Plasma Lipidomic Profiles of Dairy Consumption: a New Window on Their Cardiometabolic Effects.

Abstract

HomeHypertensionVol. 79, No. 8Plasma Lipidomic Profiles of Dairy Consumption: a New Window on Their Cardiometabolic Effects Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBPlasma Lipidomic Profiles of Dairy Consumption: a New Window on Their Cardiometabolic Effects Jean-Philippe Drouin-Chartier Jean-Philippe Drouin-ChartierJean-Philippe Drouin-Chartier Correspondence to: Jean-Philippe Drouin-Chartier, Pavillon des Services, Université Laval, 2440 Boulevard Hochelaga, Quebec, QC, Canada, G1V 0A6. Email E-mail Address: [email protected] https://orcid.org/0000-0002-6733-4801 Nutrition, health and society (NUTRISS) Research Center, Institute of Nutrition and Functional Foods (INAF), Laval University, Québec, CA. Faculty of pharmacy, Laval University, Québec, CA. Search for more papers by this author Originally published13 Jul 2022https://doi.org/10.1161/HYPERTENSIONAHA.122.19491Hypertension. 2022;79:1629–1632This article is a commentary on the followingLipidomic Signatures of Dairy Consumption and Associated Changes in Blood Pressure and Other Cardiovascular Risk Factors Among Chinese AdultsSee related article, pp 1617–1628In this issue of Hypertension, the study by Yun et al1 is the latest proof-of-concept of how the use of lipidomics—and, by extension, metabolomics—into nutritional studies contributes to the development of objective dietary assessment methods. The study is also a demonstration of how these approaches foster our understanding of the biochemical pathways underlying the relationship between diet and cardiometabolic health. More specifically, Yun and colleagues identified novel candidate biomarkers of dairy intake and shed light on previously unsuspected biochemical pathways by which the consumption of dairy products may prevents cardiometabolic diseases, all with the use of lipidomics (Figure).Download figureDownload PowerPointFigure. Yun et al1 identified 4 sphingomyelins (SMs) associated with total dairy from 2 independent cohort using a lipidomic panel including 350 lipids. The identification of these 4 SMs served a dual purpose: it allowed to identify novel candidate biomarkers of dairy intake and it shed light on previously unsuspected biochemical pathways by which the consumption of dairy products may prevents cardiometabolic diseases.Briefly, the article reports results from a multi-cohort investigation aiming at (1) identifying plasma lipidomic profiles associated with dairy consumption, (2) characterizing and comparing the relationships between self-reported dairy intake, dairy lipidomic profiles, and subsequent 6-year changes in blood pressure and other cardiometabolic risk factors, and (3) exploring potential causal associations between dairy lipidomic profiles and cardiometabolic risk using Mendelian randomization.1 To identify the plasma lipidomic profiles associated with dairy consumption, investigators conducted agnostic (ie, hypothesis-free) discovery analyses among 2140 adults from the Nutrition and Health of Aging Population in China (NHAPC) study. They subsequently conducted a confirmatory analyses using data from 212 adults that participated in the DPMH trial (Dietary Pattern and Metabolic Health) trial, also conducted in China. In the 2 cohorts, dairy intake was assessed with a food frequency questionnaire inquiring about the intake frequency and amount of milk, milk formula, yogurt, ice cream, and other dairy products over the year preceding its completion. Plasma lipid species were profiled in the 2 cohorts using the same high-throughput targeted liquid chromatograph tandem mass spectrometry method. The panel used for discovery analyses included 350 lipids. It is worth mentioning that conducting such analyses in 2 cohorts from China is of particular interest since the consumption of dairy products in Asian populations is typically lower and less diverse than in American or European populations.Following the discovery analysis in the NHAPC cohort, 26 lipids, mostly sphingomyelins (SMs), triacylglycerols, phosphatidylcholines, and phosphatidylethanolamines, were found to be associated with total dairy intake. Of those, 4 SMs [SM (OH) C32:2, SM C32:1, SM (2OH) C30:2, and SM (OH) C38:2] were also found to be positively associated with total dairy consumption in the DPMH cohort. This finding is of interest in many regards. First, the preponderance of SMs among plasma lipids associated with dairy intake is consistent with the fact that one-third of phospholipids comprised in milk fat globule membranes are SMs. Second, the identification of SM (OH) C32:2 and SM C32:1 as part of the lipidomic profile of dairy intake is consistent with previous studies conducted in cohorts from the United Kingdom, the United States, and Spain that also leveraged