Efficacy of a fish hydrolysate supplement on sleep quality: A randomized, double-blind, placebo-controlled, crossover clinical trial.

BACKGROUND & AIMS: Sleep disturbances are widespread in modern societies and linked to a variety of diseases, creating an urgent need for the development of products that help combat sleep difficulties. One suitable nutritional supplement may be a fish hydrolysate composed of low molecular weight peptides. METHODS: This two-arm, double-blind, randomized, placebo-controlled crossover study investigated the effect of a 4-week fish hydrolysate intervention on sleep in a healthy German population reporting poor sleep quality, assessed with the Pittsburgh Sleep Quality Index (PSQI). Further sleep parameters were measured using an online diary and a wrist wearable device. Additionally, questionnaires related to stress, anxiety, depression, and well-being were evaluated and salivary cortisol and product satisfaction were assessed. RESULTS: The 4-week fish hydrolysate supplementation significantly improved subjective sleep quality measured with the PSQI-score (p = .002). Moreover, individuals reported improvements in sleep efficacy and a reduction in sleep disturbances and daytime sleepiness during fish hydrolysate intake (p = .013, p = .046, p = .004 respectively), but not during placebo phase (all p > .05). No significant intra-individual differences were found between fish hydrolysate and placebo supplementation (p > .05). CONCLUSIONS: Although no significant intra-individual differences were found between fish hydrolysate and placebo supplementation, the significant improvement in subjective sleep quality from baseline to treatment phase suggests that fish hydrolysate is a safe nutritional supplement to support individuals with self-reported sleep problems. CLINICAL TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov with the Identifier NCT04983355.

Oral supplementation with fish cartilage hydrolysate in an adult population suffering from knee pain and function discomfort: results from an innovative approach combining an exploratory clinical study and an ex vivo clinical investigation.

BACKGROUND: Aging is frequently associated with impairments of the musculoskeletal system and many elderly people experience joint discomfort or pain which might reduce their ability to move and consequently alter their quality of life. A beneficial effect of fish cartilage hydrolysate (FCH) on pain and joint function has recently been shown in an ACLT/pMMx osteoarthritis rat model. METHODS: We therefore performed an exploratory, non-comparative, multi-centric clinical trial including 33 subjects with moderate knee joint discomfort and loss of functionality to investigate the efficacy of FCH on their algo-functional status. We further determined the potential health benefit of FCH in an original clinical ex vivo study investigating the role of FCH human metabolites on primary human chondrocytes. RESULTS: FCH significantly improved knee pain and function, as assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS). Moreover, FCH significantly reduced pain at rest and while walking, and patient global assessment (PGA), as assessed by the Visual Analogue Scale (VAS), and improved patients' quality of life (SF-36). FCH metabolites decreased the synthesis of catabolic factors (MMP-13) and pro-inflammatory mediators (NO, PGE2) and limited the inhibitory effect of IL-1ß on the synthesis of cartilage matrix components (GAG and collagen). CONCLUSIONS: Thus, these data provide insights on the mode of action of FCH in humans and contribute to explain how FCH may relieve pain and improve joint function in subjects with knee discomfort. Although these preliminary data need to be confirmed in a randomized controlled trial, they strongly support the potential health benefit of such an active ingredient. TRIAL REGISTRATION: The study was registered on clinicaltrials.gov with the identifier NCT04420091 (09/06/2020).

Dietary Marine Hydrolysate Improves Memory Performance and Social Behavior through Gut Microbiota Remodeling during Aging.

Aging is characterized by a decline in social behavior and cognitive functions leading to a decrease in life quality. In a previous study, we show that a fish hydrolysate supplementation prevents age-related decline in spatial short-term memory and long-term memory and anxiety-like behavior and improves the stress response in aged mice. The aim of this study was to determine the effects of a fish hydrolysate enriched with EPA/DHA or not on the cognitive ability and social interaction during aging and the biological mechanisms involved. We showed for the first time that a fish hydrolysate enriched with EPA/DHA or not improved memory performance and preference for social novelty that were diminished by aging. These changes were associated with the modulation of the gut microbiota, normalization of corticosterone, and modulation of the expression of genes involved in the mitochondrial respiratory chain, circadian clock, neuroprotection, and antioxidant activity. Thus, these changes may contribute to the observed improvements in social behavior and memory and reinforced the innovative character of fish hydrolysate in the prevention of age-related impairments.

