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Effects of Wholegrain Compared to Refined Grain Intake on Cardiometabolic Risk Markers, Gut Microbiota, and Gastrointestinal Symptoms in Children: A Randomized Crossover Trial.
Madsen, MTB, Landberg, R, Nielsen, DS, Zhang, Y, Anneberg, OMR, Lauritzen, L, Damsgaard, CT
The American journal of clinical nutrition. 2024;119(1):18-28
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High consumption of wholegrain foods has been linked to a lower risk of cardiovascular disease (CVD) and type 2 diabetes. Some trials have shown benefits to body weight, blood lipids and glucose homeostasis but most of these studies are with adults. Cardiometabolic disease begins in childhood therefore data is needed for this age group to back up dietary recommendations in order to prevent later development of cardiometabolic disease. The aim of this randomized crossover trial was to look at the effects of wholegrain oats and rye intake on serum low-density lipoprotein (LDL), cholesterol and plasma insulin, other cardiometabolic markers, body composition, the composition of the gut microbiome and gastrointestinal symptoms in children with high body mass index (BMI). 55 healthy Danish children (aged 8 – 13) took part. They ate wholegrain oats and rye (WG) or refined grain products (RG) ad libtum for 8 weeks in random order. Measurements were taken at 0, 8 and 16 weeks. Compared with RG, WG reduced LDL cholesterol as well as total:high-density lipoprotein cholesterol and triacylglycerol. WG also modulated the abundance of specific types of gut bacteria, increased plasma acetate, propionate, and butyrate and fecal butyrate and reduced fatigue with no other effects on gut symptoms. This study supports the recommendation to swap refined grain for wholegrain oats and rye in children. Further studies are needed.
Abstract
BACKGROUND Wholegrain intake is associated with lower risk of cardiometabolic diseases in adults, potentially via changes in the gut microbiota. Although cardiometabolic prevention should start early, we lack evidence on the effects in children. OBJECTIVES This study investigated the effects of wholegrain oats and rye intake on serum low-density lipoprotein (LDL) cholesterol and plasma insulin (coprimary outcomes), other cardiometabolic markers, body composition, gut microbiota composition and metabolites, and gastrointestinal symptoms in children with high body mass index (BMI). METHODS In a randomized crossover trial, 55 healthy Danish 8- to 13-y-olds received wholegrain oats and rye ("WG") or refined grain ("RG") products ad libitum for 8 wk in random order. At 0, 8, and 16 wk, we measured anthropometry, body composition by dual-energy absorptiometry, and blood pressure. Fasting blood and fecal samples were collected for analysis of blood lipids, glucose homeostasis markers, gut microbiota, and short-chain fatty acids. Gut symptoms and stool characteristics were determined by questionnaires. Diet was assessed by 4-d dietary records and compliance by plasma alkylresorcinols (ARs). RESULTS Fifty-two children (95%) with a BMI z-score of 1.5 ± 0.6 (mean ± standard deviation) completed the study. They consumed 108 ± 38 and 3 ± 2 g/d wholegrain in the WG and RG period, which was verified by a profound difference in ARs (P < 0.001). Compared with RG, WG reduced LDL cholesterol by 0.14 (95% confidence interval: -0.24, -0.04) mmol/L (P = 0.009) and reduced total:high-density lipoprotein cholesterol (P < 0.001) and triacylglycerol (P = 0.048) without altering body composition or other cardiometabolic markers. WG also modulated the abundance of specific bacterial taxa, increased plasma acetate, propionate, and butyrate and fecal butyrate and reduced fatigue with no other effects on gut symptoms. CONCLUSION High intake of wholegrain oats and rye reduced LDL cholesterol and triacylglycerol, modulated bacterial taxa, and increased beneficial metabolites in children. This supports recommendations of exchanging refined grain with wholegrain oats and rye among children. This trial was registered at clinicaltrials.gov as NCT04430465.
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Prebiotic diet changes neural correlates of food decision-making in overweight adults: a randomised controlled within-subject cross-over trial.
