Effect of Isoenergetic Substitution of Cheese with Other Dairy Products on Blood Lipid Markers in the Fasted and Postprandial State: An Updated and Extended Systematic Review and Meta-analysis of Randomized Controlled Trials in Adults

Consumption of fat as part of a cheese matrix may differentially affect blood lipid responses, when compared to other dairy foods. This systematic review was conducted to compare the impact of consuming equal amounts of fat from cheese and other dairy products on blood lipid markers in the fasted and postprandial state. Searches of PubMed (Medline), Cochrane Central and Embase databases were conducted up to mid-June 2022. Eligible human randomized controlled trials (RCTs) investigated the effect of isoenergetic substitution of hard or semi-hard cheese with other dairy products on blood lipid markers. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Random-effects meta-analyses assessed the effect of ≥2 similar dietary replacements on the same blood lipid marker. Of 1,491 identified citations, 10 articles were included (risk of bias: all some concerns). Pooled analyses of 7 RCTs showed a reduction in fasting total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations following ≥ 14 d mean daily intake of 135 g cheese (weighted mean difference (WMD): −0.24 mmol/L; 95% CI: −0.34, −0.15; I2 = 59.8 %, WMD: −0.19 mmol/L; 95% CI: −0.27, −0.12; I2 = 42.8%, and WMD: −0.04 mmol/L; 95% CI: −0.08, −0.00; I2 = 58.6%, respectively) relative to ∼52 g/d butter. We found no evidence of a benefit from replacing cheese for ≥ 14 d with milk on fasting blood lipid markers (n = 2). Limited postprandial RCTs, described in narrative syntheses, suggested that cheese-rich meals may induce differential fed-state lipid responses compared to some other dairy matrix structures, but not butter (n ≤ 2). In conclusion, these findings indicate that dairy fat consumed in the form of cheese has a differential effect on blood lipid responses relative to some other dairy food structures. However, owing to considerable heterogeneity and limited studies, further confirmation from RCTs is warranted. This systematic review protocol was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42022299748

Parent's perception of respiratory syncytial virus and subsequent wheezing burden:A multi-country cross-sectional survey

Background: Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in infants. RSV bronchiolitis is associated with an increased risk of subsequent wheezing. We aimed to document the parents' perception of the link between RSV infection and subsequent wheezing, wheezing-related healthcare and family resources use, and its impact on family daily life. Methods: This cross-sectional online survey enrolled 1200 parents with at least one child ≤6y living in the United States, United Kingdom, Spain, and Italy. Children diagnosed with RSV bronchiolitis before age of 2 years were included in the RSV group, and those never diagnosed with RSV bronchiolitis in the Reference group. Results: The odds of wheezing were 4.5-fold (95%CI 3.5–5.9) higher in the RSV than in the Reference group. The odds increased to 7.7-fold (95%CI 5.4–11.1) among children who were hospitalized, and 9-fold (95%CI 5.1–16.6) among those admitted to pediatric intensive care with RSV bronchiolitis. Similar trends were observed across all countries. In total, 57% of parents reported their child's wheezing to have moderate to severe impact on their emotional well-being, and 53% on their daily life activities and/or social life. 64% of parents reported moderate–severe impact of wheezing on child's quality of sleep and 49% and 46% reported a moderate–severe impact on their children's emotional well-being and physical activities. Conclusions: This survey suggests an association between RSV infection and subsequent wheezing in children across different countries. Wheezing, especially in association with RSV infection, was associated with increased healthcare utilization and costs, and significantly impacted parents' and children daily life.</p

Parent's perception of respiratory syncytial virus and subsequent wheezing burden:A multi-country cross-sectional survey

