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Objectives: The aim was to systematically review the associations among white meat consumption, cardiovascular diseases (CVD), and type 2 diabetes (T2D). Methods: Databases MEDLINE, Embase, and Cochrane Central Register of Controlled Trials and Scopus were searched (15th October 2021) for randomized intervention trials (RCTs, ≥ 4 weeks of duration) and prospective cohort studies (≥12 month of follow-up) assessing the consumption of white meat as the intervention/exposure. Eligible outcomes for RCTs were cardiometabolic risk factors and for cohorts, fatal and non-fatal CVD and incident T2D. Risk of bias was estimated using the Cochrane’s RoB2 and Risk of Bias for Nutrition Observational Studies. Meta-analysis was conducted in case of ≥3 relevant intervention studies or ≥5 cohort studies using random-effects models. The strength of evidence was evaluated using the World Cancer Research Fund’s criteria. Results: The literature search yielded 5,795 scientific articles, and after screening 43 full-text articles, 23 cohort studies and three intervention studies were included. All included intervention studies matched fat content of intervention and control diets, and none of them showed any significant effects on the selected outcomes of white meat when compared to red meat. Findings from the cohort studies generally did not support any associations between white meat intake and outcomes. Meta-analyses were conducted for CVD mortality (RR: 0.95, 95% CI: 0.87–1.02, P = 0.23, I2 = 25%) and T2D incidence (RR: 0.98, 95% CI: 0.87–1.11, P = 0.81, I2 = 82%). Conclusion: The currently available evidence does not indicate a role, beneficial or detrimental, of white meat consumption for CVD and T2D. Future studies investigating potentially different health effects of processed versus unprocessed white meat and substitution of red meat with white meat are warranted.Registration: Prospero registration CRD42022295915.

Objective: To systematically review the evidence for whether habitual or different levels of experimental intake of vitamin B12 from diet and supplements is sufficient to ensure adequate B12 status in groups most susceptible to vitamin B12 deficiency. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to 21 May 2021, for intervention studies, prospective cohort studies and case-control studies assessing B12 intake from diet and/or supplements in relation to B12 status (s/p-B12, holotranscobalamin, methylmalonic acid, homocysteine or breastmilk B12). Cross-sectional studies were eligible for studies conducted during pregnancy and lactation. Included populations were children (0–18 years), young adults (18–35 years), pregnant or lactating women, older adults (≥65 years) and vegans or vegetarians. Study selection, data extraction and risk of bias assessment were conducted by two assessors independently. The evidence was synthesized qualitatively and classified according to the World Cancer Research Fund. Results: The searches yielded 4855 articles of which 89 were assessed in full text and 18 included. Three studies were conducted during pregnancy and three during lactation or infancy – all observational. Eight studies were conducted among older adults; most were interventions among B12-deficient participants. Four studies were eligible for vegetarian and vegans, all interventions. The strength of evidence that habitual B12 intake or an intake in line with the current Nordic recommended intake (RI) is sufficient to ensure adequate status was considered Limited – no conclusion for all included populations. Conclusion: Evidence is insufficient to assess if or which level of B12 intake is sufficient to maintain adequate status for all included populations. Population-based cohort studies and low-to-moderate dose interventions that address this question are highly warranted.