Medawar, E, Beyer, F, Thieleking, R, Haange, SB, Rolle-Kampczyk, U, Reinicke, M, Chakaroun, R, von Bergen, M, Stumvoll, M, Villringer, A, et al
Gut. 2024;73(2):298-310
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It is thought that there is a connection between the gut microbiota and the brain and that prebiotics which fuel these gut microbiota may be able to affect mood and decision making. This randomised control trial of 59 individuals with overweight aimed to determine if supplementation of prebiotic fibre in the form of inulin could affect the desire for food. The results showed that compared to placebo individuals given inulin had a lower desire towards high caloric foods in conjunction with a change in the composition of the gut microbiota, especially Bifidobacteriaceae. It was concluded that prebiotics may be able to alter food-related decision making and alter the composition of the gut microbiota. This study could be used by healthcare professionals to understand that individuals who are overweight may choose unhealthy foods due to an imbalance in their gut microbiota. These individuals may benefit from prebiotic fibre to help aid microbiota changes and empowerment over food choices.
Abstract
OBJECTIVE Animal studies suggest that prebiotic, plant-derived nutrients could improve homoeostatic and hedonic brain functions through improvements in microbiome-gut-brain communication. However, little is known if these results are applicable to humans. Therefore, we tested the effects of high-dosed prebiotic fibre on reward-related food decision-making in a randomised controlled within-subject cross-over study and assayed potential microbial and metabolic markers. DESIGN 59 overweight young adults (19 females, 18-42 years, body mass index 25-30 kg/m2) underwent functional task MRI before and after 14 days of supplementary intake of 30 g/day of inulin (prebiotics) and equicaloric placebo, respectively. Short chain fatty acids (SCFA), gastrointestinal hormones, glucose/lipid and inflammatory markers were assayed in fasting blood. Gut microbiota and SCFA were measured in stool. RESULTS Compared with placebo, participants showed decreased brain activation towards high-caloric wanted food stimuli in the ventral tegmental area and right orbitofrontal cortex after prebiotics (preregistered, family wise error-corrected p <0.05). While fasting blood levels remained largely unchanged, 16S-rRNA sequencing showed significant shifts in the microbiome towards increased occurrence of, among others, SCFA-producing Bifidobacteriaceae, and changes in >60 predicted functional signalling pathways after prebiotic intake. Changes in brain activation correlated with changes in Actinobacteria microbial abundance and associated activity previously linked with SCFA production, such as ABC transporter metabolism. CONCLUSIONS In this proof-of-concept study, a prebiotic intervention attenuated reward-related brain activation during food decision-making, paralleled by shifts in gut microbiota. TRIAL REGISTRATION NUMBER NCT03829189.
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Vitamin D supplementation and exercise for improving physical function, body composition and metabolic health in overweight or obese older adults with vitamin D deficiency: a pilot randomized, double-blind, placebo-controlled trial.
Mesinovic, J, Rodriguez, AJ, Cervo, MM, Gandham, A, Xu, CLH, Glavas, C, de Courten, B, Zengin, A, Ebeling, PR, Scott, D
European journal of nutrition. 2023;62(2):951-964
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Overweight and obese older adults are at increased risk for vitamin D deficiency, which is associated with poor metabolic and musculoskeletal health, unfavourable body composition, and attenuated responses to exercise. The aim of this study was to determine whether, compared with placebo, vitamin D3 supplementation (4000 IU/day) taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight or obese older adults with vitamin D deficiency. This study is a 24-week parallel-group, double-blind, placebo-controlled pilot randomised controlled trial. Fifty overweight or obese participants were enrolled for the study, and randomised to either 4000 IU/day of oral vitamin D3 or identical placebo. Results demonstrated that 4000 IU/day vitamin D3 supplementation: - did not affect gait speed when taken with or without exercise, - helped achieve optimal serum 25-hydroxyvitamin D levels and decreased waist circumference (compared with placebo) following multi-modal exercise. - taken alone without exercise reduced stair climb times. However, vitamin D3 supplementation did not have any beneficial effects on other biochemical, body composition or physical function parameters when taken alone or during exercise. Authors conclude that future studies should focus on populations with moderate or severe vitamin D deficiency as they are more likely to experience therapeutic benefits from vitamin D supplementation.
