Supplemental Vitamins and Minerals for CVD Prevention and Treatment

The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease outcomes and all-cause mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (multivitamins, vitamins C, D, β-carotene, calcium, and selenium), or increased risk (antioxidant mixtures and niacin [with a statin] for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks

Nordic dietary patterns and cardiometabolic outcomes : a systematic review and meta-analysis of prospective cohort studies and randomised controlled trials

Funding Information: AZ is a part-time research associate at INQUIS Clinical Research (formerly Glycemic Index Laboratories), a contract research organisation, and a consultant for the Glycemic Index Foundation. AJG has received consulting fees from Solo GI Nutrition and an honorarium from the Soy Nutrition Institute. LC was a Mitacs Elevate postdoctoral fellow jointly funded by the Government of Canada and the Canadian Sugar Institute. She was previously employed as a casual clinical coordinator at INQUIS Clinical Research. TAK has received research support from the CIHR, the International Life Science Institute (ILSI) and the National Honey Board. He has been an invited speaker at the Calorie Control Council Annual Meeting for which he received an honorarium. EMC reports grants from the Natural Sciences and Engineering Research Council of Canada and the CIHR while this study was being conducted, has received research support from Lallemand Health Solutions and Ocean Spray, and has received consultant fees and speaker and travel support from Danone and Lallemand Health Solutions (all are outside this study). DR is director of Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases at Merkur University Hospital, Zagreb, Croatia. He is the president of the Croatian Society for Diabetes and Metabolic Disorders of the Croatian Medical Association. He serves as an Executive Committee member of the Croatian Endocrine Society, Croatian Society of Obesity and Croatian Society for Endocrine Oncology. He was a board member and secretary of IDF Europe and is currently the chair of the IDF Young Leaders in Diabetes (YLD) Programme. He has served as an Executive Committee member of the Diabetes and Nutrition Study Group of the EASD and currently serves as an Executive Committee member of the Diabetes and Cardiovascular Disease Study Group of the EASD. He has served as principal investigator or co-investigator in clinical trials for AstraZeneca, Eli Lilly, MSD, Novo Nordisk, Sanofi Aventis, Solvay and Trophos. He has received travel support, speaker fees and honoraria for advisory board engagements and/or consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Belupo, Boehringer Ingelheim, Eli Lilly, LifeScan – Johnson & Johnson, the International Sweeteners Association, Krka, Medtronic, Mediligo, Mylan, Novartis, Novo Nordisk, MSD, Pfizer, Pliva, Roche, Salvus, Sandoz, Solvay, Sanofi Aventis and Takeda. HK is Director of Clinical Research at the Physicians Committee for Responsible Medicine, a non-profit organisation that provides nutrition education and research. JS-S reports serving on the board of and receiving grant support through his institution from the International Nut and Dried Fruit Council (INC) and the Eroski Foundation. He reports serving on the Executive Committee of the Instituto Danone Spain. He reports receiving research support from the Instituto de Salud Carlos III, Spain; Ministerio de Educación y Ciencia, Spain; the Departament de Salut Pública de la Generalitat de Catalunya, Catalonia, Spain; the European Commission; the California Walnut Commission, USA; Patrimonio Comunal Olivarero, Spain; La Morella Nuts, Spain; and Borges, Spain. He reports receiving consulting fees or travel expenses from Danone, the California Walnut Commission, the Eroski Foundation, the Instituto Danone Spain, Nuts for Life, the Australian Nut Industry Council, Nestlé, Abbot and Font Vella y Lanjarón. He is on the Clinical Practice Guidelines Expert Committee of the EASD and served on the Scientific Committee of the Spanish Agency for Food Safety and Nutrition and the Spanish Federation of the Scientific Societies of Food, Nutrition and Dietetics. He is a member of the International Carbohydrate Quality Consortium (ICQC) and an Executive Board Member of the Diabetes and Nutrition Study Group of the EASD. CWCK has received grants or research support from the Advanced Food and Materials Network, Agriculture and Agri-Food Canada (AAFC), the Almond Board of California, Barilla, the CIHR, the Canola Council of Canada, the International Nut and Dried Fruit Council, the International