Benefits of Circulating Human Metabolites from Fish Cartilage Hydrolysate on Primary Human Dermal Fibroblasts, an Ex Vivo Clinical Investigation for Skin Health Applications.

Due to its significant exposure to stressful environmental factors, the skin undergoes a high remodeling rate over time, which alters not only its appearance but also its functionality. This alteration of the skin, namely photoaging, is characterized by dryness and a loss of elasticity that mainly originates from the dysregulation of dermal fibroblast activities. In order to overcome such tissue outcome, cosmetic products have evolved toward nutricosmetics, thus promoting beauty from within. Among bio-actives of interest, bio-peptides deriving from plant or animal sources may exert various biological activities beyond their nutritional value. However, studies remain mostly descriptive and the mode of action at the cellular level in clinic remains a concern. In a recent clinical trial, it was showed that supplementation with a fish cartilage hydrolysate (FCH) improved signs of chronological and photoaging-induced skin changes in healthy women. Here, using an original ex vivo clinical approach adapted to nutricosmetic purpose, we further demonstrated that this fish cartilage hydrolysate was absorbed and that the circulating metabolites produced in humans following FCH intake stimulate human dermal fibroblast growth, promote specific hyaluronan production, up-regulate elastin synthesis and inhibit MMP-1 and 3 expression along with the enhancement of TGF-ß release. Altogether, these data provide clues on the mechanisms likely contributing to the beneficial impact of FCH on human skin functionality by supporting hydration, elasticity and limiting the expression of catabolic factors involved in photoaging onset.

Fish Hydrolysate Supplementation Prevents Stress-Induced Dysregulation of Hippocampal Proteins Relative to Mitochondrial Metabolism and the Neuronal Network in Mice.

Over the past several decades, stress has dramatically increased in occidental societies. The use of natural resources, such as fish hydrolysates, may be an attractive strategy to improve stress management. Our previous study demonstrated the anxiolytic effects of fish hydrolysate supplementation in mice exposed to acute mild stress by limiting stress-induced corticosterone release and modulating the expression of a number of stress-responsive genes. Here, we explore hippocampal protein modulation induced by fish hydrolysate supplementation in mice submitted to acute mild stress, with the aim of better elucidating the underlying mechanisms. Hippocampi from the same cohort of Balb/c mice supplemented with fish hydrolysate (300 mg·kg-1 body weight) or vehicle daily for seven days before being submitted or not to an acute mild stress protocol (four groups, n = 8/group) were subjected to label-free quantitative proteomics analysis combined with gene ontology data mining. Our results show that fish hydrolysate supplementation prevented the observed stress-induced dysregulation of proteins relative to mitochondrial pathways and the neuronal network. These findings suggest that fish hydrolysate represents an innovative strategy to prevent the adverse effects of stress and participate in stress management.

Dietary Fish Hydrolysate Improves Memory Performance Through Microglial Signature Remodeling During Aging.

Brain aging is characterized by a chronic low-grade inflammation, which significantly impairs cognitive function. Microglial cells, the immunocompetent cells of the brain, present a different phenotype, switching from a homeostatic signature (M0) to a more reactive phenotype called "MGnD" (microglial neurodegenerative phenotype), leading to a high production of pro-inflammatory cytokines. Furthermore, microglial cells can be activated by age-induced gut dysbiosis through the vagus nerve or the modulation of the peripheral immune system. Nutrients, in particular n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides, display powerful immunomodulatory properties, and can thus prevent age-related cognitive decline. The objective of this study was to investigate the effects of n-3 LC-PUFAs and low molecular weight peptides contained in a marine by-product-derived hydrolysate on microglial phenotypes and intestinal permeability and their consequences on cognition in mice. We demonstrated that the hydrolysate supplementation for 8 weeks prevented short- and long-term memory decline during aging. These observations were linked to the modulation of microglial signature. Indeed, the hydrolysate supplementation promoted homeostatic microglial phenotype by increasing TGF-ß1 expression and stimulated phagocytosis by increasing Clec7a expression. Moreover, the hydrolysate supplementation promoted anti-inflammatory intestinal pathway and tended to prevent intestinal permeability alteration occurring during aging. Therefore, the fish hydrolysate appears as an interesting candidate to prevent cognitive decline during aging.

Oral Supplementation with Hydrolyzed Fish Cartilage Improves the Morphological and Structural Characteristics of the Skin: A Double-Blind, Placebo-Controlled Clinical Study.