Abstract
PURPOSE Vitamin D supplementation may have non-skeletal health benefits and enhance exercise responsiveness, particularly in those with low vitamin D levels. We determined whether, compared with placebo, vitamin D supplementation taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight and obese older adults with vitamin D deficiency. METHODS Fifty overweight or obese older adults (mean ± SD age: 60 ± 6 years; BMI 30.6 ± 5.7 kg/m2) with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 50 nmol/L) were recruited. Participants were randomly allocated to receive either vitamin D3 (4000 IU/day) or matching placebo for 24 weeks. Between weeks 12 and 24, all participants completed multi-modal exercise three days per week while continuing with vitamin D/placebo. Mean changes in physical function (primary outcome: gait speed), body composition and biochemical parameters at weeks 12 and 24 were compared between groups. RESULTS Vitamin D supplementation, with or without exercise, had no effect on gait speed. From baseline to week 12, vitamin D supplementation increased serum 25(OH)D levels (placebo: 2.5 ± 14.7 nmol/L; treatment: 43.4 ± 18.4 nmol/L; P < 0.001) and reduced stair climb times (placebo: 0.3 ± 1.0 s; treatment: - 0.2 ± 1.0 s; P = 0.046). From 12 to 24 weeks, vitamin D supplementation combined with exercise decreased waist circumference (placebo: 1.3 ± 7.3 cm; treatment: - 3.0 ± 6.1 cm; P = 0.02) and waist-to-hip ratio (placebo: 0.01 ± 0.05; treatment: - 0.03 ± 0.05; P = 0.01) relative to placebo. Vitamin D supplementation, with or without exercise, had no effect on other physical function, body composition or metabolic health outcomes. CONCLUSION Vitamin D supplementation had no effect on most physical function, body composition or metabolic health parameters when taken alone, or during exercise, in overweight or obese older adults with vitamin D deficiency. Vitamin D-related improvements in stair climb times and waist circumference suggest that future trials should explore the effects of vitamin D on muscle power, and its effects on body composition when combined with exercise, in populations with moderate or severe vitamin D deficiency.
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Acute feeding with almonds compared to a carbohydrate-based snack improves appetite-regulating hormones with no effect on self-reported appetite sensations: a randomised controlled trial.
Carter, S, Hill, AM, Buckley, JD, Tan, SY, Rogers, GB, Coates, AM
European journal of nutrition. 2023;62(2):857-866
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Long-term regulation of body weight is controlled by balancing energy intake with energy expenditure. Understanding the role of specific food items and their impact on energy intake may assist in promoting weight reduction and weight loss maintenance for people with obesity. The aim of this study was to compare the effects of eating almonds or a carbohydrate-based snack on appetite-regulating hormones, self-reported appetite ratings, and short-term energy intake. This study is based on data obtained from a parallel arm randomised controlled trial. Participants were males and females, aged between 25 and 65 years who were randomly assigned to either the almond or the snack bar treatment groups based on age, sex and body mass index. Results show that the consumption of almonds resulted in a smaller C-peptide response and a larger glucose-dependent insulinotropic polypeptide [pancreatic hormone], glucagon-like peptide 1 [peptide hormone] (timepoint comparisons only), glucagon and pancreatic polypeptide response compared to consuming an isocaloric carbohydrate-rich snack bar. Furthermore, although not significant, the almond group consumed 300 kJ less energy in the meal challenge, 270 kJ of which came from discretionary foods, which may be a clinically important benefit in weight management. Authors conclude that foods that promote satiety help to regulate energy balance and may assist with weight management. However, future studies should consider testing food dose and composition carefully as the volume of food, its sensory qualities, and the acceptance of the food respective of usual meal patterns, may be important in eliciting a feeling of fullness and satisfaction.