Tree Nut Council Nutrition Research and Education Foundation, Loblaw Brands, the Peanut Institute, Pulse Canada and Unilever. He has received in-kind research support from the Almond Board of California, Barilla, the California Walnut Commission, Kellogg Canada, Loblaw Brands, Nutrartis, Quaker (PepsiCo), the Peanut Institute, Primo, Unico, Unilever, WhiteWave Foods/Danone. He has received travel support and/or honoraria from Barilla, the California Walnut Commission, the Canola Council of Canada, General Mills, the International Nut and Dried Fruit Council, the International Pasta Organization, Lantmannen, Loblaw Brands, the Nutrition Foundation of Italy, the Oldways Preservation Trust, Paramount Farms, the Peanut Institute, Pulse Canada, Sun-Maid, Tate & Lyle, Unilever and White Wave Foods/Danone. He has served on the scientific advisory board for the International Tree Nut Council, International Pasta Organisation, McCormick Science Institute and Oldways Preservation Trust. He is a founding member of the ICQC and an Executive Board Member of the Diabetes and Nutrition Study Group of the EASD, is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the EASD and is a Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. JLS has received research support from the Canadian Foundation for Innovation, the Ontario Research Fund, the Province of Ontario Ministry of Research, Innovation and Science, the CIHR, Diabetes Canada, the American Society for Nutrition (ASN), the International Nut and Dried Fruit Council Foundation, the National Honey Board (US Department of Agriculture [USDA] honey ‘Checkoff’ programme), the Institute for the Advancement of Food and Nutrition Sciences (IAFNS; formerly ILSI North America), Pulse Canada, the Quaker Oats Center of Excellence, the United Soybean Board (USDA soy ‘Checkoff’ programme), the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (established by the Alberta Pulse Growers), the Plant Protein Fund at the University of Toronto (which has received contributions from IFF) and the Nutrition Trialists Fund at the University of Toronto (established by an inaugural donation from the Calorie Control Council). He has received food donations to support RCTs from the Almond Board of California, the California Walnut Commission, the Peanut Institute, Barilla, Unilever/Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, WhiteWave Foods/Danone, Nutrartis and Dairy Farmers of Canada. He has received travel support, speaker fees and/or honoraria from the ASN, Danone, Dairy Farmers of Canada, FoodMinds, Nestlé, Abbott, General Mills, the Comité Européen des Fabricants de Sucre (CEFS), Nutrition Communications, the International Food Information Council (IFIC), the Calorie Control Council and the International Glutamate Technical Committee. He has or has had ad hoc consulting arrangements with Perkins Coie, Tate & Lyle, Phynova and INQUIS Clinical Research. He is a member of the European Fruit Juice Association Scientific Expert Panel and former member of the Soy Nutrition Institute Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, the EASD, the Canadian Cardiovascular Society and Obesity Canada/Canadian Association of Bariatric Physicians and Surgeons. He serves or has served as an unpaid member of the Board of Trustees and an unpaid scientific advisor for the Food, Nutrition, and Safety Program (FNSP) and the Carbohydrates Committee of the IAFNS. He is a member of the ICQC, an Executive Board Member of the Diabetes and Nutrition Study Group of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His spouse is an employee of AB InBev. PM, EV, SBM, VC, US, UR, MU, A-MA, KH and IT declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Funding Information: Open access funding provided by University of Eastern Finland (UEF) including Kuopio University Hospital. The Diabetes and Nutrition Study Group of the EASD commissioned this systematic review and meta-analysis and provided funding and logistical support for meetings as part of the development of the EASD clinical practice guidelines for nutrition therapy. This work was also supported by the Canadian Institutes of Health Research (CIHR; reference no. 129920) through the Canada-wide Human Nutrition Trialists’ Network (NTN). The Diet, Digestive tract, and Disease (3D) Centre, funded through the Canada Foundation for Innovation and the Ministry of Research and Innovation’s Ontario Research Fund, provided the infrastructure for the conduct of this work. PM was funded by a Connaught Fellowship, an Onassis Foundation Fellowship and a Peterborough KM Hunter Charitable Foundation Scholarship. AZ was funded by a Toronto3D Postdoctoral