Background: Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in infants. RSV bronchiolitis is associated with an increased risk of subsequent wheezing. We aimed to document the parents' perception of the link between RSV infection and subsequent wheezing, wheezing-related healthcare and family resources use, and its impact on family daily life. Methods: This cross-sectional online survey enrolled 1200 parents with at least one child ≤6y living in the United States, United Kingdom, Spain, and Italy. Children diagnosed with RSV bronchiolitis before age of 2 years were included in the RSV group, and those never diagnosed with RSV bronchiolitis in the Reference group. Results: The odds of wheezing were 4.5-fold (95%CI 3.5–5.9) higher in the RSV than in the Reference group. The odds increased to 7.7-fold (95%CI 5.4–11.1) among children who were hospitalized, and 9-fold (95%CI 5.1–16.6) among those admitted to pediatric intensive care with RSV bronchiolitis. Similar trends were observed across all countries. In total, 57% of parents reported their child's wheezing to have moderate to severe impact on their emotional well-being, and 53% on their daily life activities and/or social life. 64% of parents reported moderate–severe impact of wheezing on child's quality of sleep and 49% and 46% reported a moderate–severe impact on their children's emotional well-being and physical activities. Conclusions: This survey suggests an association between RSV infection and subsequent wheezing in children across different countries. Wheezing, especially in association with RSV infection, was associated with increased healthcare utilization and costs, and significantly impacted parents' and children daily life.</p

Replacement of dietary saturated with unsaturated fatty acids is associated with beneficial effects on lipidome metabolites: a secondary analysis of a randomized trial

Background: The effects of replacing dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) and/or polyunsaturated fatty acids (PUFAs) on the plasma lipidome in relation to the cardiometabolic disease (CMD) risk is poorly understood. Objectives: We aimed to assess the impact of substituting dietary SFAs with unsaturated fatty acids (UFAs) on the plasma lipidome and examine the relationship between lipid metabolites modulated by diet and CMD risk. Methods: Plasma fatty acid (FA) concentrations among 16 lipid classes (within-class FAs) were measured in a subgroup from the Dietary Intervention and VAScular function (DIVAS) parallel randomized controlled trial (n = 113/195), which consisted of three 16-wk diets enriched in SFAs (target SFA:MUFA:n-6PUFA ratio = 17:11:4% total energy [TE]), MUFAs (9:19:4% TE), or a MUFA/PUFA mixture (9:13:10% TE). Similar lipidomics an- alyses were conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study (specific case/cohorts: n 1⁄4 775/1886 for type 2 diabetes [T2D], n = 551/1671 for cardiovascular disease [CVD]). Multiple linear regression and multivariable Cox models identified within- class FAs sensitive to replacement of dietary SFA with UFA in DIVAS and their association with CMD risk in EPIC-Potsdam. Elastic-net regression models identified within-class FAs associated with changes in CMD risk markers post–DIVAS interventions. Results: DIVAS high-UFA interventions reduced plasma within-class FAs associated with a higher CVD risk in EPIC-Potsdam, especially SFA- containing glycerolipids and sphingolipids (e.g., diacylglycerol (20:0) z-score = -1.08; SE = 0.17; P value < 10-8), whereas they increased those inversely associated with CVD risk. The results on T2D were less clear. Specific sphingolipids and phospholipids were associated with changes in markers of endothelial function and ambulatory blood pressure, whereas higher low-density lipoprotein cholesterol concentrations were characterized by higher plasma glycerolipids containing lauric and stearic acids. Conclusions: These results suggest a mediating role of plasma lipid metabolites in the association between dietary fat and CMD risk. Future research combining interventional and observational findings will further our understanding of the role of dietary fat in CMD etiology. This trial was registered in ClinicalTrials.gov as NCT01478958

Consumption of dairy products and cardiovascular disease risk: results from the French prospective cohort NutriNet-Santé