Abstract
PURPOSE Early satiety has been identified as one of the mechanisms that may explain the beneficial effects of nuts for reducing obesity. This study compared postprandial changes in appetite-regulating hormones and self-reported appetite ratings after consuming almonds (AL, 15% of energy requirement) or an isocaloric carbohydrate-rich snack bar (SB). METHODS This is a sub-analysis of baseline assessments of a larger parallel-arm randomised controlled trial in overweight and obese (Body Mass Index 27.5-34.9 kg/m2) adults (25-65 years). After an overnight fast, 140 participants consumed a randomly allocated snack (AL [n = 68] or SB [n = 72]). Appetite-regulating hormones and self-reported appetite sensations, measured using visual analogue scales, were assessed immediately before snack food consumption, and at 30, 60, 90 and 120 min following snack consumption. A sub-set of participants (AL, n = 49; SB, n = 48) then consumed a meal challenge buffet ad libitum to assess subsequent energy intake. An additional appetite rating assessment was administered post buffet at 150 min. RESULTS Postprandial C-peptide area under the curve (AUC) response was 47% smaller with AL compared to SB (p < 0.001). Glucose-dependent insulinotropic polypeptide, glucagon and pancreatic polypeptide AUC responses were larger with AL compared to SB (18%, p = 0.005; 39% p < 0.001; 45% p < 0.001 respectively). Cholecystokinin, ghrelin, glucagon-like peptide-1, leptin and polypeptide YY AUCs were not different between groups. Self-reported appetite ratings and energy intake following the buffet did not differ between groups. CONCLUSION More favourable appetite-regulating hormone responses to AL did not translate into better self-reported appetite or reduced short-term energy consumption. Future studies should investigate implications for longer term appetite regulation. ANZCTR REFERENCE NUMBER ACTRN12618001861246 2018.
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Almond Consumption for 8 Weeks Altered Host and Microbial Metabolism in Comparison to a Control Snack in Young Adults.
Dhillon, J, Newman, JW, Fiehn, O, Ortiz, RM
Journal of the American Nutrition Association. 2023;42(3):242-254
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The consumption of almonds can improve cardiometabolic (CM) health. This study explored the effects of consuming a snack of almonds vs. crackers for 8 weeks on changes in cardiometabolic, microbiome and metabolomics markers in young adults. 73 (41 women and 32 men) young adults took part in this 8-week randomized controlled, parallel-arm intervention study. Blood samples were taken at the beginning, at 4 weeks and then at 8 weeks. The results looked at alternations in many serum metabolites involved in metabolic pathways. They therefore provide a deeper understanding of host carbohydrate, lipid and tocopherol metabolism. The findings also show the interconnections between circulating metabolites and microbial metabolism. This provides further evidence for the impacts of dietary changes on host metabolism and associated changes in gut microbe metabolism.
Abstract
Almond consumption can improve cardiometabolic (CM) health. However, the mechanisms underlying those benefits are not well characterized. This study explored the effects of consuming a snack of almonds vs. crackers for 8 weeks on changes in metabolomic profiles in young adults (clinicaltrials.gov ID: NCT03084003). Participants (n = 73, age: 18-19 years, BMI: 18-41 kg/m2) were randomly assigned to consume either almonds (2 oz/d, n = 38) or an isocaloric control snack of graham crackers (325 kcal/d, n = 35) daily for 8 weeks. Blood samples were collected at baseline prior to and at 4 and 8 weeks after the intervention. Metabolite abundances in the serum were quantified by hydrophilic interaction chromatography quadrupole (Q) time-of-flight (TOF) mass spectrometry (MS/MS), gas chromatography (GC) TOF MS, CSH-ESI (electrospray) QTOF MS/MS, and targeted analyses for free PUFAs, total fatty acids, oxylipins and endocannabinoids. Linear mixed model analyses with baseline-adjustment were conducted, and those results were used for enrichment and network analyses. Microbial community pathway predictions from 16S rRNA sequencing of fecal samples was done using PICRUST2. Almond consumption enriched unsaturated triglycerides, unsaturated phosphatidylcholines, saturated and unsaturated lysophosphatidylcholines, tricarboxylic acids, and tocopherol clusters (p < 0.05). Targeted analyses reveal lower levels of omega-3 total fatty acids (TFAs) overall in the almond group compared to the cracker group (p < 0.05). Microbial amino acid biosynthesis, and amino sugar and nucleotide sugar metabolism pathways were also differentially enriched at the end of the intervention (p < 0.05). The study demonstrates the differential effects of almonds on host tocopherol, lipid, and TCA cycle metabolism with potential changes in microbial metabolism, which may interact with host metabolism to facilitate the CM benefits.