Fellowship Award and a Banting and Best Diabetes Centre (BBDC) Fellowship in Diabetes Care. AJG was funded by a Nora Martin Fellowship in Nutritional Sciences, the Banting & Best Diabetes Centre Tamarack Graduate Award in Diabetes Research, the Peterborough K. M. Hunter Charitable Foundation Graduate Award and an Ontario Graduate Scholarship. LC was funded by a Mitacs Elevate Postdoctoral Fellowship Award. TAK was funded by a Toronto 3D Postdoctoral Fellowship Award. EMC held the Lawson Family Chair in Microbiome Nutrition Research at the Lawson Centre for Child Nutrition, Temerty Faculty of Medicine, University of Toronto. JS-S is partially supported by the Catalan Institution for Research and Advanced Studies (ICREA) under the ICREA Acadèmia programme. JLS was funded by a PSI Graham Farquharson Knowledge Translation Fellowship, Canadian Diabetes Association Clinician Scientist Award, CIHR Institute of Nutrition, Metabolism and Diabetes (INMD)/Canadian Nutrition Society (CNS) New Investigator Partnership Prize and BBDC Sun Life Financial New Investigator Award. Publisher Copyright: © 2022, The Author(s).AIMS/HYPOTHESIS: Nordic dietary patterns that are high in healthy traditional Nordic foods may have a role in the prevention and management of diabetes. To inform the update of the EASD clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of Nordic dietary patterns and cardiometabolic outcomes. METHODS: We searched MEDLINE, EMBASE and The Cochrane Library from inception to 9 March 2021. We included prospective cohort studies and RCTs with a follow-up of ≥1 year and ≥3 weeks, respectively. Two independent reviewers extracted relevant data and assessed the risk of bias (Newcastle-Ottawa Scale and Cochrane risk of bias tool). The primary outcome was total CVD incidence in the prospective cohort studies and LDL-cholesterol in the RCTs. Secondary outcomes in the prospective cohort studies were CVD mortality, CHD incidence and mortality, stroke incidence and mortality, and type 2 diabetes incidence; in the RCTs, secondary outcomes were other established lipid targets (non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides), markers of glycaemic control (HbA 1c, fasting glucose, fasting insulin), adiposity (body weight, BMI, waist circumference) and inflammation (C-reactive protein), and blood pressure (systolic and diastolic blood pressure). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence. RESULTS: We included 15 unique prospective cohort studies (n=1,057,176, with 41,708 cardiovascular events and 13,121 diabetes cases) of people with diabetes for the assessment of cardiovascular outcomes or people without diabetes for the assessment of diabetes incidence, and six RCTs (n=717) in people with one or more risk factor for diabetes. In the prospective cohort studies, higher adherence to Nordic dietary patterns was associated with 'small important' reductions in the primary outcome, total CVD incidence (RR for highest vs lowest adherence: 0.93 [95% CI 0.88, 0.99], p=0.01; substantial heterogeneity: I 2=88%, p Q<0.001), and similar or greater reductions in the secondary outcomes of CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). Inverse dose-response gradients were seen for total CVD incidence, CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). No studies assessed CHD or stroke mortality. In the RCTs, there were small important reductions in LDL-cholesterol (mean difference [MD] -0.26 mmol/l [95% CI -0.52, -0.00], p MD=0.05; substantial heterogeneity: I 2=89%, p Q<0.01), and 'small important' or greater reductions in the secondary outcomes of non-HDL-cholesterol, apolipoprotein B, insulin, body weight, BMI and systolic blood pressure (p<0.05). For the other outcomes there were 'trivial' reductions or no effect. The certainty of the evidence was low for total CVD incidence and LDL-cholesterol; moderate to high for CVD mortality, established lipid targets, adiposity markers, glycaemic control, blood pressure and inflammation; and low for all other outcomes, with evidence being downgraded mainly because of imprecision and inconsistency. CONCLUSIONS/INTERPRETATION: Adherence to Nordic dietary patterns is associated with generally small important reductions in the risk of major CVD outcomes and diabetes, which are supported by similar reductions in LDL-cholesterol and other intermediate cardiometabolic risk factors. The available evidence provides a generally good indication of the likely benefits of Nordic dietary patterns in people with or at risk for diabetes. REGISTRATION: ClinicalTrials.gov NCT04094194. FUNDING: Diabetes and Nutrition Study Group of the EASD Clinical Practice.Peer reviewe