agnostic discovery approaches to identify plasma multi-metabolite profiles associated with dairy intake.2–4 The concordance in findings is of particular importance as it supports the external validity of the study by Yun and colleagues in spite of differences with previous investigations in terms of cohort designs, plasma sampling methods, plasma sample storage and storage duration, data collection periods, as well as lifestyles and dietary habits of the cohort participants. Third, the 4 selected SMs exhibited interesting specificity with regard to dairy consumption as they showed null or weak associations with intakes of red meat, soy milk, vegetables, and fruits. Finally, the use of the 4 SMs, alone or in combination, to differentiate individuals with high dairy intakes from those with low intakes showed substantial classification accuracy with C statistics ranging from 0.81 to 0.87. Overall, the 4 selected SMs seem as novel candidate biomarkers of dairy intake.Yun and colleagues also found that plasma levels of the 4 identified SMs were inversely associated with 6-year changes in systolic and diastolic blood pressure, blood glucose and triglyceride concentrations.1 Not only did these associations mirrored the relationship between self-reported dairy intake and 6-year changes in these risk factors, but the SMs also partially mediated the associations between self-reported dairy intake and changes in blood pressure and blood glucose. Furthermore, Mendelian randomization analyses showed that genetically instrumented levels of SM (OH) C32:2, assessed using SPTLC3 gene as the genetic instrument, were inversely associated with systolic and diastolic blood pressure. These results on the relationship between the 4 dairy-related SMs and cardiometabolic health are of great interest in many regards. Indeed, as presented in the discussion of the article, SMs and genetic signals at SPTLC3 locus are known determinants of the blood pressure-lowering effects of hydrochlorothiazide, and many experimental studies have shown how SMs regulate a series of pathways linked to blood pressure and insulin sensitivity. Altogether, these results point toward previously unsuspected SM-mediated biochemical pathways by which the consumption of dairy products may prevent cardiometabolic diseases.The relationship between dairy product consumption and the prevention of cardiometabolic diseases such as hypertension, type 2 diabetes, and cardiovascular diseases has attracted scientific interest for many decades because of the heterogeneity of the nutritional composition of these foods. Indeed, dairy foods contain several bioactive compounds that are suspected to be protective against cardiometabolic diseases.5 Notably, dairy peptides and dairy minerals (ie, calcium, magnesium, potassium) are thought to reduce blood pressure. Dairy minerals are also suspected to attenuate the cholesterol-raising effects of dairy saturated fatty acids. Besides, data suggest that calcium, magnesium, whey protein, milk fat globule membrane, pentadecanoic acid, vitamin D, menaquinone, and lactic acid bacteria enhance insulin sensitivity and/or promote the equilibrium of gut microbiota. On the other hand, dairy products contain diverse fatty acids, mostly saturated, with distinct effects on cardiometabolic health.6 Long, even-chain saturated fatty acids are abundant in dairy fat and increase blood cholesterol and insulin resistance. In contrast, medium- and odd-chain saturated fatty acids and ruminant trans fatty acids are less abundant, but they may improve insulin sensitivity. The study by Yun and colleagues broadens the interest onto dairy nutritional composition by shedding light on the SMs contained in dairy fat, which also appear to have beneficial effects on blood pressure and insulin sensitivity.From an epidemiological point of view, there is substantial evidence reporting that, independent of the dairy fat content, the consumption of dairy products is not associated with the risk of cardiometabolic diseases.7–9 Still, numerous inconsistencies remain, which limits the quality of evidence and, by extent, the ability of public health authorities to translate these data in robust and consensual dietary guidelines. For instance, in a recent systematic review and meta-analysis of prospective cohort studies on the relationship between dairy consumption and cardiometabolic outcomes,9 the consumption of milk or yogurt was found to be associated with a lower risk of hypertension in meta-analyses comparing individuals with high intakes and those with low intakes. However, in dose-response meta-analyses, no evidence of associations between milk or yogurt intake and hypertension risk was found. In that regard, the ability of the nutritional scientific community to objectively assess dairy intake in epidemiological settings remains limited