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The Effect of Selenium Supplementation on Clinical Outcomes, Metabolic Profiles, and Pulsatility Index of the Uterine Artery in High-Risk Mothers in Terms of Preeclampsia Screening with Quadruple Test: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial : Selenium and preeclampsia.
Mesdaghinia, E, Shahin, F, Ghaderi, A, Shahin, D, Shariat, M, Banafshe, H
Biological trace element research. 2023;201(2):567-576
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Preeclampsia (PE) is a disease related to high blood pressure during pregnancy, which can result in birth complications and even death of the mother and/or infant. Selenium, which is a nutrient derived from the diet is involved in several processes within the body and levels have shown controversial relationships with PE. This randomised control trial of 60 individuals aimed to determine the effects of selenium supplementation for 12 weeks in women at high risk of PE. The results showed that selenium supplementation helped to alleviate inflammation, which is associated with PE. It also helped to improve blood flow to the uterus, sleep quality, depression, and feelings of anxiety. It was concluded that selenium supplementation for 12 weeks in pregnant women at an increased risk of PE had beneficial effects on factors which may contribute to PE. This study could be used by healthcare professionals to understand that nutrient deficiencies may be involved in poorer outcomes during pregnancy and the importance of recommending a nutrient dense diet and pregnancy vitamins which contain adequate amounts of selenium.
Abstract
Data on the effects of selenium (Se) supplementation on clinical outcomes, metabolic profiles, and pulsatility index (PI) in high-risk mothers in terms of preeclampsia (PE) screening with quadruple tests are scarce. This study evaluated the effects of Se supplementation on clinical outcomes, metabolic profiles, and uterine artery PI on Doppler ultrasound in high-risk mothers in terms of PE screening with quad marker. The current randomized, double-blind, placebo-controlled trial was conducted among 60 high-risk pregnant women screening for PE with quad tests. Participants were randomly allocated into two groups (30 participants each group), received either 200 µg/day Se supplements (as Se amino acid chelate) or placebo from 16 to 18 weeks of pregnancy for 12 weeks. Clinical outcomes, metabolic profiles, and uterine artery PI were assessed at baseline and at the end of trial. Se supplementation resulted in a significant elevation in serum Se levels (β 22.25 µg/dl; 95% CI, 18.3, 26.1; P < 0.001) compared with the placebo. Also, Se supplementation resulted in a significant elevation in total antioxidant capacity (β 82.88 mmol/L; 95% CI, 3.03, 162.73; P = 0.04), and total glutathione (β 71.35 µmol/L; 95% CI, 5.76, 136.94; P = 0.03), and a significant reduction in high-sensitivity C-reactive protein levels (β - 1.52; 95% CI, - 2.91, - 0.14; P = 0.03) compared with the placebo. Additionally, Se supplementation significantly decreased PI of the uterine artery in Doppler ultrasound (β - 0.09; 95% CI, - 0.14, - 0.04; P = 0.04), and a significant improvement in depression (β - 5.63; 95% CI, - 6.97, - 4.28; P < 0.001), anxiety (β - 1.99; 95% CI, - 2.56, - 1.42; P < 0.001), and sleep quality (β - 1.97; 95% CI, - 2.47, - 1.46; P < 0.001). Se supplementation for 12 weeks in high-risk pregnant women in terms of PE screening with quad marker had beneficial effects on serum Se level, some metabolic profiles, uterine artery PI, and mental health. IRCT Registration: htpp:// www.irct.ir ; identifier IRCT20200608047701N1.
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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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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Objectives
The aim of this systematic review was to evaluate the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM).
Methodology
This systematic review is registered with PROSPERO and adhered to PRISMA-2020 guidelines for network meta-analysis
The Cochrane Collaboration’s risk-of-bias tool was used to assess eligible randomised trials
8 prespecified markers identified and assessed in this study : 1) HbA1c (%), 2) fasting blood glucose (mmol/L), 3) total cholesterol (mmol/L), 4) triglycerides (mmol/L), 5) fasting insulin (μIU/mL), 6) HOMA-IR, 7) LDL-c (mmol/L), and 8) HDL-c (mmol/L).
