conclusion
- Micronutrient supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be efficacious in managing T2DM
- It should be noted that the evidence certainty for all was low.
Clinical practice applications:
- Chromium plays an important role in carbohydrate and lipid metabolism and was the most effective micronutrient for decreasing fasting blood glucose, HbA1c, fasting insulin, and HOMA-IR reductions. More pronounced effects were seen for chromium than vitamin E, vitamin C, niacin, selenium, and magnesium supplements
- Vitamin K was the top-ranked micronutrient in reducing HbA1c and fasting insulin levels. The mechanism through which Vitamin K affects glucose metabolism is proposed as activation of the AMP-activated protein kinase/sirtuin 1, that in turn increases phosphocreatine 3-kinase and glucose transporter 2 to decrease insulin resistance and fasting glucose.
- Vanadium was the top-ranked micronutrient in total cholesterol (TC) reductions, where supplementation dosage should be carefully considered, as vanadium compounds can be moderately or highly toxic. Vanadium supplementation is only recommended in cases of vanadium deficiency or diabetes, hyperlipidemia, and hypertension, where the intake of vanadium from food should be enhanced in preference to supplementation
- Niacin was ranked as the most effective in triglyceride (TG) reductions and increasing HDL cholesterol levels. The dose of niacin could not be determined
- Vitamin E was the top-ranked micronutrient in low-density lipo- protein (LDL) cholesterol reductions.
Considerations for future research:
- Considering the clinical importance of these findings, new research is needed to get better insight into the efficacy of micronutrient supplements in managing T2DM
- Selenium homeostasis, selenoprotein, insulin signaling/secretion, and carbohydrate/lipid metabolism are linked in multiple and complex ways but the authors could not explain why chromium supplementation would lower blood glucose more effectively than selenium supplementation, and suggest more research is needed to clarify this
- While vitamin K status could be an emerging treatment target in T2DM prevention and management, it remains to be determined whether vitamin K supplementation has an advantage over other nutrients in terms of hypoglycemic effect, and further research is necessary
- The beneficial effect of vitamin E and niacin supplements regarding lipid metabolism warrant investigation through more rigorous comparative studies.
Abstract
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
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Evidence of lifestyle interventions in a pregnant population with chronic hypertension and/or pre-existing diabetes: A systematic review and narrative synthesis.
Goddard, L, Patel, R, Astbury, NM, Tucker, K, McManus, RJ
Pregnancy hypertension. 2023;31:60-72
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Chronic hypertension complicates ≤5 % of pregnancies, and those entering pregnancy with a pre-existing diagnosis of diabetes has a global prevalence of between 0.5 % and 2.6 %. The aim of this study was to collate the evidence around lifestyle interventions during pregnancy for women with chronic hypertension and/or pre-existing diabetes (type 1 and type 2). This study is a systematic review and meta-analysis of nine randomised controlled trials. Results show lack of clarity and data on the effect of lifestyle interventions in pregnant women with chronic hypertension and/or pre-existing diabetes, thereby exposing key gaps in the literature. Authors conclude that there is a shortage of primary interventional studies examining the effect of lifestyle interventions in high-risk pregnant populations who enter pregnancy with chronic conditions.
Abstract
BACKGROUND Pregnant people with chronic hypertension, pre-existing diabetes or both are at high risk of developing cardiovascular disease. Lifestyle interventions play an important role in disease management in non-pregnant populations. AIM: To review the existing evidence of randomised controlled trials (RCTs) that examine lifestyle interventions in pregnant people with chronic hypertension and/or pre-existing diabetes. METHODS A systematic review and narrative synthesis was conducted. Five electronic databases were searched from inception to April 2021 for RCTs evaluating antenatal lifestyle interventions in people with chronic hypertension and/or pre-existing diabetes with outcomes to include weight or blood pressure change. RESULTS Nine randomised controlled trials including 7438 pregnant women were eligible. Eight studies were mixed pregnant populations that included women with chronic hypertension and/or pre-existing diabetes. One study included only pregnant women with pre-existing diabetes. Intervention characteristics and procedures varied and targeted diet, physical activity and/or gestational weight. All studies reported weight and one study reported blood pressure change. Outcome data were frequently unavailable for the subset of women of interest, including subgroup data on important pregnancy and birth complications. Eligibility criteria were often ambiguous and baseline data on chronic hypertension was often omitted. CONCLUSION A lack of primary interventional trials examining the effect of lifestyle interventions on weight and blood pressure outcomes in pregnant populations with chronic hypertension and/or pre-existing diabetes was evident. Lifestyle modification has the potential to alter disease progression. Future trials should address the ambiguity and frequent exclusion of these important populations.
