Nutrimetabolomics uncovers heart-healthy compounds in Mediterranean staple

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In a recently published study, Dr Journal of Nutrition, Researchers in the United States used next-generation nutrimetabolomics methods to characterize the nutrient composition of salmon consumed as part of a Mediterranean-style diet (MED). Liquid Chromatography-Mass Spectrometry (LCMS)-based findings revealed that salmon plays host to 508 food-specific compounds (FSCs), of which 237 are unique. When consumed as part of the MED, salmon provided at least 148 FSCs and 30 metabolites, 4 of which were associated with significant cardiometabolic health indicator (CHI) improvements. In summary, these results highlight the importance of food, especially salmon, as an untapped source of metabolites and other beneficial molecules.

Study: Salmon diet-specific compounds and their metabolites are increased in human plasma and associated with cardiometabolic health indicators following a Mediterranean-style diet intervention.  Image credit: Elena Eryomenko / ShutterstockStudy: Salmon diet-specific compounds and their metabolites are increased in human plasma and associated with cardiometabolic health indices following a Mediterranean-style diet intervention.. Image credit: Elena Eryomenko / Shutterstock

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

Chronic, non-communicable diseases are more prevalent than ever, due to recent poor global lifestyle and dietary changes. A large body of literature predicts that the situation will worsen in the coming years, with pollution, stress and nutritional effects exacerbating the already dire situation. Fortunately, research has also confirmed that the answer to our problems is closer than we think and may be easier than we thought.

Diet (nutrition), sleep and physical activity have been highlighted as the most important behavioral risk determinants of most chronic illnesses, including cardiovascular disease (CVD), neurological problems, mental health problems and cancer. Although studies aimed at identifying individual risk factors and optimizing the outcomes of these ‘health behaviours’ are ongoing, the profound role of these behaviors in the prevention and treatment of common health disorders is unquestioned, and some behaviors (such as regular sleep patterns) are known. Others (such as smoking habits) to be beneficial are not.

Diet choices are directly implicated in the ongoing obesity and overweight epidemic in much of the developed world. Historically, nutrition research has attempted to establish the biochemical values ​​of individual food items and the consequences of their consumption in isolation. More recent work, however, explores dietary patterns, the assemblage of unique food items commonly eaten together, and the synergistic effects of each of those individual components on overall health.

Some diets, such as the Western-style diet, high in fat and sodium while low in fruits and vegetables, have been identified as disease-risk-increasing, while others, such as the Mediterranean-style diet (MED), have been proven disease-causing. – Preventing them from relying on less processed food items and fresh fruits and vegetables. Although 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 exposure. These compounds may serve as objective biomarkers of food intake and/or exert physiological effects. Thus, a comprehensive assessment of the chemical composition of food is “This is an important first step toward improving the assessment of dietary intake and elucidating the mechanistic basis of how dietary intake affects health.”

About the study

In the current study, researchers simultaneously identified key nutrients and metabolites in salmon and conducted a randomized, crossover, controlled feeding trial to investigate the effects of these molecules on obese and overweight patients at risk of CVD. The aim of the study was to use a diet-focused approach to identify potentially novel dietary intake biomarkers. If found, these molecules will be tested for association with CHI in an exploratory fashion.

The study sample included obese and overweight American individuals (BMI 25–37 kg/m2) between the ages of 30 and 69, recruited from Greater Lafayette, Indiana. Inclusion criteria included a medical history free of chronic metabolic disease and current dietary patterns (specifically, current lack of MED). Data collection at baseline was conducted after dietary washout and included fasting blood samples and demographic and medical history. Interventions consisted of two servings per week of salmon (~4–8 oz) (case) and equivalent portions of various unprocessed lean meat items (control).

In parallel, liquid chromatography-mass spectrometry (LCMS) was used to identify the metabolic profile of salmon and 100 other food items commonly included in the MED. The resulting spectrometry data were processed by molecular feature annotation, and in silica Metabolism, predictions were made using a machine learning (ML) framework called Biotransformer. Putative biomarkers identified by the ML model were reviewed and those that met abundance thresholds were extracted from plasma samples using ProFinder.

The identified biomolecules were then subjected to association analysis in which the change in plasma levels of salmon FSCs from the start of the study was calculated from patient plasma samples using a linear mixed-effects model (LMM). If the observed changes were significant, the responsible molecules were repeatedly subjected to tandem mass spectrometry (MMS/MS).

Study results

Salmon characterization analysis showed that the fish contained 508 FSCs. A comparison with 99 other MED food items revealed that 237 metabolites from salmon were unique. Blood plasma analysis identified 106 salmon metabolites and 143 FSCs, all of which were isolated and included as intervention variables in clinical trials.

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

“Previous work suggests that lipids, particularly omega-3 PUFAs, increase with controlled feeding of salmon as well as with fish feeding habits. Higher concentrations of serum PUFA have similarly been associated with overall healthier dietary patterns that include seafood, including the MED diet, the Nordic diet, the DASH diet, and adherence to the US Dietary Guidelines as assessed by the Healthy Eating Index.

Association analyzes 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 clinical metabolites of FSC and use that information to determine the presence and abundance of those predicted metabolites in biospecimens. Their use of a case-control approach highlights the benefits of salmon within the MED and paves the way for future research on other potentially beneficial food items.

“…our results highlight the potential of this comprehensive, nutrimetabolomics-based approach for dietary biomarker identification and testing and suggest strong potential. Additional feeding and follow-up analyzes of future intervention tasks are warranted to assess the quality of these candidate intake biomarkers in salmon. Additional work is needed to assess intake and decline kinetics and to define dose response through acute feeding trials with time-controlled sampling protocols in independent cohorts.”

Journal Reference:

  • Hill, EB, Reisdorph, RM, Rasolofomanana-Rajery, S., Michel, C., Khajeh-Shrafabadi, M., Doenges, KA, Weaver, N., Quinn, K., Sutliff, AK, Tang, M., Borengasser, SJ, Frank, DN, O’Connor, LE, Campbell, WW, Krebs, NF, Hendricks, AE, & Reisdorff, NA (2023). Salmon diet-specific compounds and their metabolites are increased in human plasma and associated with cardiometabolic health indices following a Mediterranean-style diet intervention. Journal of Nutrition, 154(1), 26-40, DOI – 10.1016/j.tjnut.2023.10.024,

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