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

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 (HbA1c, 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: I2=88%, pQ<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], pMD=0.05; substantial heterogeneity: I2=89%, pQ<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. Graphical abstract Supplementary Information The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-022-05760-z.


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Search strategy 7 Present the full search strategies for all databases, registers and websites, including any filters and limits used. Page 3, Supplementary Table 2 Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.

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Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.

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Data items 10a List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.

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10b List and define all other variables for which data were sought (e.g. participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information. Tables 5,10 Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process. Synthesis methods 13a Describe the processes used to decide which studies were eligible for each synthesis (e.g. tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).

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Page 4 13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.
Page 4 13c Describe any methods used to tabulate or visually display results of individual studies and syntheses. Page 4 13d Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.
Page 4 13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g. subgroup analysis, meta-regression).
Page 4 13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results. Page 4 Reporting bias assessment 14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases). Page 4 Certainty assessment 15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. Page 4

Study selection
16a Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.
Page 4 16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded. Page 4,8 Study characteristics 17 Cite each included study and present its characteristics. Page 4,8 Risk of bias in studies 18 Present assessments of risk of bias for each included study. Supplementary  Table 8, Supplementary Figure 6 Results of individual studies 19 For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g. confidence/credible interval), ideally using structured tables or plots. 20b Present results of all statistical syntheses conducted. If meta-analysis was done, present for each the summary estimate and its precision (e.g. confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect. 20d Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results.   Abbreviations: EPIC=European Prospective Investigation into Cancer and Nutrition a Maximum 4 points awarded for cohort representativeness, selection of non-exposed cohort, exposure assessment, and demonstration outcome not present at baseline b Maximum 3 points awarded for follow-up length, adequacy of follow-up, and outcome assessment c Maximum 2 points awarded for controlling for the pre-specified primary confounding variable (age) and 4 of the 5 secondary (markers of overweight/obesity, family history of diabetes, energy intake, physical activity, sex) confounding variables d A maximum of 9 points could be awarded. Cohorts with NOS ≥6 are considered high quality.   "IHD, Ischemic Heart Disease; A, agency; C, carbohydrate; DA, dietary advice; F, fat; HC, hypercholesterolemia; I, industry; M, men; MetS, metabolic syndrome; ND, Nordic diet intervention; NR, not reported; OB, obese; OW, overweight; P, protein; Suppl, supplemental feeding control; W, women; BW, body weight; WC, waist circumference; TG, triglycerides; ApoB, apoprotein B; SBP and DBP, systolic and diastolic blood pressure; CRP, c-reactive protein. a Supplemental feeding control (Supp) is the provision of some meals and foods consumed during the study. Dietary advice (DA) is the provision of counseling on the appropriate intervention and control diets. b Planned macronutrient composition of intervention and control diets. c Negative energy balance refers to a deficit in normal energy intake and/or intake below energy requirements. Neutral energy balance refers to the maintenance of usual energy intake and/or meeting energy requirements. d For ROB, an assessment was performed using the Cochrane Risk of Bias tool, including the evaluation of individual domains of risk of bias (sequence generation, allocation concealment, blinding of participants/ personnel and outcome assessors, incomplete outcome data, selective outcome reporting). Each of the 5 domains was evaluated as either low, high or unclear ROB and the overall ROB category was determined based on the most selected category. e Agency funding is that from government, university, or not-for-profit sources. Industry funding is that from trade organizations that obtain revenue from the sale of products. * Calculated before dropout ** Non-HDL-C calculated †Finland, Sweden, Denmark, Iceland ESM Table 11. Selected sensitivity analyses in which the systematic removal of an individual trial altered the significance of the effect estimate or the evidence for heterogeneity.    Fig. 6. Risk of bias of included RCTs. Colored bars represent the proportion of studies assessed and circles represent the individual RCT. The colors represent low (green), unclear (yellow) or high (red) risk of bias for the 5 domains of bias above according to criteria set by the Cochrane Risk of Bias tool.