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Effect of Peanut Consumption on Cardiovascular Risk Factors: A Randomized Clinical Trial and Meta-Analysis.
Parilli-Moser, I, Hurtado-Barroso, S, Guasch-Ferré, M, Lamuela-Raventós, RM
Frontiers in nutrition. 2022;9:853378
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Peanuts contain bioactive substances that are beneficial for cardiovascular health. This three-arm, parallel-group randomised controlled trial (ARISTOTLE) and meta-analysis evaluated the beneficial effects of high-oleic peanuts and peanut butter in improving cardiometabolic health. Participants in the randomised controlled trial consumed 25 g of skin-roasted peanuts or 32 g of peanut butter, or a control butter made with peanut oil without fibre and polyphenols for six months. The skin-roasted peanuts group showed a reduction in total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios. The meta-analysis was highly heterogeneous in participant ethnicity, health status, peanut intervention dosage and duration. The dosage of peanuts, peanut butter and high oleic peanuts used was between 25 and 200 g/day. The participants were healthy, with metabolic syndrome (MeS), or at risk of MeS. There was a significant increase in body weight among those with or at risk of MeS. In addition, healthy participants showed reduced triglycerides, total cholesterol, and LDL-cholesterol/HDL-cholesterol ratios. Healthcare professionals can use the results of this research to understand the beneficial impact of peanut consumption on the lipid profile. However, further robust studies are required due to the high heterogeneity of the included studies in the meta-analysis.
Abstract
UNLABELLED Although numerous studies have reported the protective effect of nut consumption on cardiovascular risk, evidence for the role of peanuts in maintaining cardiometabolic health is inconclusive. Presented here are the results from the ARISTOTLE study, a parallel randomized controlled trial evaluating the impact of regular peanut intake on anthropometric, biochemical, and clinical measurements. The 63 healthy subjects that completed the study consumed their habitual diet plus either: a) 25 g/day of skin roasted peanuts (SRP, n = 21), b) two tablespoons (32 g)/day of peanut butter (PB, n = 23) or c) two tablespoons (32 g)/day of a control butter based on peanut oil (CB, n = 19) for 6 months. In addition, a meta-analysis of clinical trials, including data from the ARISTOTLE study, was carried out to update the evidence for the effects of consuming peanuts, including high-oleic peanuts, and peanut butter on healthy subjects and those at high cardiometabolic risk. After a systematic search on PubMed, Web of Science, Cochrane Library and Scopus databases up to July 2021, 11 studies were found to meet the eligibility criteria. In the ARISTOTLE study, lower total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios were found in the SRP group compared to the CB group (p = 0.019 and p = 0.008). The meta-analysis of clinical trials revealed that peanut consumption is associated with a decrease in triglycerides (MD: -0.13; 95% CI, -0.20 to -0.07; p < 0.0001) and that healthy consumers had lower total cholesterol and LDL-cholesterol/HDL-cholesterol ratios compared to the control groups (MD: -0.40; 95% CI, -0.71 to -0.09; p = 0.01 and MD: -0.19; 95% CI, -0.36 to -0.01; p = 0.03, respectively). However, individuals at high cardiometabolic risk experienced an increase in body weight after the peanut interventions (MD: 0.97; 95% CI, 0.54 to 1.41; p < 0.0001), although not in body fat or body mass index. According to the dose-response analyses, body weight increased slightly with higher doses of peanuts. In conclusion, a regular consumption of peanuts seems to modulate lipid metabolism, reducing triglyceride blood levels. SYSTEMATIC REVIEW REGISTRATION https://osf.io/jx34y/, identifier: 10.17605/OSF.IO/MK35Y.
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Effects of camelina oil supplementation on lipid profile and glycemic control: a systematic review and dose‒response meta-analysis of randomized clinical trials.
