This systematic review was conducted following the PRISMA 2020 guidelines to ensure the extraction of accurate and reliable information, as well as to promote transparency and comprehensiveness. The study was registered in the Open Science Framework (28). Two researchers independently performed the literature search during the first semester of 2024 and screened the retrieved articles based on titles, abstracts, and full texts. The search was conducted across multiple electronic databases, including PubMed, Scopus, and SciELO.

The PICO framework was used to guide the development of the research question. The Population (P) included adults at risk of developing colorectal cancer; the Intervention (I) was a high-anthocyanin diet; the Comparison (C) was a standard Western diet; and the Outcome (O) was the prevention of colorectal cancer. The formulated research question was: What evidence exists regarding the potential preventive effects of anthocyanin-rich dietary patterns compared with Western dietary patterns on colorectal cancer development when evaluating available in vitro, in vivo, and human studies? Keywords and search terms were defined in both English and Spanish to maximize the comprehensiveness of the search. These included: “anthocyanins,” “colorectal cancer,” “high-anthocyanin diet,” “prevention,” and “Western diet.”

Subsequently, search equations were constructed using Boolean operators, such as: “anthocyanin” OR “anthocyanins” AND “prevention” AND “colorectal cancer” AND “Western diet” AND “effect”.

The inclusion criteria for this review selected studies conducted in adults aged 18 years or older, animal or cell models of colorectal cancer; publications in English or Spanish; articles published from 2018 onward; and original research that specifically investigated anthocyanins and Western diets as the primary variables. Exclusion criteria discarded studies involving individuals with cancers other than colorectal cancer; articles published in languages other than English or Spanish; and non-original research, such as review articles. Only colorectal cancer (CRC) articles were included. Studies focusing exclusively on colon or rectal cancer were not included, even when the same cell lines or experimental models were used.

Data extracted from the selected studies included reported effects of anthocyanins, changes in gut microbiota composition, effects of anthocyanins on colorectal cancer cell proliferation, and outcomes associated with Western dietary patterns. Microsoft Excel was used to organize and manage the article selection process, including the identification of duplicate records and the screening of articles based on their titles and abstracts.

An increasing body of evidence suggests that anthocyanins suppress the initiation and progression of CRC by modulating oxidative stress, inflammatory responses, epigenetic regulation, and gut microbiota composition (Figure 2). Chen et al. (2023) demonstrated that black raspberry (BRB) anthocyanins reduced colorectal tumor development in AOM-induced mouse models and CRC cell lines by modulating histone acetylation. Specifically, BRB anthocyanin treatment led to a global increase in histone acetylation, significantly upregulating the expression of histone acetyltransferases EP300 and MOF, while downregulating the expression of the histone deacetylase SIRT1. This resulted in elevated acetylation levels at histone H4 lysine residues H4K5, H4K12, and H4K16. In addition, BRB anthocyanins downregulated the expression of the anti-apoptotic protein Bcl-2 and cell cycle regulators c-Myc and cyclin D1, while upregulating the pro-apoptotic protein Bax. These molecular changes were associated with activation of the NF-κB signalling pathway, suggesting that BRB anthocyanins promote apoptosis and cell cycle arrest in CRC cells (36). On the other hand, the Andean berry Vaccinium meridionale and its derivatives are recognized for their high content of antioxidant bioactive compounds. However, the fermentation process influences the composition of polyphenols, particularly reducing anthocyanin levels. In comparative analyses, vinegar produced from this berry shows lower antioxidant activity than the original juice, while the alcoholic beverage demonstrates a significantly greater antioxidant effect. Additionally, the vinegar has been shown to inhibit cell proliferation in a concentration-dependent manner in SW480 colon cancer cells (29).

