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Effects of Intermittent Energy Restriction Compared with Those of Continuous Energy Restriction on Body Composition and Cardiometabolic Risk Markers - A Systematic Review and Meta-Analysis of Randomized Controlled Trials in Adults.
Schroor, MM, Joris, PJ, Plat, J, Mensink, RP
Advances in nutrition (Bethesda, Md.). 2024;15(1):100130
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Intermittent energy restriction (IER) diets, such as the 5:2 diet, time-restricted eating (TRE), and alternate-day fasting (ADF), are gaining popularity. According to previous research, IER protocols effectively manage obesity and may have many other health benefits, including improving metabolic health. This systematic review and meta-analysis of twenty-eight parallel-design randomised controlled trials looked at the benefits of IER protocols, such as ADF, TRE, and the 5:2 diet, and the effects of continuous energy restriction (CER) on anthropometric and cardiometabolic outcomes. The results of this systematic review and meta-analysis showed that both the IER and CER are equally beneficial. However, IER protocols showed greater but clinically insignificant improvements in fat-free mass and waist circumference in healthy adults. IER and CER protocols were not different in improving the lipid profile, glucose and insulin levels and blood pressure. Different IER diets showed different positive effects on metabolic parameters. Future robust studies are required to assess the effects of these energy-restriction diets on metabolic and anthropometric parameters because of the high variability in the included studies. However, healthcare professionals can use the results of this review to understand the potential clinical utility of various energy-restriction diets.
Abstract
The interest in intermittent energy restriction (IER) diets as a weight-loss approach is increasing. Different IER protocols exist, including time-restricted eating (TRE), alternate-day fasting (ADF), and the 5:2 diet. This meta-analysis compared the effects of these IER diets with continuous energy restriction (CER) on anthropometrics and cardiometabolic risk markers in healthy adults. Twenty-eight trials were identified that studied TRE (k = 7), ADF (k = 10), or the 5:2 diet (k = 11) for 2-52 wk. Energy intakes between intervention groups within a study were comparable (17 trials), lower in IER (5 trials), or not reported (6 trials). Weighted mean differences (WMDs) were calculated using fixed- or random-effects models. Changes in body weight [WMD: -0.42 kg; 95% confidence interval (CI): -0.96 to 0.13; P = 0.132] and fat mass (FM) (WMD: -0.31 kg; 95% CI: -0.98 to 0.36; P = 0.362) were comparable when results of the 3 IER diets were combined and compared with those of CER. All IER diets combined reduced fat-free mass (WMD: -0.20 kg; 95% CI: -0.39 to -0.01; P = 0.044) and waist circumference (WMD: -0.91 cm; 95% CI: -1.76 to -0.06; P = 0.036) more than CER. Effects on body mass index [BMI (kg/m2)], glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), serum lipid and lipoprotein concentrations, and blood pressure did not differ. Further, TRE reduced body weight, FM, and fat-free mass more than CER, whereas ADF improved HOMA-IR more. BMI was reduced less in the 5:2 diet compared with CER. In conclusion, the 3 IER diets combined did not lead to superior improvements in anthropometrics and cardiometabolic risk markers compared with CER diets. Slightly greater reductions were, however, observed in fat-free mass and waist circumference. To what extent differences in energy intakes between groups within studies may have influenced these outcomes should be addressed in future studies.
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Effects of Probiotics on Glycemic Control and Metabolic Parameters in Gestational Diabetes Mellitus: Systematic Review and Meta-Analysis.