Jalili, C, Talebi, S, Mehrabani, S, Bagheri, R, Wong, A, Amirian, P, Zarpoosh, M, Ghoreishy, SM, Kermani, MAH, Moradi, S
Lipids in health and disease. 2022;21(1):132
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Research indicates that alpha-linolenic acid (ALA) can reduce the risk of cardiovascular disease by improving blood lipids, blood pressure, and haemostatic factors, among others. Camelina oil, considered a good source of ALA compared to other edible oils, is one of the richest dietary sources of omega-3 fatty acids, with a polyunsaturated fatty acid content over 50%. The aim of this study was to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycaemic control in human studies. This study is a systematic review and meta-analysis of seven randomised controlled trials with a total of 428 individuals (202 participants in the COS group and 226 in the control group). Results did not show any affects of COS on lipid profile and glycaemic indices compared with placebo intake. However, subgroup analysis showed that COS for more than 8 weeks and at a dose lower than 30g/d could decrease total cholesterol. Authors conclude that COS may be a beneficial nonpharmacological strategy for the improvement of this lipid marker. However, further studies are required to confirm the findings of this study.
Abstract
BACKGROUND This systematic review and dose-response meta-analysis of published randomized controlled trials (RCTs) was conducted to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycemic indices. METHODS Relevant RCTs were selected by searching the ISI Web of Science, PubMed, and Scopus databases up to July 1, 2022. RTCs with an intervention duration of less than 2 weeks, without a placebo group, and those that used COS in combination with another supplement were excluded. Weighted mean differences and 95% confidence intervals were pooled by applying a random-effects model, while validated methods examined sensitivity analyses, heterogeneity, and publication bias. RESULTS Seven eligible RCTs, including 428 individuals, were selected. The pooled analysis revealed that COS significantly improved total cholesterol in studies lasting more than 8 weeks and utilizing dosages lower than 30 g/d compared to the placebo group. The results of fractional polynomial modeling indicated that there were nonlinear dose-response relations between the dose of COS and absolute mean differences in low-density cholesterol, high-density cholesterol, and total cholesterol, but not triglycerides. It appears that the greatest effect of COS oil occurs at the dosage of 20 g/day. CONCLUSION The present meta-analysis indicates that COS may reduce cardiovascular disease risk by improving lipid profile markers. Based on the results of this study, COS at dosages lower than 30 g/d may be a beneficial nonpharmacological strategy for lipid control. Further RCTs with longer COS durations are warranted to expand on these results.
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Effects of lifestyle interventions on cardiovascular risk factors in South Asians: a systematic review and meta-analysis.
Limbachia, J, Ajmeri, M, Keating, BJ, de Souza, RJ, Anand, SS
BMJ open. 2022;12(12):e059666
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The prevalence of cardiovascular disease (CVD) and associated mortality risk is high in the South Asian population in western countries. Regular physical activity and a healthy diet may modify the risk factors of CVD, such as abdominal fat, high cholesterol, and blood sugar irregularities. This systematic review and meta-analysis included thirty-five randomised controlled trials to evaluate the effectiveness of diet, physical activity interventions or a combination of diet and physical activity interventions on CVD risk factors and compared it against usual care. Combining diet and physical activity interventions reduced CVD risk factors such as systolic and diastolic blood pressure, BMI, weight, waist circumference and fasting plasma glucose (FPG). Dietary interventions reduced diastolic blood pressure, triglycerides, low-density lipoprotein cholesterol, BMI, weight and FPG. Physical activity modifications improved diastolic and systolic blood pressure and high-density lipoprotein cholesterol. Healthcare professionals can use the study results to understand how tailored diet and physical activity modifications improve the CVD risk factors in South Asians. However, further robust studies are required as most of these evidences were of moderate quality and lacked clinical significance.