Results
- 170 RCT trials of 14223 participants with T2DM treated with vitamin supplements, mineral supplements, or placebo/no treatment were included
- Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively)
- Vitamin K supplements ranked best in reducing glycated haemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence
- Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%)
- Niacin supplements ranked best in triglyceride reductions and increasing high-density lipo-protein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively)
- Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%).
Conclusion
- Micronutrient supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be efficacious in managing T2DM
- It should be noted that the evidence certainty for all was low.
Clinical practice applications:
- Chromium plays an important role in carbohydrate and lipid metabolism and was the most effective micronutrient for decreasing fasting blood glucose, HbA1c, fasting insulin, and HOMA-IR reductions. More pronounced effects were seen for chromium than vitamin E, vitamin C, niacin, selenium, and magnesium supplements
- Vitamin K was the top-ranked micronutrient in reducing HbA1c and fasting insulin levels. The mechanism through which Vitamin K affects glucose metabolism is proposed as activation of the AMP-activated protein kinase/sirtuin 1, that in turn increases phosphocreatine 3-kinase and glucose transporter 2 to decrease insulin resistance and fasting glucose.
- Vanadium was the top-ranked micronutrient in total cholesterol (TC) reductions, where supplementation dosage should be carefully considered, as vanadium compounds can be moderately or highly toxic. Vanadium supplementation is only recommended in cases of vanadium deficiency or diabetes, hyperlipidemia, and hypertension, where the intake of vanadium from food should be enhanced in preference to supplementation
- Niacin was ranked as the most effective in triglyceride (TG) reductions and increasing HDL cholesterol levels. The dose of niacin could not be determined
- Vitamin E was the top-ranked micronutrient in low-density lipo- protein (LDL) cholesterol reductions.
Considerations for future research:
- Considering the clinical importance of these findings, new research is needed to get better insight into the efficacy of micronutrient supplements in managing T2DM
- Selenium homeostasis, selenoprotein, insulin signaling/secretion, and carbohydrate/lipid metabolism are linked in multiple and complex ways but the authors could not explain why chromium supplementation would lower blood glucose more effectively than selenium supplementation, and suggest more research is needed to clarify this
- While vitamin K status could be an emerging treatment target in T2DM prevention and management, it remains to be determined whether vitamin K supplementation has an advantage over other nutrients in terms of hypoglycemic effect, and further research is necessary
- The beneficial effect of vitamin E and niacin supplements regarding lipid metabolism warrant investigation through more rigorous comparative studies.
Abstract
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
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The effect of synbiotic supplementation on hypothyroidism: A randomized double-blind placebo controlled clinical trial.
Ramezani, M, Reisian, M, Sajadi Hezaveh, Z
PloS one. 2023;18(2):e0277213
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Despite the increased awareness and the improvements in medical management of hypothyroidism; depression, mood disturbance and poor health-related quality of life (QoL) is common among hypothyroid patients. Synbiotics have been advocated as being beneficial to patients with metabolic diseases. Synbiotics are a mixture of probiotics and prebiotics that beneficially affect the host by improving the survival and stimulating the growth of advantageous and health promoting microbial species in the gastrointestinal tract. The aim of this study was to examine whether synbiotic supplementation could enhance depression, QoL, and blood pressure, as well as thyroid hormones in hypothyroid patients. This study is a 10-week parallel design randomised placebo-controlled trial. Participants – adults with hypothyroidism - were randomly assigned to the synbiotic (n = 28) or the placebo (n = 28) group. Results show that following 10 weeks supplementation with synbiotics (500 mg of 10⁹ CFU/g probiotics plus fructo-oligosaccharide) in comparison to placebo does not affect serum thyroid stimulating hormone level and depression. However, it significantly improved blood pressure levels and various domains and areas of QoL. Authors conclude that further clinical trials are needed to assess the effectiveness of a synbiotic supplementation along with the current routine treatment for hypothyroid patients.