Yefet, E, Bar, L, Izhaki, I, Iskander, R, Massalha, M, Younis, JS, Nachum, Z
Nutrients. 2023;15(7)
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The prevalence of gestational diabetes is increasing worldwide. Gestational diabetes mellitus (GDM) increases obesity and future development of type 2 diabetes in mother and child. Previous research has looked at the beneficial effects of probiotics in reducing metabolic diseases, however, these specific benefits on women with GDM are not fully understood yet. This systematic review and meta-analysis of fourteen randomised controlled trials assessed the beneficial effects of probiotics on glycemic control and metabolic parameters in women with GDM. This study separately assessed probiotic bacterial strains such as Lactobacillus acidophilus, Bifidobacterium bifidum, and Lactobacillus casei to understand their beneficial effects on metabolic parameters. This meta-analysis and systematic review suggest that probiotic supplementation could help improve glycemic control, insulin resistance and lipid levels in women diagnosed with GDM. All probiotic strains showed improvements in metabolic parameters when assessed separately. Further robust studies are required to assess the effect of probiotic supplementation on post- and pre-prandial glycemic control in women with GDM. Healthcare professionals can employ the results of this study to understand the therapeutic benefits of probiotics for improving GDM.
Abstract
OBJECTIVES To assess the effects of probiotic supplements on glycemic control and metabolic parameters in women with gestational diabetes mellitus (GDM) by performing a systematic review and meta-analysis of randomized controlled trials. The primary outcome was glycemic control, i.e., serum glucose and insulin levels. Secondary outcomes were maternal weight gain, neonatal birth weight, and lipid parameters. Weighted mean difference (WMD) was used. Cochrane's Q test of heterogeneity and I2 were used to assess heterogeneity. RESULTS Of the 843 papers retrieved, 14 (n = 854 women) met the inclusion criteria and were analyzed. When compared with placebo, women receiving probiotic supplements had significantly lower mean fasting serum glucose, fasting serum insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, total cholesterol, and VLDL levels. Decreased neonatal birth weight was witnessed in supplements containing Lactobacillus acidophilus. CONCLUSION Probiotic supplements may improve glycemic control and lipid profile and reduce neonatal birth weight in women with GDM.
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High-fiber diet ameliorates gut microbiota, serum metabolism and emotional mood in type 2 diabetes patients.
Chen, L, Liu, B, Ren, L, Du, H, Fei, C, Qian, C, Li, B, Zhang, R, Liu, H, Li, Z, et al
Frontiers in cellular and infection microbiology. 2023;13:1069954
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Accumulating studies have demonstrated that there are strong correlations between type 2 diabetes mellitus (T2DM) and gut microbiota. A nutritious diet composed of an adequate level of dietary fibres could provide enough carbohydrates for the gut microbiota to ferment, and the microbial metabolites could provide energy supply and regulate the immune function of the host. The aim of this study was to analyse the changes in gut microbiota, serum metabolism and emotional mood of patients with T2DM after consumption of a high-fibre diet. This study was a randomised, open-label, parallel-group clinical trial in T2DM patients with a 4-week treatment period. Seventeen patients clinically diagnosed with T2DM enrolled in the clinical trial and were randomly assigned into two groups: the control group (n = 8) or the intervention group (n = 9). Results showed that the high-fibre diet (compared to the control group): - improved glucose homeostasis and lipid metabolism of participants with T2DM; - decreased serum levels of inflammatory chemokines in participants with T2DM; - alleviated depression and anxiety symptoms, particularly by the uptake of more diverse carbohydrates in the diet in participants with T2DM; - enhanced the diversity of gut microbiota in the treatment group. Authors conclude that the dietary source of fibre demonstrated protective impacts on the gut ecosystem, and the alteration of the gut microbiota composition improved the glucose homeostasis in patients with T2DM.
Abstract
Previous studies have demonstrated that patients with type 2 diabetes mellitus (T2DM) often had the problems of fecal microbiota dysbiosis, and were usually accompanied with psychiatric comorbidities (such as depression and anxiety). Here, we conducted a randomized clinical study to analyze the changes in gut microbiota, serum metabolism and emotional mood of patients with T2DM after consumption of a high-fiber diet. The glucose homeostasis of participants with T2DM was improved by the high-fiber diet, and the serum metabolome, systemic inflammation and psychiatric comorbidities were also altered. The increased abundances of Lactobacillus, Bifidobacterium and Akkermansias revealed that the proportions of beneficial gut microbes were enriched by the high-fiber diet, while the abundances of Desulfovibrio, Klebsiella and other opportunistic pathogens were decreased. Therefore, the current study demonstrated that the intestinal microbiota alterations which were influenced by the high-fiber diet could improve the serum metabolism and emotional mood of patients with T2DM.