Abstract
BACKGROUND The cardiovascular disease (CVD) burden among South Asians is high. Lifestyle interventions have been effective in the primary prevention of CVD, but this has not been replicated, through a synthesis of randomised trials, in South Asians. METHODS Four electronic databases (MEDLINE, Embase, CENTRAL and CINAHL), two clinical trial registries and references of included articles were searched through June 2022 (featuring ≥90% South Asian participants). Random-effects pairwise meta-analyses were performed, and heterogeneity was quantified with the I2 statistic. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework was used to report on the quality of evidence (International Prospective Register of Systematic Reviews registration (PROSPERO). RESULTS Thirty-five studies were included. Twelve tested diet and physical activity interventions; 18 tested diet alone; and 5 tested physical activity alone. All reported effects of the intervention(s) on at least one established risk factor for CVD, including blood pressure (systolic blood pressure (SBP), diastolic blood pressure (DBP) and blood lipids (high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc) or triglycerides). No trials reported clinical CVD. There is moderate-quality evidence that diet and physical activity interventions improve SBP (mean difference (MD) -2.72 mm Hg, 95% CI -4.11 to -1.33) and DBP (MD -1.53 mm Hg, 95% CI -2.57 to -0.48); high-quality to moderate-quality evidence that diet-only interventions improve DBP (MD -2.05 mm Hg, 95% CI -2.93 to -1.16) and blood lipids (triglycerides (MD -0.10 mmol/L, 95% CI -0.14 to -0.06) and LDLc (MD -0.19 mmol/L, 95% CI -0.32 to -0.06)); and moderate-quality evidence that physical activity-only interventions improve SBP (MD -9.7 mm Hg, 95% CI -11.05 to -8.35), DBP (MD -7.29 mm Hg, 95% CI -8.42 to -6.16) and HDLc (MD 0.08 mmol/L, 95% CI 0.04 to 0.11) compared with usual care. CONCLUSIONS Lifestyle interventions improve blood pressure and blood lipid profiles in adult South Asians at risk of CVD. Tailored interventions should be used to modify cardiovascular risk factors in this at-risk group. PROSPERO REGISTRATION NUMBER CRD42018090419.
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Effects of the Treatment with Flavonoids on Metabolic Syndrome Components in Humans: A Systematic Review Focusing on Mechanisms of Action.
Gouveia, HJCB, Urquiza-Martínez, MV, Manhães-de-Castro, R, Costa-de-Santana, BJR, Villarreal, JP, Mercado-Camargo, R, Torner, L, de Souza Aquino, J, Toscano, AE, Guzmán-Quevedo, O
International journal of molecular sciences. 2022;23(15)
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Metabolic syndrome is a condition characterised by at least three of the five risk factors, such as abdominal obesity, elevated fasting glucose, blood pressure and triglycerides and reduced high-density lipoprotein cholesterol (HDL-c). There is a strong link between metabolic syndrome and the development of cardiovascular disease and Type 2 diabetes. Research suggests that increasing consumption of flavonoid-rich foods can be beneficial in reducing cardiovascular morbidity and mortality. Flavonoids are bioactive compounds that possess antioxidative, anti-inflammatory, anti-cancerous, anti-mutagenic, and enzymatic properties. This systematic review of 29 randomised controlled trials evaluated the beneficial effects of long-term flavonoid supplementation in reducing the risk factors of metabolic syndrome. This review included a variety of flavonoid supplements, such as anthocyanin, hesperidin, quercetin, epigallocatechin gallate (egcg), genistein, theaflavin, catechin, and eriocitrin. Additionally, this research investigated the mechanisms behind the beneficial effects of flavonoid supplementation. Results showed that flavonoid supplementation for at least three weeks improved metabolic parameters and inflammatory markers, with hesperidin showing the greatest improvements in metabolic parameters. Healthcare professionals can use these findings to understand the potential benefits of long-term flavonoid supplementation in improving metabolic parameters. However, more robust studies are needed to determine the therapeutic dosages of different flavonoids.
Abstract
Diets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS). Polyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, tea, red wine, and cocoa. Studies have already demonstrated the benefits of flavonoids on the cardiovascular and nervous systems, as well as cancer cells. The present review summarizes the results of clinical studies that evaluated the effects of flavonoids on the components of the MetS and associated complications when offered as supplements over the long term. The results show that flavonoids can significantly modulate several metabolic parameters, such as lipid profile, blood pressure, and blood glucose. Only theaflavin and catechin were unable to affect metabolic parameters. Moreover, only body weight and body mass index were unaltered. Thus, the evidence presented in this systematic review offers bases in support of a flavonoid supplementation, held for at least 3 weeks, as a strategy to improve several metabolic parameters and, consequently, reduce the risk of diseases associated with MetS. This fact becomes stronger due to the rare side effects reported with flavonoids.
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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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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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Association of gestational diabetes mellitus with overall and type specific cardiovascular and cerebrovascular diseases: systematic review and meta-analysis.