An anthocyanidin mixture derived from bilberry (Anthos) has been reported to suppress the formation of intestinal polyps and tumors in a CRC mouse model. In vivo, anthocyanidin treatment significantly reduced the phosphorylation of Src, EGFR, STAT5, and STAT3, and was accompanied by a reduction in inflammation (34). Similarly, Yu et al. (2021) reported that anthocyanins from Aronia melanocarpa (AMA) exhibit anticancer effects in both in vitro and in vivo CRC models. AMA inhibited Caco-2 cell proliferation and significantly reduced the expression of glutaminase (GLS) and SLC1A5, particularly at 40 mg/kg. This was accompanied by downregulation of mTORC1 signaling proteins, including p-p70S6K, p70S6K, ULK1, p-mTOR, 4EBP1, and p-4EBP1. In a CRC mouse model, AMA similarly suppressed these markers, decreased α-ketoglutarate levels, and reduced tumor malignancy. These findings suggest that AMA inhibits tumor progression by disrupting glutamine metabolism and mTORC1 pathway activation (35). On the other hand, Wei et al. (2020) reported that treatment with AMA reduced cell viability and increased cell death in Caco-2 cells by inducing apoptosis and blocking S-phase progression in a concentration-dependent manner. AMA downregulated the expression of Survivin, c-Myc, and Cyclin D1, while upregulating pro-apoptotic markers such as Bax, cleaved caspase-3, and cytochrome c. Bcl-2 expression was significantly decreased. AMA also promoted the degradation of intracellular free β-catenin without affecting its transcription or translation. This effect was mediated by inhibition of GSK3β phosphorylation, thereby precluding signaling via the Wnt/b-catenin pathway (30).

Tsai et al. (2023) reported that anthocyanin extracts from Hibiscus sabdariffa induce apoptosis in CRC cells by upregulating pro-apoptotic Bcl-2 family members (tBid, Bax, Bad), increasing the levels of apoptosis-inducing factor (AIF) and cytochrome c levels, and reducing Bcl-xL expression. They also activated the Fas/FasL pathway and downstream caspases (3, 8, 9, and PARP), while disrupting mitochondrial membrane potential and inhibiting Akt signaling (31). Likewise, May et al. (2022) demonstrated that dietary supplementation with BRBs increased survival in Apc-deficient mice by reducing intestinal stem cell (ISC) marker expression and tumorigenic potential. Similar effects were observed in human CRC organoids, suggesting that anthocyanins modulate ISC homeostasis to exert chemopreventive effects (37). Moreover, epidemiological evidence has shown a strong inverse association between dietary anthocyanin intake and CRC risk (OR = 0.21; 95% CI: 0.08–0.55) (38).

Anthocyanins from AMA inhibit superoxide dismutase (SOD) activity in Caco-2 cells. When treated with 50, 100, and 200 micrograms per milliliter of anthocyanins, SOD levels progressively decreased from 46.2 units per milligram to 20.0 units per milligram, reducing the cellular capacity to neutralize oxygen-free radicals and intensifying lipid peroxidation and oxidative stress. Moreover, malonic dialdehyde levels, which reflect the extent of lipid peroxidation and indirectly indicate cellular damage, increased significantly. These findings suggest that anthocyanins may inhibit SOD activity, impair the scavenging of oxygen-free radicals, exacerbate oxidative stress and lipid peroxidation, and ultimately induce apoptosis in CRC cells (30).

Four studies assessed the effects of anthocyanins on gut microbiota. Rodriguez et al. (2022) examined the impact of freeze-dried BRB supplementation in a mouse model of colitis-associated colorectal cancer. Supplementation with 5% or 10% (w/w) whole BRB favorably modulated the fecal microbiome, particularly during active colitis, and reduced both colitis severity and tumor burden in mice fed a total WD. BRB intake increased alpha diversity (i.e., species richness, evenness, or diversity within the sample) and significantly altered beta diversity (i.e., the similarity between two or more communities), reflecting broad changes in microbial community structure. Distinct microbial profiles were observed before colitis onset, during inflammation, and throughout tumor development. The intervention led to increased relative abundance of bacterial families such as Lachnospiraceae, Ruminococcaceae, and Rikenellaceae, with variations depending on the basal diet and disease phase. Of particular interest, BRB supplementation enriched Bifidobacterium pseudolongum, a taxon linked to anti-inflammatory and immunomodulatory effects (33).