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Sleep-Opt-In: A Randomized Controlled Pilot Study to Improve Sleep and Glycemic Variability in Adults With Type 1 Diabetes.
Martyn-Nemeth, P, Duffecy, J, Quinn, L, Steffen, A, Baron, K, Chapagai, S, Burke, L, Reutrakul, S
The science of diabetes self-management and care. 2023;49(1):11-22
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Insufficient sleep (insufficient total sleep time) and irregular sleep timing (variability in the occurrence of sleep within a 24-hour period) are increasingly recognized as important contributors to glycaemic control and variability in type 1 diabetes (T1D). The aims of this study were to evaluate the feasibility and acceptability of a sleep intervention (Sleep-Opt-In) targeted for adults with type 1 diabetes with short or irregular sleep and to examine the effects of Sleep-Opt-In on sleep duration and regularity, glucose indices, and patient-reported outcomes. This study was a randomised controlled parallel trial design. Participants (n=14) were randomly assigned to either the Sleep-Opt-In intervention or a Healthy Living attention control group. Results showed that: - Sleep-Opt-In was feasible and acceptable to the target population. - participants with objectively confirmed short or irregular sleep, sleep irregularity improved by 25 minutes on average, whereas sleep duration improved only negligibly (8 minutes). - the control group experienced an increase in sleep duration but no change in sleep regularity. Authors conclude that Sleep-Opt-In is feasible, acceptable, and promising for further evaluation to improve sleep duration or regularity, glucose parameters and important patient reported outcomes of diabetes distress, daytime sleepiness, fatigue and depressive mood in the T1D population.
Abstract
PURPOSE The purpose of this study was to evaluate the feasibility and acceptability of a technology-assisted behavioral sleep intervention (Sleep-Opt-In) and to examine the effects of Sleep-Opt-In on sleep duration and regularity, glucose indices, and patient-reported outcomes. Short sleep duration and irregular sleep schedules are associated with reduced glycemic control and greater glycemic variability. METHODS A randomized controlled parallel-arm pilot study was employed. Adults with type 1 diabetes (n = 14) were recruited from the Midwest and randomized 3:2 to the sleep-optimization (Sleep-Opt-In) or Healthy Living attention control group. Sleep-Opt-In was an 8-week, remotely delivered intervention consisting of digital lessons, sleep tracker, and weekly coaching phone calls by a trained sleep coach. Assessments of sleep (actigraphy), glucose (A1C, continuous glucose monitoring), and patient-reported outcomes (questionnaires for daytime sleepiness, fatigue, diabetes distress, and depressive mood) were completed at baseline and at completion of the intervention. RESULTS Sleep-Opt-In was feasible and acceptable. Those in Sleep-Opt-In with objectively confirmed short or irregular sleep demonstrated an improvement in sleep regularity (25 minutes), reduced glycemic variability (3.2%), and improved time in range (6.9%) compared to the Healthy Living attention control group. Patient-reported outcomes improved only for the Sleep-Opt-In group. Fatigue and depressive mood improved compared to the control. CONCLUSIONS Sleep-Opt-In is feasible, acceptable, and promising for further evaluation as a means to improve sleep duration or regularity in the population of people with type 1 diabetes.
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Effects of galactooligosaccharides on maternal gut microbiota, glucose metabolism, lipid metabolism and inflammation in pregnancy: A randomized controlled pilot study.