Effect of Replacing Animal Protein with Plant Protein on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Previous research on the effect of replacing sources of animal protein with plant protein on glycemic control has been inconsistent. We therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of this replacement on glycemic control in individuals with diabetes. We searched MEDLINE, EMBASE, and Cochrane databases through 26 August 2015. We included RCTs ≥ 3-weeks comparing the effect of replacing animal with plant protein on HbA1c, fasting glucose (FG), and fasting insulin (FI). Two independent reviewers extracted relevant data, assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2-statistic). Thirteen RCTs (n = 280) met the eligibility criteria. Diets emphasizing a replacement of animal with plant protein at a median level of ~35% of total protein per day significantly lowered HbA1c (MD = −0.15%; 95%-CI: −0.26, −0.05%), FG (MD = −0.53 mmol/L; 95%-CI: −0.92, −0.13 mmol/L) and FI (MD = −10.09 pmol/L; 95%-CI: −17.31, −2.86 pmol/L) compared with control arms. Overall, the results indicate that replacing sources of animal with plant protein leads to modest improvements in glycemic control in individuals with diabetes. Owing to uncertainties in our analyses there is a need for larger, longer, higher quality trials. Trial Registration: ClinicalTrials.gov registration number: NCT02037321

Effects of Replacing Animal Protein with Plant Protein on Glycemic Control in Individuals with Diabetes

The objective was to conduct a systematic review and meta-analysis (SRMA) of randomized controlled trials (RCTs) to assess the effect of replacing animal with plant protein on glycemic control in diabetes and to perform a cross-sectional study using baseline data from 5 RCTs to assess the relationship between replacing animal with plant protein on HbA1c in type 2 diabetes. The SRMA of 12 trials (n=240) showed diets emphasizing replacement of animal with major plant protein sources significantly lowered HbA1c, fasting glucose and fasting insulin compared with control diets. Our cross-sectional study (n=627) showed substitution of animal with plant protein was not associated with HbA1c change. Overall, the results suggest that replacement of animal with plant protein leads to modest improvements in glycemic control in diabetes, however research is needed to address the limitations of our SRMA and lack of agreement with the associations seen in our cross-sectional study.M.Sc

DASH Dietary Pattern and Cardiometabolic Outcomes: An Umbrella Review of Systematic Reviews and Meta-Analyses

Background: The Dietary Approaches to Stop Hypertension (DASH) dietary pattern, which emphasizes fruit, vegetables, fat-free/low-fat dairy, whole grains, nuts and legumes, and limits saturated fat, cholesterol, red and processed meats, sweets, added sugars, salt and sugar-sweetened beverages, is widely recommended by international diabetes and heart association guidelines. Objective: To summarize the available evidence for the update of the European Association of the Study of Diabetes (EASD) guidelines, we conducted an umbrella review of existing systematic reviews and meta-analyses using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach of the relation of the DASH dietary pattern with cardiovascular disease and other cardiometabolic outcomes in prospective cohort studies and its effect on blood pressure and other cardiometabolic risk factors in controlled trials in individuals with and without diabetes. Methods: MEDLINE and EMBASE were searched through 3 January 2019. We included systematic reviews and meta-analyses assessing the relation of the DASH dietary pattern with cardiometabolic disease outcomes in prospective cohort studies and the effect on cardiometabolic risk factors in randomized and non-randomized controlled trials. Two independent reviewers extracted relevant data and assessed the risk of bias of individual studies. The primary outcome was incident cardiovascular disease (CVD) in the prospective cohort studies and systolic blood pressure in the controlled trials. Secondary outcomes included incident coronary heart disease, stroke, and diabetes in prospective cohort studies and other established cardiometabolic risk factors in controlled trials. If the search did not identify an existing systematic review and meta-analysis on a pre-specified outcome, then we conducted our own systematic review and meta-analysis. The evidence was summarized as risk ratios (RR) for disease incidence outcomes and mean differences (MDs) for risk factor outcomes with 95% confidence intervals (95% CIs). The certainty of the evidence was assessed using GRADE. Results: We identified three systematic reviews and meta-analyses of 15 unique prospective cohort studies (n = 942,140) and four systematic reviews and meta-analyses of 31 unique controlled trials (n = 4,414) across outcomes. We conducted our own systematic review and meta-analysis of 2 controlled trials (n = 65) for HbA1c. The DASH dietary pattern was associated with decreased incident cardiovascular disease (RR, 0.80 (0.76&#8315;0.85)), coronary heart disease (0.79 (0.71&#8315;0.88)), stroke (0.81 (0.72&#8315;0.92)), and diabetes (0.82 (0.74&#8315;0.92)) in prospective cohort studies and decreased systolic (MD, &#8722;5.2 mmHg (95% CI, &#8722;7.0 to &#8722;3.4)) and diastolic (&#8722;2.60 mmHg (&#8722;3.50 to &#8722;1.70)) blood pressure, Total-C (&#8722;0.20 mmol/L (&#8722;0.31 to &#8722;0.10)), LDL-C (&#8722;0.10 mmol/L (&#8722;0.20 to &#8722;0.01)), HbA1c (&#8722;0.53% (&#8722;0.62, &#8722;0.43)), fasting blood insulin (&#8722;0.15 &#956;U/mL (&#8722;0.22 to &#8722;0.08)), and body weight (&#8722;1.42 kg (&#8722;2.03 to &#8722;0.82)) in controlled trials. There was no effect on HDL-C, triglycerides, fasting blood glucose, HOMA-IR, or CRP. The certainty of the evidence was moderate for SBP and low for CVD incidence and ranged from very low to moderate for the secondary outcomes. Conclusions: Current evidence allows for the conclusion that the DASH dietary pattern is associated with decreased incidence of cardiovascular disease and improves blood pressure with evidence of other cardiometabolic advantages in people with and without diabetes. More research is needed to improve the certainty of the estimates

