Food Preservatives and the Rising Tide of Early-Onset Colorectal Cancer: Mechanisms, Controversies, and Emerging Innovations
Abstract
1. Introduction
2. Historical Background of Food Preservatives
2.1. Development of Preservatives in the Food Industry
2.2. Types of Synthetic and Natural Preservatives
2.3. Regulatory Oversight and Classification Systems (e.g., EFSA, FDA)
2.4. The Rise of Natural Preservatives as Alternatives
2.5. Consumption Patterns of Preservatives
3. Epidemiological Link Between Food Preservatives and EOCRC
3.1. Review of Population-Based Studies (USA, Europe, Asia, Africa)
3.2. Case Studies and Global Statistics on EOCRC Trends
3.3. Regional Diets High in Processed Foods vs. Cancer Prevalence
4. Molecular Mechanisms Linking Preservatives to EOCRC
4.1. Genotoxic and Carcinogenic Effects
4.2. Microbiota Dysbiosis and Metabolic Disruption
4.3. Oxidative Stress and Inflammation
4.4. Immune Modulation and Chronic Inflammation
5. Critical Evaluation of Current Studies and Findings
5.1. Conflicting Findings and Ongoing Scientific Debates
5.2. Strengths and Weaknesses in Research Methodologies
5.3. Gaps and Inconsistencies in the Scientific Literature
5.4. In Vitro Evidence
5.5. Animal Studies
5.6. Human Studies
6. Case Studies
6.1. Evidence from Specific Populations and Experimental Models Linking Diet to EOCRC
6.2. Traditional vs. Preserved Food Patterns in Young Adults Diagnosed with CRC
7. Innovations in Preservative Alternatives
Limitations of Natural Preservatives
8. Challenges and Limitations
9. Future Directions
10. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Preservative Name | Type | Mode of Action | Common Applications | Known or Suspected Health Effects | Regulatory Status |
---|---|---|---|---|---|
Sodium nitrite | Synthetic | Antimicrobial, antioxidant | Cured meats (sausages, bacon), processed meats | Nitrosamine formation, genotoxicity | Regulated; limits set by FDA/EFSA [32] |
Sodium nitrate | Synthetic | Antimicrobial precursor | Cured meats, preserved vegetables | Nitrosamine risk under acidic conditions | Regulated [33] |
Sulfites (SO2, K/Na Bisulfite) | Synthetic | Antimicrobial, anti-browning | Dried fruits, wines, soft drinks | Microbiota disruption, potential asthma exacerbation | Allergen labeling required [34] |
BHA/BHT | Synthetic | Lipid oxidation inhibitor | Snack foods, oils, baked goods | Oxidative stress, pro-oxidant effects in vivo | GRAS; debated globally [35] |
Benzoates (sodium benzoate) | Synthetic | Antimicrobial (preserves acids) | Beverages, jams, acidic products | DNA damage, possible microbiota imbalance | E211 (EU); regulated [36] |
Potassium sorbate | Synthetic | Antifungal | Cheese, bakery products | Generally safe; mild irritant in excess | GRAS (FDA), E202 (EU) [37] |
Sorbic acid | Synthetic | Antifungal | Beverages, jams, dairy products | Minimal risk under ADI limits | EFSA acceptable daily intake [38] |
Calcium propionate | Synthetic | Mold inhibitor | Bakery goods | Generally recognized as safe; some behavioral concerns | Extensively studied; GRAS [39] |
Clove oil | Natural | Antimicrobial, antioxidant | Spices, sauces, preserved vegetables | Generally recognized as safe; limited long-term data | Natural additive; regional variation [40] |
Ginger extract | Natural | Antimicrobial, pH modulation | Beverages, marinades, pickles | Minimal adverse effects; efficacy under study | Under review in some jurisdictions [41] |
Nisin | Natural (peptide) | Bacteriocin targeting Gram-positives | Cheese, meat products | Safe, scalable use under investigation | Approved by FDA, EFSA [42] |
Rosemary extract | Natural | Antioxidant, antimicrobial | Oils, dressings, processed meats | Low toxicity; antioxidant-rich | Emerging approval paths [43] |
Green tea polyphenols | Natural | Antioxidant | Beverage preservation, meat systems | Promising safety; efficacy still being studied | Under research for food-grade use [44] |
Category | Examples | Primary Composition | Functional Role in Foods | Associated Health Effects |
---|---|---|---|---|
Synthetic preservatives | Nitrites/nitrates | Inorganic salts (NO2−, NO3−) | Color stabilization in meats; antimicrobial action | May form carcinogenic nitrosamines; linked to gut microbiota disruption [45] |
Benzoates (e.g., sodium benzoate) | Aromatic carboxylic acid derivative | Inhibits yeast, mold, and bacteria | Potential allergic reactions; microbiome alteration [46] | |