Wan, J, An, L, Ren, Z, Wang, S, Yang, H, Ma, J
Frontiers in endocrinology. 2023;14:1034266
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During pregnancy, a disordered gut microbiome and abnormal glucose metabolism may be possible mechanisms for pregnancy complications such as gestational diabetes mellitus (GDM). Different from probiotics, galactooligosaccharides (GOS) is a prebiotic that is not digested and absorbed by the host, but can selectively promote the metabolism and proliferation of beneficial bacteria in the body, particularly Lactobacillus and Bifidobacterium. The aim of this study was to evaluate the feasibility, acceptability, and safety of prebiotic intervention in healthy pregnant women, and conduct a preliminary exploration of the possible benefits for pregnant women. This study was a prospective double-blinded randomised clinical trial involving pregnant women. Participants were randomly assigned to the control group and the intervention group at a 1:1 ratio. Results showed that GOS intervention had no significant effect on reducing the incidence of GDM and improving glucose and lipid metabolism. Furthermore, there was no significant difference in glucose and lipid metabolism levels between GOS group and placebo group. Authors conclude that GOS can be considered as a dietary supplement during pregnancy. However, further clinical studies are needed to strengthen the findings of this study.
Abstract
BACKGROUND Gut microbiota of pregnant women change with the gestational week. On the one hand, they participate in the metabolic adaptation of pregnant women. On the other hand, the abnormal composition of gut microbiota of pregnant women is more likely to suffer from gestational diabetes mellitus (GDM). Therefore, gut microbiota targeted treatment through dietary supplements is particularly important for prevention or treatment. Prebiotic supplements containing galactooligosaccharides (GOS) may be an intervention method, but the effect is still unclear. OBJECTIVE This study aims to evaluate the feasibility and acceptability of prebiotic intervention in healthy pregnant women during pregnancy, and to explore the possible effects of intervention on pregnant women and the influence on gut microbiota as preliminaries. METHODS After recruitment in first trimester, 52 pregnant women were randomly assigned to receive GOS intervention or placebo containing fructooligosaccharides. 16S rRNA sequencing technology was used to detect the composition, diversity and differential flora of gut microbiota. Lipid metabolism, glucose metabolism and inflammatory factors during pregnancy were also analyzed. RESULTS The adverse symptoms of GOS intervention are mild and relatively safe. For pregnant women, there was no significant difference in the GDM incidence rates and gestational weight gain (GWG) in the GOS group compared with placebo (P > 0.05). Compared with the placebo group, the levels of FPG, TG, TC, HDL-C LDL-C, and IL-6 had no significant difference in GOS group (P > 0.05). For newborns, there was no significant difference between GOS group and placebo group in the following variables including gestational week, birth weight, birth length, head circumference, chest circumference, sex, and delivery mode (P > 0.05). And compared with the placebo group, the GOS group had a higher abundance of Paraprevotella and Dorea, but lower abundance of LachnospiraceaeUCG_001. CONCLUSIONS GOS prebiotics appear to be safe and acceptable for the enrolled pregnancies. Although GOS intervention did not show the robust benefits on glucose and lipid metabolism. However, the intervention had a certain impact on the compostion of gut microbiota. GOS can be considered as a dietary supplement during pregnancy, and further clinical studies are needed to explore this in the future.
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Impact of dietary interventions on pre-diabetic oral and gut microbiome, metabolites and cytokines.
Shoer, S, Shilo, S, Godneva, A, Ben-Yacov, O, Rein, M, Wolf, BC, Lotan-Pompan, M, Bar, N, Weiss, EI, Houri-Haddad, Y, et al
Nature communications. 2023;14(1):5384
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Pre-diabetes, a condition characterized by elevated blood glucose levels but below diabetes thresholds, is a significant risk factor for the development of type 2 diabetes, as well as other comorbidities including cardiovascular and kidney diseases. Diet plays a critical role in the development of hyperglycaemia and the onset of pre-diabetes. The aim of this study was to assess the impact of a personalized postprandial glucose-targeting diet (PPT), as well as the standard of care Mediterranean diet (MED), on the oral and gut microbiome, metabolites and cytokines in 200 pre-diabetic individuals. This study was a biphasic, randomised, controlled, single-blind dietary intervention. Phase one included a six-month intervention that compared two diets targeting glycaemic control, while phase two included a six-month follow-up period. Participants (n = 225) were randomly assigned in a 1:1 ratio to a PPT (n = 113) or a MED (n = 112). Results showed that participants assigned to the PPT diet had significant changes in 19 gut microbial species, 14 gut and one oral microbial pathway, 86 serum metabolites and four cytokines. Participants assigned to the MED diet showed significant changes in five gut and one oral microbial species, 18 gut microbial pathways, 27 serum metabolites and four cytokines. Authors conclude that dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host. Thus, diets such as the PPT used in this study, which takes into account microbiome features, could be designed to affect the microbiome and inflict desired metabolic outcomes.