Collagen and its peptides are natural ingredients used in food supplements and nutricosmetics with the claim of providing benefits for skin health and beauty. In this context, the aim of the present study was to evaluate the clinical efficacy of oral supplementation with hydrolyzed fish cartilage for the improvement of chronological and photoaging-induced skin changes. A total of 46 healthy females aged 45 to 59 years were enrolled and divided into two groups: G1-placebo and G2-oral treatment with hydrolyzed fish cartilage. Measurements of skin wrinkles, dermis echogenicity and thickness, and morphological and structural characteristics of the skin were performed in the nasolabial region of the face before and after a 90-day period of treatment using high-resolution imaging, ultrasound, and reflectance confocal microscopy image analyses. A significant reduction in wrinkles and an increase of dermis echogenicity were observed after a 90-day period of treatment with hydrolyzed fish cartilage compared to the placebo and baseline values. In addition, reflectance confocal microscopy (RCM) image analysis showed improved collagen morphology and reduced elastosis after treatment with hydrolyzed fish cartilage. The present study showed the clinical benefits for the skin obtained with oral supplementation with a low dose of collagen peptides from hydrolyzed fish cartilage.

Oral supplementation with fish cartilage hydrolysate accelerates joint function recovery in rat model of traumatic knee osteoarthritis.

The objective of this study was to evaluate the effects of oral fish cartilage hydrolysate (FCH) on symptoms and joint tissue structure in rat developing osteoarthritis induced surgically. Osteoarthritis was induced in the right knee of mature male Lewis rats (n = 12/group) by surgical transection of the anterior cruciate ligament (ACLT) combined with partial medial meniscectomy (pMMx). Two weeks after surgery, rats were treated orally with either control (sterile H2O) or FCH for four weeks. Pain and function were assessed by dynamic weight-bearing test (incapacitance test), electronic Von Frey (EVF; hindpaw allodynia threshold), and pressure algometer (knee allodynia threshold). Time and groups differences at each time point were evaluated using a mixed model. The histological features were evaluated eight weeks after surgery using OARSI score. Mann-Whitney test nonparametric test was applied to compare OARSI score. ACTL/pMMx surgery significantly reduced weight-bearing and increased allodynia and sensitivity thresholds of the operated paw/knee. Globally, FCH improved these parameters faster, but no significant difference between control and FCH groups was observed. Eight weeks after surgery, rats developed moderate OA lesions. Compared with control, FCH did not significantly modify OA lesion severity assessed using the OARSI score. In this mechanically induced OA model, 4 weeks of supplementation with FCH had no significant effect on cartilage lesion, but tends to accelerate pain relief and joint function recovery. This positive trend may have opened the way for further investigation of FCH as potential treatment of joint discomfort associated with OA.

Fish Hydrolysate Supplementation Containing n-3 Long Chain Polyunsaturated Fatty Acids and Peptides Prevents LPS-Induced Neuroinflammation.

Neuroinflammation constitutes a normal part of the brain immune response orchestrated by microglial cells. However, a sustained and uncontrolled production of proinflammatory factors together with microglial activation contribute to the onset of a chronic low-grade inflammation, leading to neuronal damage and cognitive as well as behavioral impairments. Hence, limiting brain inflammatory response and improving the resolution of inflammation could be particularly of interest to prevent these alterations. Dietary n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides are good candidates because of their immunomodulatory and proresolutive properties. These compounds are present in a fish hydrolysate derived from marine-derived byproducts. In this study, we compared the effect of an 18-day supplementation with this fish hydrolysate to a supplementation with docosahexaenoic acid (DHA) on lipopolysaccharide (LPS)-induced inflammation in mice. In response to peripherally injected LPS, the fish hydrolysate supplementation decreased the hippocampal mRNA expression of the proinflammatory cytokines IL-6 (p < 0.001), IL-1ß (p = 0.0008) and TNF-α (p < 0.0001), whereas the DHA supplementation reduced only the expression of IL-6 (p = 0.004). This decline in proinflammatory cytokine expressions was associated with an increase in the protein expression of IκB (p = 0.014 and p = 0.0054 as compared to the DHA supplementation and control groups, respectively) and to a modulation of microglial activation markers in the hippocampus. The beneficial effects of the fish hydrolysate could be due in part to the switch of the hippocampal oxylipin profile towards a more anti-inflammatory profile as compared to the DHA supplementation. Thus, the valorization of fish byproducts seems very attractive to prevent and counteract neuroinflammation.