Abstract
OBJECTIVE We hypothesize that synbiotic supplementation could modulate the intestinal microbiota and subsequently, improve the condition of hypothyroid patients. METHODS Fifty-six adult hypothyroid patients were recruited to this double-blind, placebo-controlled, randomized clinical trial. The intervention was 10 weeks of synbiotic (500 mg of 109 CFU/g probiotics plus fructo-oligosaccharide, n = 28) compared to placebo (lactose, magnesium stearate, talc, and silicon dioxide, n = 28). Randomization and allocation to trial groups were carried out using random number sequences drawn from https://sealedenvelope.com/. Primary outcomes were serum thyroid stimulating hormone (TSH) and free thyroxine (FT4), and secondary outcomes were depression, quality of life, and blood pressure (BP). P-values< 0.05 were considered statistically significant. RESULTS Analysis on 51 patients who completed the trial showed that TSH and depression (p> 0.05) did not change significantly, while serum FT4 significantly increased in both groups (p = 0.03 and p = 0.02 in symbiotic and placebo respectively). A significant decrease in systolic BP occurred only in the synbiotic group (p = 0.05). Significant improvements occurred regarding different domains and areas of quality of life in the crude and adjusted analysis, including perceived mental health (p = 0.02), bodily pain (p = 0.02), general health perception (p = 0.002), and wellbeing (p = 0.002), which were significantly higher in the synbiotic group. CONCLUSIONS Ten-week supplementation with synbiotic had no favorable effect on depression and TSH, but it improved blood pressure and quality of life in patients with hypothyroidism. More trials are needed to support or reject these findings. TRIAL REGISTRATION IRCT20210926052583N1, Iranian Registry of Clinical Trials (IRCT), registered October 1st, 2021.
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Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention.
Li, S, Yin, S, Ding, H, Shao, Y, Zhou, S, Pu, W, Han, L, Wang, T, Yu, H
Cell proliferation. 2023;56(1):e13346
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Multiple risk factors could lead to the development of liver cancer, one of the most common malignant tumours in the world. These risk factors include hepatitis infection, non-alcoholic fatty liver disease and excessive alcohol consumption. Polyphenols are bioactive compounds with antioxidant, anti-inflammatory, anti-mutagenic, anti-viral, hypoglycaemic, anti-hypertensive, antibacterial and anti-proliferative properties. Polyphenols may be effective in reducing the risk of developing liver cancer by altering the metabolism. This review evaluated the effectiveness of polyphenols in protecting the liver and inhibiting hepatocarcinoma development. In addition, the review evaluated several mechanisms by which polyphenols affect glucose and lipid metabolism and mitochondrial metabolism and reduce the effects of oxidative stress, inflammation and toxic metabolites. Further robust studies are required to assess the beneficial effects of polyphenols as a therapeutic agent, as the current knowledge is limited. However, healthcare professionals can use the results of this study to understand the protective effects of polyphenols against liver disease.
Abstract
BACKGROUND Liver cancer is one of the common malignancies. The dysregulation of metabolism is a driver of accelerated tumourigenesis. Metabolic changes are well documented to maintain tumour growth, proliferation and survival. Recently, a variety of polyphenols have been shown to have a crucial role both in liver disease prevention and metabolism regulation. METHODS We conducted a literature search and combined recent data with systematic analysis to comprehensively describe the molecular mechanisms that link polyphenols to metabolic regulation and their contribution in liver protection and liver cancer prevention. RESULTS Targeting metabolic dysregulation in organisms prevents and resists the development of liver cancer, which has important implications for identifying new therapeutic strategies for the management and treatment of cancer. Polyphenols are a class of complex compounds composed of multiple phenolic hydroxyl groups and are the main active ingredients of many natural plants. They mediate a broad spectrum of biological and pharmacological functions containing complex lipid metabolism, glucose metabolism, iron metabolism, intestinal flora imbalance, as well as the direct interaction of their metabolites with key cell-signalling proteins. A large number of studies have found that polyphenols affect the metabolism of organisms by interfering with a variety of intracellular signals, thereby protecting the liver and reducing the risk of liver cancer. CONCLUSION This review systematically illustrates that various polyphenols, including resveratrol, chlorogenic acid, caffeic acid, dihydromyricetin, quercetin, catechins, curcumin, etc., improve metabolic disorders through direct or indirect pathways to protect the liver and fight liver cancer.