Abstract
Diabetes and associated comorbidities are a global health threat on the rise. We conducted a six-month dietary intervention in pre-diabetic individuals (NCT03222791), to mitigate the hyperglycemia and enhance metabolic health. The current work explores early diabetes markers in the 200 individuals who completed the trial. We find 166 of 2,803 measured features, including oral and gut microbial species and pathways, serum metabolites and cytokines, show significant change in response to a personalized postprandial glucose-targeting diet or the standard of care Mediterranean diet. These changes include established markers of hyperglycemia as well as novel features that can now be investigated as potential therapeutic targets. Our results indicate the microbiome mediates the effect of diet on glycemic, metabolic and immune measurements, with gut microbiome compositional change explaining 12.25% of serum metabolites variance. Although the gut microbiome displays greater compositional changes compared to the oral microbiome, the oral microbiome demonstrates more changes at the genetic level, with trends dependent on environmental richness and species prevalence in the population. In conclusion, our study shows dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host, and that these factors are well associated with each other, and can be harnessed for new therapeutic modalities.
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Differential Responders to a Mixed Meal Tolerance Test Associated with Type 2 Diabetes Risk Factors and Gut Microbiota-Data from the MEDGI-Carb Randomized Controlled Trial.
Skantze, V, Hjorth, T, Wallman, M, Brunius, C, Dicksved, J, Pelve, EA, Esberg, A, Vitale, M, Giacco, R, Costabile, G, et al
Nutrients. 2023;15(20)
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Type 2 diabetes (T2D) is a growing worldwide health problem. Increased blood sugars and a corresponding increase in the production of the hormone insulin, which functions to lower blood sugar are risk factors for T2D development. However, it has been shown that everyone has an individual response to the food and the production of differing levels of blood sugar and insulin when eating the same meals has been shown. This secondary analysis of a 12-week randomised control trial of 155 individuals aimed to determine relationships between gut microbiota composition and the glucose response to high and low glycaemic index Mediterranean diets. The results identified two distinct types of response amongst the participants. Cluster A individuals had a lower but more rapid glucose response following food and were deemed to have a better glucose control than cluster B individuals. The clusters also differed in the gut microbiota composition. Cluster A had a higher proportion of Clostridium sensu stricto 1 and a lower proportion of Blautia, than cluster B. It was concluded that the glucose response to a standardised meal can differ between individuals and are associated with differing gut microbiota and risk for T2D. This study could be used by healthcare professionals to understand that diet recommendations are not one size fits all and that the recommendation of certain diets may have differing success. Understanding and differentiating individuals and tailor making recommendations may be of benefit, however further understanding is required on different glucose responses following a meal.
Abstract
The global prevalence of type 2 diabetes mellitus (T2DM) has surged in recent decades, and the identification of differential glycemic responders can aid tailored treatment for the prevention of prediabetes and T2DM. A mixed meal tolerance test (MMTT) based on regular foods offers the potential to uncover differential responders in dynamical postprandial events. We aimed to fit a simple mathematical model on dynamic postprandial glucose data from repeated MMTTs among participants with elevated T2DM risk to identify response clusters and investigate their association with T2DM risk factors and gut microbiota. Data were used from a 12-week multi-center dietary intervention trial involving high-risk T2DM adults, comparing high- versus low-glycemic index foods within a Mediterranean diet context (MEDGICarb). Model-based analysis of MMTTs from 155 participants (81 females and 74 males) revealed two distinct plasma glucose response clusters that were associated with baseline gut microbiota. Cluster A, inversely associated with HbA1c and waist circumference and directly with insulin sensitivity, exhibited a contrasting profile to cluster B. Findings imply that a standardized breakfast MMTT using regular foods could effectively distinguish non-diabetic individuals at varying risk levels for T2DM using a simple mechanistic model.