Prevention of Type 2 Diabetes by Lifestyle Changes: A Systematic Review and Meta-Analysis

Prevention of type 2 diabetes (T2D) is a great challenge worldwide. The aim of this evidence synthesis was to summarize the available evidence in order to update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy. We conducted a systematic review and, where appropriate, meta-analyses of randomized controlled trials (RCTs) carried out in people with impaired glucose tolerance (IGT) (six studies) or dysmetabolism (one study) to answer the following questions: What is the evidence that T2D is preventable by lifestyle changes? What is the optimal diet (with a particular focus on diet quality) for prevention, and does the prevention of T2D result in a lower risk of late complications of T2D? The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to assess the certainty of the trial evidence. Altogether seven RCTs (N = 4090) fulfilled the eligibility criteria and were included in the meta-analysis. The diagnosis of incident diabetes was based on an oral glucose tolerance test (OGTT). The overall risk reduction of T2D by the lifestyle interventions was 0.53 (95% CI 0.41; 0.67). Most of the trials aimed to reduce weight, increase physical activity, and apply a diet relatively low in saturated fat and high in fiber. The PREDIMED trial that did not meet eligibility criteria for inclusion in the meta-analysis was used in the final assessment of diet quality. We conclude that T2D is preventable by changing lifestyle and the risk reduction is sustained for many years after the active intervention (high certainty of evidence). Healthy dietary changes based on the current recommendations and the Mediterranean dietary pattern can be recommended for the long-term prevention of diabetes. There is limited or insufficient data to show that prevention of T2D by lifestyle changes results in a lower risk of cardiovascular and microvascular complications

Nuts in the Prevention and Management of Type 2 Diabetes

Diabetes is a continuously growing global concern affecting &gt;10% of adults, which may be mitigated by modifiable lifestyle factors. Consumption of nuts and their inclusion in dietary patterns has been associated with a range of beneficial health outcomes. Diabetes guidelines recommend dietary patterns that incorporate nuts; however, specific recommendations related to nuts have been limited. This review considers the epidemiological and clinical evidence to date for the role of nut consumption as a dietary strategy for the prevention and management of type 2 diabetes (T2D) and related complications. Findings suggest nut consumption may have a potential role in the prevention and management of T2D, with mechanistic studies assessing nuts and individual nut-related nutritional constituents supporting this possibility. However, limited definitive evidence is available to date, and future studies are needed to elucidate better the impact of nuts on the prevention and management of T2D

A Double-Blind, Randomized Controlled, Acute Feeding Equivalence Trial of Small, Catalytic Doses of Fructose and Allulose on Postprandial Blood Glucose Metabolism in Healthy Participants: The Fructose and Allulose Catalytic Effects (FACE) Trial

Recent literature suggests that catalytic doses (&le;10 g/meal or 36 g/day) of D-fructose and D-allulose may reduce postprandial blood glucose responses to carbohydrate loads in people with and without type 2 diabetes by inducing glycogen synthesis. To assess the effect of small single doses of fructose and allulose on postprandial blood glucose regulation in response to a 75 g-oral glucose tolerance test (75 g-OGTT) in healthy individuals, we conducted an acute randomized, crossover, equivalence trial in healthy adults. Each participant randomly received six treatments, separated by a minimum one-week washout. Treatments consisted of a 75 g-OGTT with the addition of fructose or allulose at 0 g (control), 5 g or 10 g. A standard 75 g-OGTT protocol was followed with blood samples at &minus;30, 0, 30, 60, 90, 120 min. The primary outcome was the difference in plasma glucose incremental area under the curve (iAUC). A total of 27 participants underwent randomization with data available from 25 participants. Small doses of fructose or allulose did not show a significant effect on plasma glucose iAUC or other secondary markers of postprandial blood glucose regulation in response to a 75 g-OGTT in healthy individuals. These results were limited by the low power to detect a significant difference, owing to greater than expected intra-individual coefficient of variation (CV) in plasma glucose iAUC. Overall, we failed to confirm the catalytic effects of small doses of fructose and allulose in healthy individuals. Future trials may consider recruiting larger sample sizes of healthy individuals. Trial registration: clinicaltrials.gov identifier, NCT02459834