Xie, W, Wang, Y, Xiao, S, Qiu, L, Yu, Y, Zhang, Z
BMJ (Clinical research ed.). 2022;378:e070244
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Gestational diabetes mellitus, defined as glucose intolerance with first onset during pregnancy, usually resolves after birth, however, a growing number of long-term observational studies suggest that the impact persists over time. The increased cardiovascular risk in women with gestational diabetes mellitus has been increasingly recognised. The aim of this study was to quantify the risks of overall and type specific cardiovascular and cerebrovascular diseases in women with gestational diabetes mellitus. This study is a systematic review and meta-analysis of fifteen studies. The study included almost nine million women. Results show that participants with a history of gestational diabetes mellitus were at significantly increased risks of cardiovascular and cerebrovascular diseases in general and at variable risks for most common types of cardiovascular and cerebrovascular diseases. Authors conclude that their findings highlight the need for early intervention in women at high risk of gestational diabetes mellitus, and for continuous monitoring of women with a history of gestational diabetes mellitus after pregnancy.
Abstract
OBJECTIVE To quantify the risk of overall and type specific cardiovascular and cerebrovascular diseases as well as venous thromboembolism in women with a history of gestational diabetes mellitus. DESIGN Systematic review and meta-analyses. DATA SOURCES PubMed, Embase, and the Cochrane Library from inception to 1 November 2021 and updated on 26 May 2022. REVIEW METHODS Observational studies reporting the association between gestational diabetes mellitus and incident cardiovascular and cerebrovascular diseases were eligible. Data, pooled by random effects models, are presented as risk ratios (95% confidence intervals). Certainty of evidence was appraised by the Grading of Recommendations, Assessment, Development, and Evaluations. RESULTS 15 studies rated as moderate or serious risk of bias were included. Of 513 324 women with gestational diabetes mellitus, 9507 had cardiovascular and cerebrovascular disease. Of more than eight million control women without gestational diabetes, 78 895 had cardiovascular and cerebrovascular disease. Compared with women without gestational diabetes mellitus, women with a history of gestational diabetes mellitus showed a 45% increased risk of overall cardiovascular and cerebrovascular diseases (risk ratio 1.45, 95% confidence interval 1.36 to 1.53), 72% for cardiovascular diseases (1.72, 1.40 to 2.11), and 40% for cerebrovascular diseases (1.40, 1.29 to 1.51). Women with gestational diabetes mellitus showed increased risks of incident coronary artery diseases (1.40, 1.18 to 1.65), myocardial infarction (1.74, 1.37 to 2.20), heart failure (1.62, 1.29 to 2.05), angina pectoris (2.27, 1.79 to 2.87), cardiovascular procedures (1.87, 1.34 to 2.62), stroke (1.45, 1.29 to 1.63), and ischaemic stroke (1.49, 1.29 to 1.71). The risk of venous thromboembolism was observed to increase by 28% in women with previous gestational diabetes mellitus (1.28, 1.13 to 1.46). Subgroup analyses of cardiovascular and cerebrovascular disease outcomes stratified by study characteristics and adjustments showed significant differences by region (P=0.078), study design (P=0.02), source of data (P=0.005), and study quality (P=0.04), adjustment for smoking (P=0.03), body mass index (P=0.01), and socioeconomic status (P=0.006), and comorbidities (P=0.05). The risk of cardiovascular and cerebrovascular diseases was, however, attenuated but remained significant when restricted to women who did not develop subsequent overt diabetes (all gestational diabetes mellitus: 1.45, 1.33 to 1.59, gestational diabetes mellitus without subsequent diabetes: 1.09, 1.06 to 1.13). Certainty of evidence was judged as low or very low quality. CONCLUSIONS Gestational diabetes mellitus is associated with increased risks of overall and type specific cardiovascular and cerebrovascular diseases that cannot be solely attributed to conventional cardiovascular risk factors or subsequent diabetes.
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Intermittent Fasting versus Continuous Calorie Restriction: Which Is Better for Weight Loss?
Zhang, Q, Zhang, C, Wang, H, Ma, Z, Liu, D, Guan, X, Liu, Y, Fu, Y, Cui, M, Dong, J
Nutrients. 2022;14(9)
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Obesity increases the risk of developing metabolic syndrome, diabetes, cardiovascular disease and associated comorbidities. Intermittent fasting (IF) and continuous calorie restriction (CCR) are fasting regimens known to reduce weight, which is at the heart of strategy in reducing obesity. IF and CCR restricts energy intake; however, CCR is harder to follow than IF. IF focuses more on time-restricted eating. This systematic review and meta-analysis examined the effectiveness of IF and CCR on body mass index (BMI), body weight, and metabolism in overweight and obese participants. This research showed that IF is significantly superior to CCR in weight loss in obese people. However, there was no difference in BMI between both regimens. There was a significant difference between IF and CCR for total cholesterol, triacylglycerol, and waist circumference. Further larger long-term robust studies are required to evaluate the effectiveness of different fasting regimens due to the high heterogeneity in this research. Healthcare professionals can use the results of this study to distinguish the weight loss effects between different fasting regimens.