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Transform-Us! cluster RCT: 18-month and 30-month effects on children's physical activity, sedentary time and cardiometabolic risk markers.
Salmon, J, Arundell, L, Cerin, E, Ridgers, ND, Hesketh, KD, Daly, RM, Dunstan, D, Brown, H, Della Gatta, J, Della Gatta, P, et al
British journal of sports medicine. 2023;57(5):311-319
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Regular physical activity is beneficial to children’s physical, social and mental health. However, most children fail to meet the recommended 60+ min of moderate-intensity to vigorous-intensity physical activity every day. The Transform-Us! school-based and home-based intervention was developed to determine the impact of strategies to promote children’s moderate-to-vigorous physical activity versus reduce sedentary behaviour or a combination of these strategies, on behavioural and health outcomes. The main aim of this study was to determine the efficacy of the independent and combined intervention approaches to promoting physical activity and reducing sedentary behaviour on children’s moderate-to-vigorous physical activity and sedentary time after 18 and 30 months compared with usual practice. This study is a 30-month 2×2 factorial design cluster randomised controlled trial delivered in 20 primary schools with additional home intervention components. After recruitment, schools were then randomly allocated to one of four groups. Results show that Transform-Us! had stronger effects on children’s sedentary behaviour than physical activity in both the physical activity (PA) and sedentary behaviour (SB) interventions, and there were beneficial effects on children’s adiposity for both intervention approaches. However, no clear conclusions could be drawn regarding which intervention (PA or SB) had the strongest or more consistent effects on children’s health outcomes. Authors conclude that, based on their findings, government education departments and schools should consider adopting and implementing whole-of-school programmes to promote children’s physical activity and reduce sitting through active pedagogy and supportive social and physical environments at school and home to benefit children’s sedentary time and some markers of cardiometabolic health.
Abstract
OBJECTIVE To test the efficacy of the Transform-Us! school- and home-based intervention on children's physical activity (PA), sedentary behaviour (SB) and cardiometabolic risk factor profiles. METHODS A 30-month 2×2 factorial design cluster randomised controlled trial delivered in 20 primary schools (148 Year 3 classes) in Melbourne, Australia (2010-2012), that used pedagogical and environmental strategies to reduce and break up SB, promote PA or a combined approach, compared with usual practice. Primary outcomes (accelerometry data; n=348) were assessed at baseline, 18 and 30 months. Secondary outcomes included body mass index (BMI) and waist circumference (WC) (n=564), blood pressure (BP) (n=537) and biomarkers (minimum n=206). Generalised linear mixed models estimated the interactive effects of the PA and SB interventions on the outcomes. If there was no interaction, the main effects were assessed. RESULTS At 18 months, there were intervention effects on children's weekday SB (-27 min, 95% CI: -47.3 to -5.3) for the PA intervention, and on children's average day PA (5.5 min, 95% CI: 0.1 to 10.8) for the SB intervention. At 30 months, there was an intervention effect for children's average day SB (-33.3 min, 95% CI: -50.6 and -16.0) for the SB intervention. Children's BMI (PA and SB groups) and systolic BP (combined group) were lower, and diastolic BP (PA group) was higher. There were positive effects on WC at both time points (SB intervention) and mixed effects on blood parameters. CONCLUSIONS The Transform-Us! PA and SB interventions show promise as a pragmatic approach for reducing children's SB and adiposity indicators; but achieving substantial increases in PA remains challenging. TRIAL REGISTRATION ISRCTN83725066; ACTRN12609000715279.
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Nuts and seeds consumption and risk of cardiovascular disease, type 2 diabetes and their risk factors: a systematic review and meta-analysis.
