Sport Sciences Research Institute Sport Physiology 2322-164X 17 65 2025 03 21 Investigating The Association between The RS12722 Polymorphism in The COL5A1 Gene and Omega-3 Supplementation with Flexibility, Strength, and Power in Young Active Men Investigating The Association between The RS12722 Polymorphism in The COL5A1 Gene and Omega-3 Supplementation with Flexibility, Strength, and Power in Young Active Men 71 34 4675 10.22089/spj.2025.17877.2364 FA Seyed Hossein Hosseinimehr Department of Physical Education and Sport Sciences, Faculty of Humanities and Social Sciences, University of Kurdistan, Sanandaj, Kurdistan, Iran 0000-0003-0005-8483 Hassan Faraji Department of Physical Education and Sport Sciences, Mari.C. Islamic Azad University, Marivan, Iran. 0000-0001-5053-7648 Kaiwan Kaki Department of Physical Education and Sport Sciences, Faculty of Humanities and Social Sciences, University of Kurdistan, Sanandaj, Kurdistan, Iran. Journal Article 2025 03 12 Extended Abstract Background and Purpose Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation is well-recognized for its potent anti-inflammatory effects and its essential role in maintaining cellular membrane integrity throughout the body, including connective tissues, where collagen serves as a major structural protein. While collagen endows connective tissues with tensile strength crucial for their function, omega-3 fatty acids indirectly contribute to collagen robustness by attenuating inflammation and potentially stimulating collagen synthesis. Among omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) modulate gene expression through their incorporation into cell membranes and influence over signaling pathways. Although direct evidence linking omega-3 fatty acids to the COL5A gene is limited, existing studies indicate that omega-3s can regulate genes associated with inflammatory responses and collagen metabolism. For instance, modulation of gene expression related to fatty acid metabolic pathways by omega-3s may indirectly influence collagen synthesis and remodeling. Furthermore, omega-3 intake may induce epigenetic modifications affecting collagen-related gene expression, potentially altering the structural and functional characteristics of collagen fibers and ultimately impacting connective tissue integrity. Beyond connective tissue effects, growing interest surrounds omega-3 fatty acids’ positive impact on muscle mass, strength, and physical performance. Despite this, no studies to date have explored the interplay between COL5A genotypes and functional athletic traits such as strength, flexibility, and power, nor assessed how a single course of omega-3 supplementation affects these parameters considering individual genotype. Therefore, this study aimed to examine the association of the COL5A genotype with strength, flexibility, and power among strength-trained athletes and to evaluate the influence of an eight-week omega-3 supplementation protocol on these performance factors. Materials and Methods Out of 93 volunteers initially recruited, 85 participants meeting inclusion criteria were randomly assigned into two groups: omega-3 supplementation (n = 43) and placebo control (n = 42). A double-blind, placebo-controlled design was employed to investigate both the influence of COL5A genotype on physical performance variables and the effect of omega-3 supplementation on these outcomes. In the first session, body composition, flexibility assessments, and blood samples for genotyping were obtained. Strength and power performance tests were conducted during the second and third sessions. Participants received daily supplementation of three gelatin-coated capsules (one each morning, midday, and evening) totaling 3,900 mg of fish oil per day, comprising 3 g of n-3 PUFA (715 mg EPA and 286 mg DHA per capsule). The placebo group received visually identical capsules without active omega-3 content. Supplementation continued for eight weeks, with follow-up tests conducted post-intervention. COL5A rs12722 polymorphism frequencies were checked for Hardy-Weinberg equilibrium using the Chi-square test. Differences among groups and genotypes in flexibility, strength, and power were analyzed using analysis of covariance (ANCOVA) with Bonferroni post hoc comparisons to assess statistical significance at p < 0.05. Data analysis was performed using SPSS version 21. Results Analysis demonstrated that the main effect of time on flexibility was not significant (F=1.42, p=0.26, η²=0.12), whereas the group effect was significant (F=7.56, p=0.02, η²=0.39), indicating differences between omega-3 and placebo