Abstract
We conducted a systematic review and meta-analysis of randomized clinical trials and pilot trial studies to compare the effectiveness of intermittent fasting (IF) and continuous calorie restriction (CCR) in overweight and obese people. The parameters included body mass index (BMI), body weight, and other metabolism-related indicators. A systematic search in PubMed, Embase, Cochrane Library, and Web of Science was conducted up to January 2022. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to measure the effectiveness. Publication bias was assessed using Egger's test. The stability of the results was evaluated using sensitivity analyses. The significance of body weight change (SMD = -0.21, 95% CI (-0.40, -0.02) p = 0.028) was more significant after IF than CCR. There was no significant difference in BMI (SMD = 0.02, 95% CI (-0.16, 0.20) p = 0.848) between IF and CCR. These findings suggest that IF may be superior to CCR for weight loss in some respects.
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The Dose-Response Associations of Sugar-Sweetened Beverage Intake with the Risk of Stroke, Depression, Cancer, and Cause-Specific Mortality: A Systematic Review and Meta-Analysis of Prospective Studies.
Wang, Y, Zhao, R, Wang, B, Zhao, C, Zhu, B, Tian, X
Nutrients. 2022;14(4)
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The consumption of sugar-sweetened beverages is high in today's society, which may lead to weight gain, inflammation, and a number of obesity-associated diseases. The objective of this systematic review and meta-analysis was to investigate the associations and causal links between the consumption of sugar-sweetened beverages and cancer, stroke, depression, and cause-specific mortality. Consumption of sugar-sweetened beverages significantly increased the risk of cancer, strokes, depression, and cause-specific mortality when compared with the consumption of low or no-sugar-sweetened beverages. As little as a 250ml increment of sugar-sweetened beverages was associated with an increase in risk. Consumption of sugar-sweetened beverages increases the risk of ischemic stroke by 10%, CVD-caused mortality by 13%, and cancer-caused mortality by 6.0% compared to those who consume less or no sugar-sweetened beverages. These findings can be used by healthcare professionals to understand the clinical significance of intervention strategies that reduce the consumption of sugar-sweetened beverages. It is imperative to conduct additional robust studies as there is an insufficient amount of evidence at present to establish a causal connection between the consumption of sugary beverages and the risk of depression, stroke, cancer, and cause-specific mortality.
Abstract
The associations between sugar-sweetened beverage (SSB) consumption and the risk of stroke, depression, cancer, and cause-specific mortality have not been determined, and the quantitative aspects of this link remain unclear. This meta-analysis therefore conducted a systematic review and dose-response analysis to determine their causal links. The database searches were conducted in PubMed, Cochrane library, Embase, Web of Science up to 10 November 2021. The intervention effects were evaluated by relative risk (RR) with 95% confidences (CI). Thirty-two articles met the inclusion criteria. Higher levels of SSB consumption significantly increased the risk of stroke (RR 1.12, 95% CI 1.03-1.23), depression (1.25, 1.11-1.41), cancer (1.10, 1.03-1.17), and all-cause mortality (1.08, 1.05-1.11) compared with none or lower SSB intake. The associations were dose-dependent, with per 250 mL increment of SSB intake daily increasing the risk of stroke, depression, cancer, and all-cause mortality by RR 1.09 (1.03-1.15), 1.08 (1.06-1.10), 1.17 (1.04-1.32), and 1.07 (1.03-1.11), respectively. The link was curved for depression and cancer risk (pnon-linear < 0.05). Subgroup analysis suggested that higher SSB intake increased ischemic stroke by 10%, CVD-caused mortality by 13%, and cancer-caused mortality by 6.0% than none or lower SSB consumption. It is suggested that SSB accounts for a leading risk factor of stroke, depression, cancer, and mortality, and that the risk rises in parallel with the increment of SSB intake (and is affected by participant characteristics).