Sorbates (e.g., potassium sorbate) | Unsaturated fatty acid salt | Antifungal activity extends shelf life | Generally regarded as safe, but may cause mild irritation at high doses [47] | |
Natural preservatives | Flavonoids (e.g., quercetin, catechins) | Polyphenolic compounds | Antioxidant; antimicrobial; color stabilization | Protective against oxidative stress; gut microbiota modulation [48] |
Tannins | Polyphenolic biomolecules | Astringent; antimicrobial; antioxidant | Potential anti-inflammatory effects; high doses may reduce nutrient absorption [49] | |
Phenolic acids (e.g., gallic acid, ferulic acid) | Hydroxybenzoic and hydroxycinnamic acids | Antimicrobial; antioxidant | May support gut health; anti-inflammatory properties [50] | |
Essential oils (e.g., thymol, carvacrol, eugenol) | Volatile terpenoids and phenylpropanoids | Broad-spectrum antimicrobial; flavor enhancement | Possible anti-inflammatory and immunomodulatory benefits; sensory changes at high concentrations [51] |
Region | Sample Size/Cohort | Focus (Preservatives/Diet Type) | Key Findings | Limitations |
---|---|---|---|---|
France | ~106,000 | Nitrate, nitrite, N-nitroso compounds | Positive association with colorectal cancer (long-term exposure) | Limited to adult CRC, not EOCRC specifically [83] |
USA | 214,797 participants; 3217 CRC cases | Sulfur microbial diet (processed meats, low veg) | HR 1.27 (distal CRC) in the highest quintile of sulfur diet | Not stratified for EOCRC [84] |
Multiple | 26 studies across regions | Western diet, processed meat, sugary drinks | Processed foods are consistent modifiable risk factors in EOCRC | Heterogeneous designs, few preservative-specific data [85] |
UK/global | Experimental/mechanistic | Sodium nitrite servings in the diet | Processed meats linked to CRC pathogenesis in model systems | Animal/mechanistic relevance only [86] |
France | 79,284 women | Food additive nitrites/nitrates | HR ~1.22–1.26 for colorectal cancer (not statistically significant for CRC) | Underpowered for CRC subtype, observational [87] |
Preservative/Group | Study Design & Region | Cohort Size | Risk Estimate (RR/HR/OR, CI) | Key Note |
---|---|---|---|---|
Nitrites/nitrates | Prospective cohort (Europe, EPIC) | ~520,000 | HR 1.17 (95% CI 1.02–1.34) | Processed meat intake linked to CRC risk [88]. |
Sodium benzoate | Case–control (Asia) | ~2500 cases | OR 1.22 (95% CI 1.01–1.48) | Higher intake associated with EOCRC in younger adults [89]. |
Sulphites | Retrospective cohort (Australia) | ~45,000 | RR 1.11 (95% CI 0.97–1.26) | No strong association; signals require more data [90]. |
General processed foods (multiple additives) | Multi-country pooled analysis | >1 million | HR 1.25 (95% CI 1.10–1.40) | Preservative-rich UPFs linked to EOCRC onset [91]. |
Preservative Type | Examples | Relative Risk | Key Concerns/Notes |
---|---|---|---|
High risk | Nitrites, nitrates | High | Formation of carcinogenic N-nitroso compounds; strongly linked to colorectal cancer in epidemiological and animal studies [139]. |
Medium risk | Benzoates | Medium | Potential to disrupt gut microbiota and induce oxidative stress; limited but concerning evidence from in vitro and case–control studies [140]. |
Low risk | Sorbates | Low | Minimal genotoxic or carcinogenic evidence; generally considered safe at regulatory levels [141]. |
Natural preservatives | Fermentation-derived sulfites, plant extracts | Generally low | A safer profile, but risks include allergenicity (sulfites) and inconsistent potency of plant-derived compounds [142]. |
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Mafe, A.N.; Büsselberg, D. Food Preservatives and the Rising Tide of Early-Onset Colorectal Cancer: Mechanisms, Controversies, and Emerging Innovations. Foods 2025, 14, 3079. https://doi.org/10.3390/foods14173079
Mafe AN, Büsselberg D. Food Preservatives and the Rising Tide of Early-Onset Colorectal Cancer: Mechanisms, Controversies, and Emerging Innovations. Foods. 2025; 14(17):3079. https://doi.org/10.3390/foods14173079
Chicago/Turabian StyleMafe, Alice N., and Dietrich Büsselberg. 2025. "Food Preservatives and the Rising Tide of Early-Onset Colorectal Cancer: Mechanisms, Controversies, and Emerging Innovations" Foods 14, no. 17: 3079. https://doi.org/10.3390/foods14173079
APA StyleMafe, A. N., & Büsselberg, D. (2025). Food Preservatives and the Rising Tide of Early-Onset Colorectal Cancer: Mechanisms, Controversies, and Emerging Innovations. Foods, 14(17), 3079. https://doi.org/10.3390/foods14173079