Arnesen, EK, Thorisdottir, B, Bärebring, L, Söderlund, F, Nwaru, BI, Spielau, U, Dierkes, J, Ramel, A, Lamberg-Allardt, C, Åkesson, A
Food & nutrition research. 2023;67
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Nuts and seeds consumption is associated with a reduced risk of coronary heart disease (CHD) and cardiovascular disease (CVD). Nuts and seeds contain beneficial components to reduce the risk of CVD and CHD; hence dietary addition may benefit heart health. This systematic review and meta-analysis included sixty studies to analyse the effects of the consumption of nuts and seeds on the incidence of mortality from type 2 diabetes (T2D) and CVD and intermediate cardiometabolic risk factors. High nuts and seed consumption showed a 19% reduction in CVD risk and a 23% reduction in CVD mortality. In addition, high consumption lowered the risk of CHD by 25%. Increased nut consumption up to 30 g/day showed a dose-dependent relationship with reduced risk of CVD. Healthcare professionals can use the results of this study to understand the association between nuts and seeds consumption and CHD, CVD and blood lipid levels. However, further robust studies are required to evaluate the effect of specific nuts and seeds on CHD and CVD risk reduction.
Abstract
OBJECTIVES We aimed to systematically review studies and evaluate the strength of the evidence on nuts/seeds consumption and cardiometabolic diseases and their risk factors among adults. METHODS A protocol was pre-registered in PROSPERO (CRD42021270554). We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to September 20, 2021 for prospective cohort studies and ≥12-week randomized controlled trials (RCTs). Main outcomes were cardiovascular disease (CVD), coronary heart disease (CHD), stroke and type 2 diabetes (T2D), secondary total-/low density lipoprotein (LDL)-cholesterol, blood pressure and glycaemic markers. Data extraction and risk of bias (RoB) assessments (using RoB 2.0 and RoB-NObS) were performed in duplicate. Effect sizes were pooled using random-effects meta-analyses and expressed as relative risk (RR) or weighted mean differences with 95% confidence intervals (CI); heterogeneity quantified as I 2. One-stage dose-response analyses assessed the linear and non-linear associations with CVD, CHD, stroke and T2D. The strength of evidence was classified per the World Cancer Research Fund criteria. RESULTS After screening 23,244 references, we included 42 papers from cohort studies (28 unique cohorts, 1,890,573 participants) and 18 RCTs (2,266 participants). In the cohorts, mainly populations with low consumption, high versus low total nuts/seeds consumption was inversely associated with total CVD (RR 0.81; 95% CI 0.75, 0.86; I 2 = 67%), CVD mortality (0.77; 0.72, 0.82; I 2 = 59.3%), CHD (0.82; 0.76, 0.89; I 2 = 64%), CHD mortality (0.75; 0.65, 0.87; I 2 = 66.9%) and non-fatal CHD (0.85; 0.75, 0.96; I 2 = 62.2%). According to the non-linear dose-response analyses, consumption of 30 g/day of total nuts/seeds was associated with RRs of similar magnitude. For stroke and T2D the summary RR for high versus low intake was 0.91 (95% CI 0.85, 0.97; I 2 = 24.8%) and 0.95 (0.75, 1.21; I 2 = 82.2%). Intake of nuts (median ~50 g/day) lowered total (-0.15 mmol/L; -0.22, -0.08; I 2 = 31.2%) and LDL-cholesterol (-0.13 mmol/L; -0.21, -0.05; I 2 = 68.6%), but not blood pressure. Findings on fasting glucose, HbA1c and insulin resistance were conflicting. The results were robust to sensitivity and subgroup analyses. We rated the associations between nuts/seeds and both CVD and CHD as probable. There was limited but suggestive evidence for no association with stroke. No conclusion could be made for T2D. CONCLUSION There is a probable relationship between consumption of nuts/seeds and lower risk of CVD, mostly driven by CHD, possibly in part through effects on blood lipids. More research on stroke and T2D may affect the conclusions. The evidence of specific nuts should be further investigated.
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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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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.