In France, dairy products contribute to dietary saturated fat intake, of which reduced consumption is often recommended for cardiovascular disease (CVD) prevention. Epidemiological evidence on the association between dairy consumption and CVD risk remains unclear, suggesting either null or inverse associations. This study aimed to investigate the associations between dairy consumption (overall and specific foods) and CVD risk in a large cohort of French adults. This prospective analysis included participants aged ≥ 18 years from the NutriNet-Santé cohort (2009–2019). Daily dietary intakes were collected using 24h-dietary records. Total dairy, milk, cheese, yogurts, fermented and reduced-fat dairy intakes were investigated. CVD cases (n=1,952) included cerebrovascular (n=878 cases) and coronary heart diseases (CHD, n=1,219 cases). Multivariable Cox models were performed to investigate associations. This analysis included n=104,805 French adults (mean age at baseline 42.8 years (SD 14.6), mean follow-up 5.5 years (SD 3.0, i.e. 579,155 persons years). There were no significant associations between dairy intakes and total CVD or CHD risks. However, the consumption of at least 160 g/d of fermented dairy (e.g. cheese and yogurts) was associated with a reduced risk of cerebrovascular diseases compared to intakes below 57 g/d (HR=0.81 [0.66-0.98], p-trend=0.01). Despite being a major dietary source of saturated fats, dairy consumption was not associated with CVD or CHD risks in this study. However, fermented dairy was associated with a lower cerebrovascular disease risk. Robust randomized controlled trials are needed to further assess the impact of consuming different dairy foods on CVD risk and potential underlying mechanisms

Importance of dairy foods as a contributor to dietary saturated fat intake and impact on cardiometabolic disease risk

Public dietary guidelines worldwide recommend that dietary saturated fatty acids (SFAs) do not exceed 10% total energy (%TE), and their replacement with unsaturated fatty acids (UFAs) has been shown to help prevent cardiometabolic disease (CMD). However, research on the impact of dietary SFAs on CMD risk mostly relies on indirect evidence either from intervention studies measuring biomarkers of disease risk, such as fasting lipid profiles, or from observational prospective cohort studies with disease outcomes. In addition, emerging research suggests the impact of dietary SFAs on cardiometabolic health might be modulated by novel CMD risk markers identified by omics approaches, differential effects of individual SFAs, and/or specific food matrix effects. In particular, dairy products contribute to 21% of dietary SFAs intakes in UK adults, but their consumption does not seem to be associated with increased CMD risk according to epidemiological studies. In this context, this PhD thesis aimed to (i) investigate the impact of overall and individual dietary SFAs on medium�term CMD risk markers and long-term CMD risk, and (ii) assess the utility of dairy foods, and more particularly dairy fat, for CMD prevention at a population level. I first assessed the plasma lipidome-mediated impact of isoenergetically replacing dietary SFAs with monounsaturated fatty acids (MUFAs) or a mixture of MUFAs and polyunsaturated fatty acids (PUFAs) on CMD risk markers and long-term CMD risk (Chapter 2). To achieve this, joint lipidomics analyses in a subset of n=113 participants from the DIVAS randomised controlled trial (RCT) and a sub-cohort from the EPIC-Potsdam prospective cohort study (specific case-cohorts: n=1,707 and n=775 cases for type 2 diabetes, n=1,886 and n=551 cases for cardiovascular disease [CVD]) were completed. This secondary analysis showed that UFA-rich diets implemented over 16 weeks to reduce dietary SFAs in the DIVAS RCT significantly reduced the plasma concentrations of SFA-containing glycerolipids (i.e. mono-, di-, and triacylglycerols) and sphingolipids which were associated with long-term CVD risk in the EPIC-Potsdam cohort study. In addition, I identified that increased serum concentrations of low�density lipoprotein cholesterol (LDL-C), an established CMD risk marker, were associated with higher plasma levels of glycerolipids containing lauric (12:0) and stearic acids (18:0). The impact of individual SFAs was further assessed at the dietary level by conducting a systematic literature review and meta-analysis of 44 RCTs which substituted individual dietary SFAs with another fatty acid (FA) or a mixture of UFAs (Chapter 3). In quantitative meta-analyses, I observed reductions in LDL-C concentrations after the replacement of palmitic acid (C16:0) with UFAs (-0.36 mmol/L, 95%CI -0.50 to -0.21, I2=96.0%, n=18 RCTs) or oleic acid (C18:1) (-0.16 mmol/L, 95% CI -0.28 to -0.03, I2=89.6%, n=9 RCTs), with a similar impact on total cholesterol and apolipoprotein B concentrations. Furthermore, I identified important research gaps regarding the impact of individual dietary SFAs on novel CMD risk markers (e.g. markers of inflammation, endothelial activation, and glycaemic control) and the specific effect of short-chain SFAs, lauric acid (12:0), and myristic acid (14:0). To assess the practical applications of reducing dietary SFAs in free-living UK adults, we developed a food-based dietary fat exchange model (the RISSCI-1 study), which aimed to replace dietary SFAs with UFAs by replacing high-fat dairy and high-SFA snacks with commercially available lower-fat dairy foods along with high-UFA cooking oil and snacks into the habitual diets of n=109 UK adult men for 4 weeks (Chapter 4). Participants successfully exchanged 10.4%TE of dietary SFAs with 9.7%TE UFAs, with minimal impact on other nutrients. In addition, participants incorporated the intervention food items without changing their overall dietary habits. Importantly, the analysis of plasma phospholipid fatty acids (PL FAs) in the RISSCI-1 study, along with those performed in the SATgen, DIVAS, and RESET dietary fat intervention studies (Chapter 5), revealed contrasted results on the validity of individual plasma PL FAs as proxies for dairy consumption. In particular, circulating odd-chain SFAs and ruminant trans FAs have been commonly use as biomarkers of intakes in epidemiological studies so far, but only modestly correlate with overall dairy intakes in RCTs and do not seem to accurately capture the intakes of low-fat dairy foods (Chapter 1). Finally, a prospective analysis of the NutriNet-Santé cohort study did not reveal statistically significant associations between overall and specific dairy consumption and overall CVD (n=1,952 cases) or coronary heart disease risk (n=1,219 cases) among n=104,805 French adults (Chapter 6). However, we observed a 19% reduction (HR=0.81, 95%CI 0.66 to 0.98, p-trend=0.01) in cerebrovascular disease risk (n=878 cases) associated with higher intakes (i.e. at least 160 g/d) of fermented dairy foods (i.e. yogurt, cheese, and fermented milk) compared to low intakes (i.e. below 57 g/d). Despite being observational, these results generated new hypotheses on the potential beneficial effects of specific dairy food matrices on CMD risk, which may stem from bioactive peptides, calcium, and the fermentation process. Overall, results from this PhD thesis concur with current dietary guidelines on the reduction of dietary SFAs in favour of UFAs and suggest that their deleterious impact on CMD risk may be modulated by their individual structure and/or their effect on the plasma lipidome. Moreover, these findings provide further evidence supporting the presence of beneficial compounds within the dairy food matrix, which may counterbalance the potential deleterious effects of their SFA content. Nonetheless, further interventional and observational studies are warranted to validate these conclusions, and future research is needed to elucidate the physiological mechanisms underlying the complex interactions between dietary SFAs, the dairy food matrix, and the physiological response to dairy consumption