Objectives: This study aimed to systematically review the evidence for associations between consumption of legumes and cardiovascular disease (CVD), type 2 diabetes (T2D) and their risk factors among healthy adults. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to 16 May 2022 for ≥4 weeks long randomized (RCT) and non-randomized controlled trials and prospective cohort studies with follow-up ≥12 months, assessing legume intake (beans/lentils/peas/soybeans, excluding peanuts and legume-products/protein/powder/flour) as the intervention or exposure. Outcomes were CVD, coronary heart disease (CHD), stroke, T2D and in intervention trials only: changes in blood lipids, glycemic markers, and blood pressure. Risk of bias (RoB) was evaluated with Cochrane’s RoB2, ROBINS-I, and US Department of Agriculture (USDA)’s RoB-NObS. Effect sizes were pooled using random-effects meta-analyses and expressed as relative risk or weighed mean differences with 95% confidence intervals, heterogeneity quantified as I2. The evidence was appraised according to World Cancer Research Fund’s criteria. Results: Of the 181 full-text articles assessed for eligibility, 47 were included: 31 cohort studies (2,081,432 participants with generally low legume consumption), 14 crossover RCTs (448 participants), one parallel RCT and one non-randomized trial. Meta-analyses of cohort studies were suggestive of null associations for CVD, CHD, stroke and T2D. Meta-analyses of RCTs suggested a protective effect on total cholesterol (mean difference −0.22 mmol/L), low density lipoprotein (LDL)-cholesterol (−0.19 mmol/L), fasting glucose (−0.19 mmol/L), and HOMA-IR (−0.30). Heterogeneity was high (I2 = 52% for LDL-cholesterol, >75% for others). The overall evidence for associations between consumption of legumes and risk of CVD and T2D was considered limited – no conclusion. Conclusion: Legume consumption was not found to influence risk of CVD and T2D in healthy adult populations with generally low legume consumption. However, protective effects on risk factors, seen in RCTs, lend some support for recommending legume consumption as part of diverse and healthy dietary patterns for prevention of CVD and T2D.

Background: While dietary fiber intake is low in many children, the current trend to plant-based diets is associated with higher fiber intake in children raised on these diets. As older reports indicate that diets providing high fiber intake in children 0–5 years may affect growth, iron status and bowel function, we summarized the available evidence in this systematic review. Objective: To identify, critically appraise, and synthesize evidence on the effect of high fiber intake on growth, iron and bowel function in children 0–5 years, with relevance to the Nordic and Baltic countries. Methods: Following a pre-registered protocol, we searched MEDLINE, EMBASE, Cochrane Central of Controlled Trials, and Scopus for clinical trials and prospective cohort studies published until November 2021. Two reviewers independently screened retrieved literature, extracted relevant data, and performed risk of bias assessment. Outcomes were growth, iron metabolism and bowel function in children 0–5 years. We narratively described findings from studies that met inclusion criteria. Results: From 5,644 identified records, five articles met the inclusion criteria. Two RCTs had an overall moderate risk of bias, while the three observational studies had serious risk. Overall, we found no robust association between high intake of dietary fiber and growth. In the RCTs, higher intake of fiber had a positive effect on bowel movements and constipation. No studies on fiber intake and iron status were identified.The certainty of the overall evidence was inconclusive for growth and bowel function, while no assessment was made for iron status. Conclusion: We found no clear association between high intake of dietary fiber and growth or bowel function in young children living in affluent countries, albeit with only a limited number of studies. There is a lack of studies investigating health effects of high fiber intake in small children.

Objectives: To systematically review the evidence on the effect of replacing the intake of animal protein with plant protein on cardiovascular disease (CVD) and type 2 diabetes (T2D) and their intermediate risk factors. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to 12th May 2022 for randomized controlled trials (RCTs) or prospective cohort studies that investigated replacement of animal protein with plant protein from foods. Outcomes were CVDs, T2D, and in RCTs also the effects on blood lipids, glycemic markers, and blood pressure. Risk of bias was evaluated with the Cochrane’s RoB2, ROBINS-I, and USDA’s RoB-NObS tools. Random-effects meta-analyses assessed the effects of plant vs. animal proteins on blood lipids in RCTs. The evidence was appraised according to the World Cancer Research Fund’s criteria. Results: After screening 15,090 titles/abstracts, full text of 124 papers was scrutinized in detail, from which 13 RCTs and seven cohort studies were included. Eight of the RCTs had either some concern or high risk of bias, while the corresponding evaluation of cohort studies resulted in moderate risk of bias for all seven. Meta-analyses of RCTs suggested a protective effect on total cholesterol (mean difference -0.11 mmol/L; 95% CI -0.22, -0.01) and low-density lipoprotein cholesterol (-0.14 mmol/L; 95% CI -0.25, -0.02) by replacing animal protein with plant protein. The substitution of animal protein with plant protein (percentage of energy intake) in cohort studies was associated with lower CVD mortality (n = 4) and lower T2D incidence (n = 2). The evidence was considered limited-suggestive for both outcomes. Conclusion: Evidence that the substitution of animal protein with plant protein reduces risk of both CVD mortality and T2D incidence is limited-suggestive. Replacing animal protein with plant protein for aspects of sustainability may also be a public health strategy to lower the risk of CVD mortality and T2D.