groups. The interaction effect of group × time as well as the three-way interaction of group × time × COL5A1 genotype were not statistically significant (p=0.15 and p=0.25, respectively). For strength performance, no significant effects were found for time (F=1.02, p=0.19, η²=0.10), group (F=2.13, p=0.22, η²=0.09), or their interaction (F=0.92, p=0.28, η²=0.08). Notably, the interaction including COL5A1 genotype (group × time × COL5A1) also lacked significance (p=0.43, η²=0.04). Similarly, analysis of power output showed no significant effects for time (F=1.53, p=0.20, η²=0.10), group (F=0.85, p=0.36, η²=0.11), or their interaction (F=0.52, p=0.63, η²=0.08). The three-way interaction incorporating COL5A1 genotype again was not significant (p=0.16, η²=0.13). Importantly, the data indicated that individuals possessing the COL5A1 CC genotype exhibited significantly greater flexibility compared to other genotypes. Conversely, no significant genotype-related differences were observed for strength or power parameters. Moreover, omega-3 supplementation did not significantly affect flexibility, strength, or muscle power, nor did its effects vary based on COL5A1 rs12722 polymorphism status. Conclusion The findings of this study provide preliminary evidence linking the COL5A1 CC genotype with improved flexibility among strength-trained young men, suggesting a genetic influence on this physical trait. However, this relationship does not extend significantly to strength or power performance. Additionally, an eight-week course of omega-3 PUFA supplementation failed to produce measurable improvements in flexibility, strength, or muscle power, regardless of COL5A1 genotype. Collectively, these results underscore the complexity of genetic contributions to musculoskeletal performance and highlight the limited impact of short-term omega-3 supplementation on these specific athletic metrics. Further research with larger cohorts and longer supplementation periods is necessary to more conclusively determine the influence of genetic polymorphisms and nutritional interventions on physical performance. Article Message This study identifies the rs12722 COL5A1 polymorphism as significantly associated with flexibility in active young males. However, a single course of omega-3 supplementation does not result in significant changes in flexibility, strength, or power across different rs12722 alleles. Continued investigation into gene-nutrient interactions affecting athletic traits is warranted. Authors’ Contributions All authors equally contributed to the design, execution, and documentation of this study. Conflicts of Interest The authors declare no conflicts of interest. Acknowledgments The authors sincerely thank all study participants for their cooperation. Extended Abstract Background and Purpose Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation is well-recognized for its potent anti-inflammatory effects and its essential role in maintaining cellular membrane integrity throughout the body, including connective tissues, where collagen serves as a major structural protein. While collagen endows connective tissues with tensile strength crucial for their function, omega-3 fatty acids indirectly contribute to collagen robustness by attenuating inflammation and potentially stimulating collagen synthesis. Among omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) modulate gene expression through their incorporation into cell membranes and influence over signaling pathways. Although direct evidence linking omega-3 fatty acids to the COL5A gene is limited, existing studies indicate that omega-3s can regulate genes associated with inflammatory responses and collagen metabolism. For instance, modulation of gene expression related to fatty acid metabolic pathways by omega-3s may indirectly influence collagen synthesis and remodeling. Furthermore, omega-3 intake may induce epigenetic modifications affecting collagen-related gene expression, potentially altering the structural and functional characteristics of collagen fibers and ultimately impacting connective tissue integrity. Beyond connective tissue effects, growing interest surrounds omega-3 fatty acids’ positive impact on muscle mass, strength, and physical performance. Despite this, no studies to date have explored the interplay between COL5A genotypes and functional athletic traits such as strength, flexibility, and power, nor assessed how a single course of omega-3 supplementation affects these parameters considering individual genotype. Therefore, this study aimed to examine the association of the COL5A genotype with