Effect of isoenergetic substitution of cheese with other dairy products on blood lipid markers in the fasted and postprandial state: an updated and extended systematic review and meta-analysis of randomized controlled trials in adults

International audienceConsumption of fat as part of a cheese matrix may differentially affect blood lipid responses, when compared to other dairy foods. This systematic review was conducted to compare the impact of consuming equal amounts of fat from cheese and other dairy products on blood lipid markers in the fasted and postprandial state. Searches of PubMed (Medline), Cochrane Central and Embase databases were conducted up to mid-June 2022. Eligible human randomized controlled trials (RCTs) investigated the effect of isoenergetic substitution of hard or semi-hard cheese with other dairy products on blood lipid markers. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Random-effects meta-analyses assessed the effect of ≥2 similar dietary replacements on the same blood lipid marker. Of 1,491 identified citations, 10 articles were included (risk of bias: all some concerns). Pooled analyses of 7 RCTs showed a reduction in fasting total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations following ≥ 14 d mean daily intake of 135 g cheese (weighted mean difference (WMD): −0.24 mmol/L; 95% CI: −0.34, −0.15; I2 = 59.8 %, WMD: −0.19 mmol/L; 95% CI: −0.27, −0.12; I2 = 42.8%, and WMD: −0.04 mmol/L; 95% CI: −0.08, −0.00; I2 = 58.6%, respectively) relative to ∼52 g/d butter. We found no evidence of a benefit from replacing cheese for ≥ 14 d with milk on fasting blood lipid markers (n = 2). Limited postprandial RCTs, described in narrative syntheses, suggested that cheese-rich meals may induce differential fed-state lipid responses compared to some other dairy matrix structures, but not butter (n ≤ 2). In conclusion, these findings indicate that dairy fat consumed in the form of cheese has a differential effect on blood lipid responses relative to some other dairy food structures. However, owing to considerable heterogeneity and limited studies, further confirmation from RCTs is warranted