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 I2. 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; I2 = 67%), CVD mortality (0.77; 0.72, 0.82; I2 = 59.3%), CHD (0.82; 0.76, 0.89; I2 = 64%), CHD mortality (0.75; 0.65, 0.87; I2 = 66.9%) and non-fatal CHD (0.85; 0.75, 0.96; I2 = 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; I2 = 24.8%) and 0.95 (0.75, 1.21; I2 = 82.2%). Intake of nuts (median ~50 g/day) lowered total (−0.15 mmol/L; −0.22, −0.08; I2 = 31.2%) and LDL-cholesterol (−0.13 mmol/L; −0.21, −0.05; I2 = 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.

Objective: To assess whether supplementation with long chain n-3 fatty acids during pregnancy, lactation, or infancy reduces the risk of developing asthma or atopic disease during childhood. Methods: Searches were performed in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to 2021-09-20, for randomized controlled trials (RCTs) that investigated the effect of supplemental long chain n-3 fatty acids during pregnancy, lactation, or infancy for the prevention of childhood asthma or allergy. Article selection, data extraction, and risk of bias assessment (Cochrane’s Risk of Bias 2.0) were independently conducted by two assessors. The evidence was synthesized qualitatively according to the criteria of the World Cancer Research Fund and meta-analyzed. Results: A total of nine RCTs met inclusion criteria; six were conducted during pregnancy, two during infancy, and one during both pregnancy and infancy. Meta-analysis showed that long chain n-3 fatty acid supplementation during pregnancy significantly reduced the risk of asthma/wheeze in the child (RR 0.62 [95% confidence interval 0.34–0.91], P = 0.005, I2 = 67.4%), but not other outcomes. Supplementation during lactation of infancy showed no effects on any outcome. The strength of evidence that long chain n-3 fatty acid supplementation during pregnancy reduces risk of asthma/wheeze in the offspring was considered limited – suggestive. No conclusion could be made for the effects of long chain n-3 fatty acid supplementation during pregnancy for other atopic diseases, or for supplementation during lactation or infancy for any outcome. Conclusion: The intake of long chain n-3 fatty acid supplements during pregnancy may reduce the risk of asthma and/or wheeze in the offspring, but the strength of evidence is low. There is inconclusive evidence for the effects of long chain n-3 fatty acid supplements during pregnancy for other outcomes, as well as for supplementation during lactation or infancy.