strength, flexibility, and power among strength-trained athletes and to evaluate the influence of an eight-week omega-3 supplementation protocol on these performance factors. Materials and Methods Out of 93 volunteers initially recruited, 85 participants meeting inclusion criteria were randomly assigned into two groups: omega-3 supplementation (n = 43) and placebo control (n = 42). A double-blind, placebo-controlled design was employed to investigate both the influence of COL5A genotype on physical performance variables and the effect of omega-3 supplementation on these outcomes. In the first session, body composition, flexibility assessments, and blood samples for genotyping were obtained. Strength and power performance tests were conducted during the second and third sessions. Participants received daily supplementation of three gelatin-coated capsules (one each morning, midday, and evening) totaling 3,900 mg of fish oil per day, comprising 3 g of n-3 PUFA (715 mg EPA and 286 mg DHA per capsule). The placebo group received visually identical capsules without active omega-3 content. Supplementation continued for eight weeks, with follow-up tests conducted post-intervention. COL5A rs12722 polymorphism frequencies were checked for Hardy-Weinberg equilibrium using the Chi-square test. Differences among groups and genotypes in flexibility, strength, and power were analyzed using analysis of covariance (ANCOVA) with Bonferroni post hoc comparisons to assess statistical significance at p < 0.05. Data analysis was performed using SPSS version 21. Results Analysis demonstrated that the main effect of time on flexibility was not significant (F=1.42, p=0.26, η²=0.12), whereas the group effect was significant (F=7.56, p=0.02, η²=0.39), indicating differences between omega-3 and placebo groups. The interaction effect of group × time as well as the three-way interaction of group × time × COL5A1 genotype were not statistically significant (p=0.15 and p=0.25, respectively). For strength performance, no significant effects were found for time (F=1.02, p=0.19, η²=0.10), group (F=2.13, p=0.22, η²=0.09), or their interaction (F=0.92, p=0.28, η²=0.08). Notably, the interaction including COL5A1 genotype (group × time × COL5A1) also lacked significance (p=0.43, η²=0.04). Similarly, analysis of power output showed no significant effects for time (F=1.53, p=0.20, η²=0.10), group (F=0.85, p=0.36, η²=0.11), or their interaction (F=0.52, p=0.63, η²=0.08). The three-way interaction incorporating COL5A1 genotype again was not significant (p=0.16, η²=0.13). Importantly, the data indicated that individuals possessing the COL5A1 CC genotype exhibited significantly greater flexibility compared to other genotypes. Conversely, no significant genotype-related differences were observed for strength or power parameters. Moreover, omega-3 supplementation did not significantly affect flexibility, strength, or muscle power, nor did its effects vary based on COL5A1 rs12722 polymorphism status. Conclusion The findings of this study provide preliminary evidence linking the COL5A1 CC genotype with improved flexibility among strength-trained young men, suggesting a genetic influence on this physical trait. However, this relationship does not extend significantly to strength or power performance. Additionally, an eight-week course of omega-3 PUFA supplementation failed to produce measurable improvements in flexibility, strength, or muscle power, regardless of COL5A1 genotype. Collectively, these results underscore the complexity of genetic contributions to musculoskeletal performance and highlight the limited impact of short-term omega-3 supplementation on these specific athletic metrics. Further research with larger cohorts and longer supplementation periods is necessary to more conclusively determine the influence of genetic polymorphisms and nutritional interventions on physical performance. Article Message This study identifies the rs12722 COL5A1 polymorphism as significantly associated with flexibility in active young males. However, a single course of omega-3 supplementation does not result in significant changes in flexibility, strength, or power across different rs12722 alleles. Continued investigation into gene-nutrient interactions affecting athletic traits is warranted. Authors’ Contributions All authors equally contributed to the design, execution, and documentation of this study. Conflicts of Interest The authors declare no conflicts of interest. Acknowledgments The authors sincerely thank all study participants for their cooperation.

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