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Effects of Daily Raspberry Consumption on Immune-Metabolic Health in Subjects at Risk of Metabolic Syndrome: A Randomized Controlled Trial

Maximilien Franck,1,2 Juan de Toro-Martín,1 Véronique Garneau,1 Valérie Guay,1 Michèle Kearney,1 Geneviève Pilon,1,3 Denis Roy,1 Patrick Couture,1,4 Charles Couillard,1,2 André Marette,1,3 and Marie-Claude Vohl1,2,

Abstract

Consumption of red raspberries has been reported to exert acute beneficial effects on postprandial glycemia, insulinemia, triglyceridemia, and cytokine levels in metabolically disturbed subjects. In a two-arm parallel-group, randomized, controlled trial, 59 subjects with overweight or abdominal obesity and with slight hyperinsulinemia or hypertriglyceridemia were randomized to consume 280 g/day of frozen raspberries or to maintain their usual diet for 8 weeks. Primary analyses measured metabolic differences between the groups. Secondary analyses performed with omics tools in the intervention group assessed blood gene expression and plasma metabolomic changes following the raspberry supplementation. The intervention did not significantly affect plasma insulin, glucose, inflammatory marker concentrations, nor blood pressure. Following the supplementation, 43 genes were differentially expressed, and several functional pathways were enriched, a major portion of which were involved in the regulation of cytotoxicity, immune cell trafficking, protein signal transduction, and interleukin production. In addition, 10 serum metabolites were found significantly altered, among which β-alanine, trimethylamine N-oxide, and bioactive lipids. Although the supplementation had no meaningful metabolic effects, these results highlight the impact of a diet rich in raspberry on the immune function and phospholipid metabolism, thus providing novel insights into potential immune-metabolic pathways influenced by regular raspberry consumption.

Keywords: berry fruits, metabolic syndrome, multi-omics, immunity, gene expression, sphingolipids, phenolic compounds

1. Introduction

Both clinical and epidemiological studies highlight the contribution of a plant-food-predominant diet in the maintenance, or even the improvement, of metabolic homeostasis owing to its fiber and phytochemical contents [1]. Long-term consumption of a diet poor in these components constitutes the main predisposing factor to metabolic homeostasis dysregulation [2,3]. Metabolic dysregulations can be seen as a broad range of intermediate phenotypes, all converging with time toward metabolic syndrome, a cluster of interrelated immune-metabolic abnormalities increasing the risk of developing type 2 diabetes or atherosclerotic diseases [4]. Although public health authorities promote plant-food-predominant diets [5], efforts to increase vegetable and fruit consumption have been hardly efficient. Accordingly, it has been demonstrated that dietary habits are difficult to change over the long term [6], highlighting the need to identify simple nutritional interventions that increase the fiber and phytochemical contents of the diet. In this regard, growing evidence has supported the role of berry fruits in the prevention and management of metabolic disorders [7]. Among the most commonly consumed berries, red raspberry (Rb; Rubus idaeus L.) is low in sugar and particularly rich in both fiber and phenolic compounds, mostly anthocyanins, and ellagitannins [8].

Collectively, in vitro and ex vivo research conducted with Rb extracts or purified components have revealed various antioxidative, anti-inflammatory, and metabolic properties through which Rb components may help treat or improve immune-metabolic abnormalities [9,10]. Several animal studies have confirmed these beneficial effects with both Rb components and the entire fruit [11,12,13]. Moreover, some of these studies brought to light the immunomodulatory effects of Rb phenolic compounds [14,15]. Altogether, these results are consistent with those observed with black raspberry (Rubus occidentalis), although of reduced amplitude for an equal amount, presumably attributable to its lower phenolic content [16,17]. Unlike the black raspberry, for which the health-promoting effects have been confirmed in numerous human studies [18,19], very few human randomized controlled intervention studies have been undertaken to assess the health impact of whole Rb or its components, and most of them looked only at the short-term metabolic impact [20,21,22,23,24,25].

In that respect, the aims of this randomized controlled clinical trial were to investigate the health effects of Rb consumption on immune-metabolic features in subjects at risk of developing metabolic syndrome and to delineate the mechanisms underlying these effects through transcriptomics and metabolomics. In the context of personalized nutrition, this holistic approach is part of the efforts undertaken to further understand the impact of foods or nutrients on metabolic syndrome.

Reference:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767072/

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