Effect of Omega-3 Fatty Acids on Kynurenine Metabolism and Mood

Overview

The purpose of the current study is to explore the effect of omega-3 fatty acids supplementation on stress-induced changes to kynurenine metabolism and mood. The objectives of this research project are as follows: 1. To compare biochemical parameters (KYN and KYNA, markers of oxidative stress, and markers of inflammation) between physically active and inactive males 2. To determine the impact of a 3-month supplementation with omega-3 fatty acids on mood, inflammation markers and oxidative stress, and changes in KYN and KYNA 3. To determine the impact of the stress manipulation test (TSST) on mood and changes in KYN and KYNA before and after the omega-3 fatty acids supplementation

The purpose of the current study is to explore the effect of omega-3 fatty acids supplementation on stress-induced changes to kynurenine metabolism and mood. While previous studies suggest that peripheral tryptophan conversion to KYN is activated by stress and inflammatory factors, the evidence is based on animal models only. Hence, this will be the first study to test this phenomenon on humans. Omega-3 fatty acids supplementation in this study aims to reduce the inflammatory factors. The stress response in participants will be experimentally controlled by conducting a stress manipulation task. Finally, based on the findings that exercise-induced PGC-1α expression in skeletal muscles might protect against stress-induced neurobiological mechanisms of depressed mood, the study will compare two groups of participants: passive individuals and physically active individuals who might have higher activity of KAT in skeletal muscles. This study design will allow to investigate the effect of long-term endurance training on L-kynurenine levels and mood. Considering a constant rise in the consumed ratio of omega-6/omega-3 as well as a more sedentary lifestyle and higher experienced stress in western countries, this study could have a great therapeutic potential and will expand our understanding of mechanisms of how diet and exercise can influence mood. The objectives of this research project are as follows: 1. To compare biochemical parameters (KYN, KYNA, markers of oxidative stress, and inflammation) between physically active and inactive males 2. To determine the impact of a 3-month supplementation with omega-3 fatty acids on changes in the kynurenine and kynurenic acid 3. To determine the impact of a 3-month supplementation with omega-3 fatty acids on inflammation markers and oxidative stress 4. To determine the impact of a 3-month supplementation with omega-3 fatty acids on mood 5. To determine the impact of the stress manipulation test (TSST) on kynurenine metabolism before and after the omega-3 fatty acids supplementation Procedure Prior to the study, participants will be outlined the study protocol and will be assured about the right to withdrawn at any time. Following this, a written informed consent will be obtained from all participants. Before the start of the intervention blood samples will be collected from the participants to determine the percentage content of omega-3 fatty acids in the serum and red blood cell, KYN and KYNA, markers of oxidative stress (lipid peroxidation products, protein carbonyls), and inflammation markers (CRP, IL-10, TNF). Mood will be assessed using validated psychological measures: Mood Adjective Check List (UMACL) and the Depression, Anxiety and Stress Scale - 21 Items (DASS-21). This will be followed by inducing a stress response with a validated stress manipulation test, the Trier Social Stress Test (TSST) in both groups of participants. After the stress manipulation test, mood and biological parameters will be reassessed. All participants will receive omega-3 supplementation for the period of 12 weeks. 12 weeks after the start of the intervention blood samples will be collected from the participants to determine the omega-3 fatty acid levels, KYN and KYNA, markers of oxidative stress (lipid peroxidation products, protein carbonyls), and inflammation markers (CRP, IL-10, TNF). Mood will be assessed using UMACL and DASS. This will be followed by inducing a stress response (TSST) in both groups of participants. Straight after the stress manipulation test, and 1 hour after the stress manipulation test, mood and biological parameters will be reassessed.