Objective: To identify, critically appraise, and synthesize evidence on the effect of quality of dietary fat intake and different classes of fatty acids on the risk of Alzheimer’s disease (AD) and dementia in adults aged ≥50 years. Methods: We searched MEDLINE, EMBASE, Cochrane Central of Controlled Trials, and Scopus for clinical trials and prospective cohort studies published until May 2021. Two reviewers independently screened retrieved literature, extracted relevant data, and performed risk of bias assessment. Classes of fatty acids included were saturated fatty acids (SFAs), trans fatty acids (TFAs), monounsaturated fatty acids (MUFAs), poly-unsaturated fatty acids (PUFAs), and their subtypes and sources. Given between-study heterogeneity, we did not perform meta-analyses but narratively described findings from the studies. Results: From 4,491 identified records, five articles (based on four prospective cohort studies) met the inclusion criteria. Three studies had an overall serious risk of bias, while one study had a moderate risk. Overall, we found no robust association between intake of any fatty acids type and the development of AD and dementia. For example, for SFA and TFA, there was contradictory associations reported on AD: one study found that each unit increase in energy-adjusted intake of SFA (risk ratio [RR] 0.83, 95%CI 0.70–0.98) and TFA (RR 0.80, 95%CI 0.65–0.97) was associated with a decreased risk of AD, but not dementia. For PUFA, one study found that higher quintile intake of marine-based n-3 PUFA was associated with a decreased risk of AD. The intake of other fatty acids was not associated with the outcomes. The certainty of the overall evidence was inconclusive. Conclusion: We found no clear association between the intake of various classes of fatty acids and the risk of AD and dementia in adults. More well-designed prospective studies are required to clarify these findings.

Objectives: The aim of this study was to examine the evidence for an association between the dietary protein intake in children and the growth and risk of overweight or obesity up to 18 years of age in settings relevant for the Nordic countries. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to February 26, 2021 for randomized controlled trials (RCTs) or prospective cohort studies assessing for protein intake from foods (total and from different sources) in children. The outcomes include weight, height/length, adiposity indices, and/or risk of overweight and/or obesity. The risk of bias was evaluated with instruments for each respective design (Cochrane’s Risk of Bias 2.0 and RoB-NObS). A meta-analysis of five cohort studies was performed. The evidence was classified according to the criteria of the World Cancer Research Fund. Results: The literature search resulted in 9,132 abstracts, of which 55 papers were identified as potentially relevant. In total, 21 studies from 27 publications were included, of which five were RCTs and 16 were cohort studies. The RCTs found generally null effects of high-protein intake in infants on weight gain, nor that lower protein diets negatively affected growth. All included RCTs had some concern regarding the risk of bias and were limited by small sample sizes. Total protein intake and BMI were assessed in 12 cohorts, of which 11 found positive associations. The meta-analysis revealed a pooled effect estimate of 0.06 (95% CI 0.03, 0.1) kg/m2 BMI per one E% increment in total protein (I2 = 15.5). Therefore, the evidence for a positive relationship between total protein intake and BMI was considered probable. Furthermore, there was probable evidence for an association between higher intake of animal protein and increased BMI. There was limited, suggestive evidence for an effect of total protein intake and higher risk of overweight and/or obesity, while no conclusions could be made on the associations between animal vs. plant protein intake and risk of overweight and/or obesity. Discussion: In healthy, well-nourished children of Western populations, there is probably a causal relationship between a high-protein intake in early childhood (≤ 18 months) – particularly protein of animal origin – and higher BMI later in childhood, with consistent findings across cohort studies. A lack of RCTs precluded a stronger grading of the evidence.

Background: The role of micronutrient status for the incidence and clinical course of cutaneous leishmaniasis is not much studied. Still zinc supplementation in leishmaniasis has shown some effect on the clinical recovery, but the evidence in humans is limited. Objective: To compare biochemical nutritional status in cutaneous leishmaniasis patients with that in controls and to study the effects of zinc supplementation for 60 days. Design: Twenty-nine patients with cutaneous leishmaniasis were treated with antimony for 20 days. Fourteen of them got 45 mg zinc daily and 15 of them got placebo. Biomarkers of nutritional and inflammatory status and changes in size and characteristics of skin lesions were measured. Results: The level of transferrin receptor was higher in patients than in controls but otherwise no differences in nutritional status were found between patients and controls. No significant effects of zinc supplementation on the clinical recovery were observed as assessed by lesion area reduction and characteristics or on biochemical parameters. Conclusions: It is concluded that nutritional status was essentially unaffected in cutaneous leishmaniasis and that oral zinc supplementation administered together with intramuscular injection of antimony had no additional clinical benefit.