Estimated Change in Colorectal Cancer Risk associated with replacing saturated fats with unsaturated fats.

Background: Colorectal cancer (CRC) is a multifactorial disease responsible for around 2 million new cases and >900,000 deaths annually. Diet is recognized as a major modifiable factor for colorectal cancer, because unlike genetics, dietary patterns are under personal control and can alter CRC risk. The type and source of fat, not just the total fat amount, may affect its development. Saturated fats (SFA) and unsaturated fats (MUFA/PUFA; long-chain ω -3) can influence carcinogenesis via bile-acid signaling, inflammation, gut microbiota changes and lipid metabolism. Aim: My thesis aims to assess whether replacing saturated fatty acids (SFA) with unsaturated fatty acids (UFA) is linked to a lower, higher, or unchanged risk of colorectal cancer (CRC), and whether fat source/profile (animal vs plant; ω -3 vs ω -6) conditions the expected effect of substitution. By exploring this relationship, I seek to better inform dietary guidelines and contribute to the further efforts in CRC prevention. Methods: A structured narrative synthesis of primary analysis was undertaken, complemented by triangulation with secondary and supportive evidence. Studies included in the review used various designs (prospective, case-control, clinical cohorts etc.) to investigate the link between dietary fats and colorectal cancer (CRC) or adenomas. Where formal isocaloric models were absent, approximate substitution was estimated for replacing SFA with MUFA/UFA. I further compared effects by fat source (animal vs. plant) and PUFA subtype. Results: Across the primary evidence, what replaces saturated fatty acids (SFA) is equally important with how much you’re reducing them. For instance, replacements of SFAs with more plant-based and ω-3 fats (long-chain ω-3) led to favorable estimates. Whereas, replacing SFAs with animal-based fats or increasing ω-6 fatty acids without incorporating ω-3s, isn’t likely to show benefits; this approach could even be harmful in certain groups. Triangulation evidence, reinforced the primary analysis, that epidemiological, clinical, and mechanistic research all point to the conclusion: a promising diet to colorectal health is characterized by low saturated fats and high unsaturated fats, rather than just being low in fat. Conclusion: Replacing animal-derived saturated fats for unsaturated fats from marine sources and plant-based options can slightly reduce CRC risk, particularly when ω -3 polyunsaturated fatty acids (PUFAs) are increased and the quality of overall diet is improved. The specific source and profile of the replacement fats are determinative in the success of the substitution. Replacements that lower animal fat and increase unsaturated fats from fish, plant-based oils and nuts are the most defensible strategy for colorectal cancer reduction. Simply exchanging one animal fat for another or increasing ω -6 fats without balancing ω -3 intake is likely ineffective. Ultimately, dietary fat substitution is most effective within an overall plant-forward and fiber-rich dietary pattern. Future targeted studies using explicit isocaloric substitution models and source and subtype-specific fatty-acid exposure analyses, are needed to quantify effects more precisely and deliver targeted food-based guidance.