Nutrimetabolomics uncovers heart-healthy compounds in Mediterranean staple

In a recent study published in The Journal of Nutrition, researchers in the United States used next-generation nutrimetabolomics approaches to characterize the nutrient content of Salmon consumed as a part of the Mediterranean-style diet (MED). Liquid chromatography-mass spectrometry (LCMS)-based findings revealed that Salmon plays host to 508 food-specific compounds (FSCs), 237 of which were unique. When consumed as a part of MED, Salmon confers at least 148 FSCs and 30 metabolites, 4 of which were associated with significant cardiometabolic health indicator (CHI) improvements. In summary, these findings highlight the importance of diet, specifically Salmon, as an untapped source of metabolites and other beneficial molecules.

Study: Salmon Food-Specific Compounds and Their Metabolites Increase in Human Plasma and Are Associated with Cardiometabolic Health Indicators Following a Mediterranean-Style Diet Intervention. Image Credit: Elena Eryomenko / Shutterstock

The Mediterranean-style diet (MED) and its role in health

Chronic, non-transmittable diseases are more prevalent than ever before, fuelled by recent poor global lifestyle and diet changes. A vast body of literature predicts the situation will worsen further in coming years, with the effects of pollution, stress, and nutrition compounding an already dire state. Thankfully, research has also confirmed that the answer to our problems is closer than we think and may be simpler than we thought.

Diet (nutrition), sleep, and physical activity have been highlighted as the most critical behavioral risk determinants of most chronic ailments, including cardiovascular disease (CVD), neurological distress, mental health issues, and cancers. While studies aiming to characterize individual risk factors and optimize the outcomes of these ‘health behaviors’ are ongoing, the profound role of these behaviors in the prevention and treatment of public health disorders is unquestionable, and some behaviors (like regular sleep patterns) are known to be beneficial while others (like smoking habits) are not.

Diet choices have been directly implicated in ongoing obesity and overweight pandemics in most of the developed world. Historically, nutrition research has attempted to establish the biochemical value of individual food items and the outcomes of their consumption in isolation. More recent work, however, explores dietary patterns, assemblages of unique food items generally consumed together, and the synergistic impacts of each of those individual components on overall health.

Some diets, such as the Western-style diet, rich in fat and sodium while being low in fruits and vegetables, have been identified as disease-risk enhancing, while others, like the Mediterranean-style diet (MED), have been proven disease-preventing on account of their low processed-foods content and dependence on fresh fruits and vegetables. While MED has been shown to improve cardiometabolic health indicators (CHIs), the individual contributions of its common components remain a mystery.

“Foods such as Salmon are composed of thousands of nutritive and non-nutritive compounds that together represent the totality of dietary exposures. These compounds may serve as objective biomarkers of dietary intake and/or may exert physiological effects. Thus, a comprehensive evaluation of the chemical composition of foods is a critical first step to improving the assessment of dietary intake and elucidating the mechanistic underpinnings of how dietary intake affects health.”

About the study

In the present study, researchers simultaneously characterized the key nutrients and metabolics contained within Salmon and carried out a randomized, crossover, controlled feeding trial to investigate the impacts of these molecules on obese and overweight patients at risk of CVD. The study aimed to use a food-centric approach to potentially identify novel food intake biomarkers. If found, these molecules would be tested for associations with CHIs in an exploratory fashion.

The study sample comprised obese and overweight American individuals (BMI 25-37 kg/m²) between the ages of 30 and 69 years, recruited from Greater Lafayette, Indiana. Inclusion criteria comprised a medical history free of chronic metabolic diseases and current dietary patterns (specifically, a current lack of MED). Data collection at baseline was conducted following dietary washout and consisted of fasting blood samples and demographic and medical histories. Interventions comprised two servings of Salmon (~4-8 oz) per week (cases) and an equivalent portion of different unprocessed lean meat items (controls).

In parallel, liquid chromatography-mass spectrometry (LCMS) was used to identify the metabolomic profile of Salmon and 100 other food items commonly included in MEDs. The resultant spectrometry data was processed via molecular feature annotation, and in silica metabolism, predictions were generated using the machine learning (ML) framework called BioTransmormer. Putative biomarkers identified by the ML model were reviewed, and those that met abundance thresholds were extracted from plasma samples using Profinder.

Identified biomolecules were then subject to association analyses wherein the change in the plasma levels of salmon FSCs from study initiation through its end was computed from patient plasma samples using linear mixed-effect models (LMM). If the observed changes were significant, the responsible molecules were subject to repeated tandem mass spectrometry (MMS/MS).

Study findings

Salmon characterization analyses revealed that the fish contains 508 FSCs. Comparisons with 99 other MED food items revealed that 237 of Salmon’s metabolites were unique. Blood plasma analyses detected 106 salmon metabolites and 143 FSCs, all of which were isolated and included as intervention variables in the clinical trial.

Clinical trial results revealed that 48 salmon FSCs and 30 metabolites (28%) had their plasma concentrations significantly increase over the course of the study (five weeks). Most of the identified molecules were found to be lipid-based.

“Previous work suggests lipids, particularly omega-3 PUFAs, are increased after controlled feeding of Salmon as well as with habitual intake of fish. Higher concentrations of serum PUFAs have similarly been associated with overall healthy dietary patterns that contain seafood, including the MED diet, the Nordic diet, the DASH diet, and with adherence to the United States Dietary Guidelines as assessed by the Healthy Eating Index.”

Association analyses on these biomolecules revealed that two FSCs and two metabolites were associated with improved CHI scores, highlighting their cardiovascular benefits. In conclusion, the present study demonstrates the feasibility of using ML models to predict the clinical metabolism of FSCs and use that information to determine the presence and abundance of those predicted metabolites in biospecimens. Their use of the case-control methodology highlights the benefits of Salmon within MED and paves the way for future research on other potentially beneficial food items.

“…our results highlight the feasibility of and suggest strong potential for this comprehensive, nutrimetabolomics-based approach to the identification and testing of food biomarkers. Follow-up analyses of additional foods and future intervention work to assess the quality of these candidate intake biomarkers of Salmon are warranted. Additional work is warranted to evaluate uptake and depletion kinetics and define dose response via acute feeding trials with time-controlled sampling protocols in independent cohorts.”