Effect of isoenergetic substitution of cheese with other dairy products on blood lipid markers in the fasted and postprandial state: an updated and extended systematic review and meta-analysis of randomized controlled trials in adults

Consumption of fat as part of a cheese matrix may differentially affect blood lipid responses when compared with other dairy foods. This systematic review was conducted to compare the impact of consuming equal amounts of fat from cheese and other dairy products on blood lipid markers in the fasted and postprandial state. Searches of PubMed (Medline), Cochrane Central and Embase databases were conducted up to mid-June 2022. Eligible human randomized controlled trials (RCTs) investigated the effect of isoenergetic substitution of hard or semi-hard cheese with other dairy products on blood lipid markers. Risk of bias (RoB) was assessed using the Cochrane RoB 2.0 tool. Random-effects meta-analyses assessed the effect of ≥2 similar dietary replacements on the same blood lipid marker. Of 1491 identified citations, 10 articles were included (RoB: all some concerns). Pooled analyses of 7 RCTs showed a reduction in fasting total cholesterol, LDL-C and HDL-C concentrations after ≥14 d mean daily intake of 135 g cheese (weighted mean difference [WMD]: −0.24 mmol/L; 95% confidence interval (CI): −0.34, −0.15; I2 = 59.8%, WMD: −0.19 mmol/L; 95% CI: −0.27, −0.12; I2 = 42.8%, and WMD: −0.04 mmol/L; 95% CI: −0.08, −0.00; I2 = 58.6%, respectively) relative to ∼52 g/d butter. We found no evidence of a benefit from replacing cheese for ≥14 d with milk on fasting blood lipid markers (n = 2). Limited postprandial RCTs, described in narrative syntheses, suggested that cheese-rich meals may induce differential fed-state lipid responses compared with some other dairy matrix structures, but not butter (n ≤ 2). In conclusion, these findings indicate that dairy fat consumed in the form of cheese has a differential effect on blood lipid responses relative to some other dairy food structures. However, owing to considerable heterogeneity and limited studies, further confirmation from RCTs is warranted.  Trial Registration Number: This systematic review protocol was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42022299748.</p

Can individual fatty acids be used as functional biomarkers of dairy fat consumption in relation to cardiometabolic health? A narrative review

In epidemiological studies, dairy food consumption has been associated with minimal effect or decreased risk of some cardiometabolic diseases (CMD). However, current methods of dietary assessment do not provide objective and accurate measures of food intakes. Thus, the identification of valid and reliable biomarkers of dairy intake is an important challenge to best determine the relationship between dairy consumption and health status. This review investigated potential biomarkers of dairy fat consumption, such as odd-chain, trans- and branched-chain fatty acids, which may improve the assessment of full-fat dairy product consumption. Overall, the current use of serum/plasma fatty acids as biomarkers of dairy fat consumption is mostly based on observational evidence, with a lack of well-controlled, dose response intervention studies to accurately assess the strength of the relationship. Circulating odd-chain saturated fatty acids and trans-palmitoleic acid are increasingly studied in relation to CMD risk and seem to be consistently associated with a reduced risk of type 2 diabetes in prospective cohort studies. However, associations with cardiovascular diseases are less clear. Overall, adding less studied fatty acids such as vaccenic and phytanic acids to the current available evidence may provide a more complete assessment of dairy fat intake and minimise potential confounding from endogenous synthesis. Finally, the current evidence base on the direct effect of dairy fatty acids on established biomarkers of CMD risk (e.g. fasting lipid profiles and markers of glycaemic control) mostly derives from cross-sectional, animal, and in vitro studies, and should be strengthened by well-controlled human intervention studies

Consumption of dairy products and cardiovascular disease risk: results from the French prospective cohort NutriNet-Santé

International audienc