and prone to bias since it primarily relies on subjective memory-based dietary assessment methods. Herein, odd-chain saturated fatty acids are the most commonly used biomarkers of dairy intake.10 Not only odd-chain saturated fatty acids are suspected to have beneficial effects on cardiometabolic health but they have been repeatedly associated with lower risk of cardiometabolic diseases.11 However, their use remains criticized since they lack of specificity with regard to dairy consumption.10,11 Besides, from a clinical standpoint, randomized controlled feeding trials on the impact of dairy consumption on traditional cardiometabolic risk factors (eg, blood pressure, blood lipids, subclinical inflammation, insulin resistance, vascular function) have also been highly inconclusive.12 While meta-analyses of randomized controlled feeding trials found no evidence of potential harmful effects of dairy consumption on traditional cardiometabolic risk factors, no evidence of potential benefits resulting from the consumption of these foods was also reported.13,14 Most importantly, results from RCTs on the impact of dairy consumption on cardiometabolic risk factors are not supportive of those from large prospective cohort studies. Overall, the lack of objective methods to assess dairy consumption in epidemiological settings combined with the inconclusive results from clinical trials evaluating the impact of the consumption of these foods on traditional cardiometabolic risk factors raise legitimate questions not only on their health effects but also on the place they should occupy in a healthy diet.15,16In perspective, the study by Yun and colleagues is, thus, a state-of-the-art demonstration of how profiling the plasma lipid/metabolite profile associated with a dietary exposure—here, dairy products—using agnostic approaches, not limited to a single pathway but instead capturing the inherent complexity of lipid/metabolite networks, contributes to progressively break through this bottleneck. Indeed, lipidomics/metabolomics discovery studies leveraging broad panels of lipids/metabolites allow the identification of candidate biomarkers of dietary intake. This was well exemplified in this study as the 4 identified SMs were associated with dairy intake in 2 independent cohorts while being reflective of dairy fat composition. Moreover, these approaches allow to open new windows on the health effects of diet with the identification of novel potential pathways linking diet to cardiometabolic health, beyond traditional risk factors. The SMs associated with dairy intake that Yun and colleagues identified have previously been shown to be involved in blood pressure and insulin sensitivity regulation which supports the causal biological pathway between dairy intake, the identified lipidomics profile, and the prevention of cardiometabolic diseases. However, it is important to consider that dietary lipidomics or metabolomics profiles identified using observational data are inevitably confounded by the clustering of healthy dietary and lifestyle habits. Also, the objectivity of such dietary lipidomics/metabolomics profiles is, at best, as good as the dietary assessment method used. Therefore, further studies with controlled feeding designs need to be conducted to (1) confirm the validity and specificity of the 4 identified SMs in assessing total dairy intake as well as the consumption of specific dairy foods, (2) determine whether the use of these 4 SMs as biomarkers of dairy intake can complement or should be preferred to the use of plasma odd-chain saturated fatty acids, and (3) confirm that these SMs mediate the impact of dairy consumption on cardiometabolic health. Moving forward and building on multi-cohort approaches, one could envision investigations leveraging fully controlled feeding trials for discovery analyses and observational cohorts for validation analyses to identify highly robust and objective dietary lipidomics or metabolomics profiles while providing novel mechanistic insights. Still, the study by Yun and colleagues constitutes a significant forward step in the identification of objective biomarkers of dairy consumption as well as in our understanding of the biological pathways by which the consumption of these foods may prevent cardiometabolic diseases.Article InformationSources of FundingNone.Disclosures Dr Drouin-Chartier received speaker and consulting honoraria from the Dairy Farmers of Canada in 2016, 2018, and 2021, outside the submitted work.FootnotesThe opinions expressed in this article are not necessarily those of the editors nor the American Heart Association.For Disclosures, see page 1632.Correspondence to: Jean-Philippe Drouin-Chartier, Pavillon des Services, Université Laval, 2440 Boulevard Hochelaga, Quebec, QC, Canada, G1V 0A6. Email jean-philippe.[email protected]ulaval.ca