A related study by Fernández et al. (2018) evaluated the effects of anthocyanin-enriched functional sausages on gut microbiota composition in rats over a 20-week period. Animals were assigned to one of three dietary groups: standard, control sausages, or functional sausages supplemented with 0.1% (w/w) anthocyanins derived from a mixture of dehydrated blackberries and strawberries. Metagenomic analysis revealed that, at the genus level, the only statistically significant difference was found within the Desulfovibrionaceae family, specifically in the relative abundance of Bilophila wadsworthia, a sulfite-reducing bacterium known for producing hydrogen sulfide (H₂S). This species accounted for 7.90% of the total metagenomic content in the control sausage cohort, but was reduced to 4.94% in the functional sausage group. These findings suggest that dietary anthocyanins may influence gut microbiota composition by reducing the relative abundance of potentially pro-inflammatory taxa such as Bilophila wadsworthia, which may contribute to improved intestinal health (32). In a case-control study, Speciani et al., 2022 analyzed circulating bacterial DNA profiles in blood samples from CRC patients and matched controls, alongside dietary flavonoid intake. They found that anthocyanins were negatively associated with operational taxonomic units (OTUs) assigned to Flavobacterium and Legionella, and positively associated with OTUs assigned to the Brevundimonas genus. Additionally, anthocyanidins showed a negative association with the Escherichia–Shigella group and a positive association with OTUs from the Oligoflexales order. The observed associations imply that anthocyanins can modulate circulating bacterial DNA levels, possibly through effects on intestinal permeability (39). On the other hand, anthocyanins-treated ApcMin^/+ mice inoculated with enterotoxigenic Bacteroides fragilis, a model of bacteria-induced inflammatory bowel disease that secretes a metalloprotease enterotoxin, showed a clear dose-dependent reduction in colon tumor counts compared to untreated controls (34).

Several studies have demonstrated that anthocyanin-rich extracts modulate key inflammatory pathways and cytokine expression both in vitro and in vivo. BRB anthocyanins suppress inflammation in CRC models by downregulating SIRT1, which enhances NF-κB/p65 acetylation and reduces the expression of pro-inflammatory targets such as NOX2 and NLRP3. This effect is accompanied by a reduction in reactive oxygen species (ROS) levels (36). Additionally, anthocyanins have been shown to significantly reduce inflammatory markers, including COX-2, IL-6, IL-17, MUC2, MPO, TNF-α, and IFN-γ in CRC cells (Figure 3) (35). Berry anthocyanins have also been shown to modulate immune responses within the tumor microenvironment by inducing lymphoid aggregates and regulating key molecular markers. In adjacent normal tissue, berry anthocyanins reduced the expression of COX-2, meanwhile increasing the expression of IFN-γ, phospho-p38, TLR-4, and PD-L1. In the tumor tissue microenvironment, berry anthocyanins reduced levels of COX-2, TLR-4, and PD-L1, indicative of their chemopreventive modulation of the inflammatory environment in CRC (34).

Across the revised studies, varying concentrations of anthocyanins were administered to CRC cell lines, including Caco-2, SW480, LoVo, HCT 116, and HT-29, as well as to organoids ISO48 and ISO50, with doses ranging from 20 to 3000 μg/mL (Table 2). All studies reported a consistent dose-dependent response, whereby higher anthocyanin concentrations correlated with greater anticancer effects.

The anthocyanin dosages used in both in vivo and human studies are summarized in Table 3. In animal models, anthocyanins were administered either at defined doses based on body weight (mg/kg) or as anthocyanin-enriched diets. Human data, derived from both clinical trials and observational studies, involved dietary supplementation or intake estimation using validated food frequency questionnaires. In all cases, anthocyanin consumption was quantified to evaluate its potential role in the prevention and progression of CRC. Notably, these studies consistently reported lower anthocyanin intake among CRC patients compared to healthy controls, suggesting a potential protective effect.

Among the 16 studies included in this systematic review, six provided clear evidence linking the WD pattern to the development of CRC (13, 33, 40–43).

Andersen et al. (2019) identified significant gene–diet interactions between red and processed meat intake and four polymorphisms (CCAT2 rs6983267, TP53 rs1042522, LPCAT1 rs7737692, and SLC25A20 rs7623023) associated with CRC risk in a Danish cohort. T-allele carriers of CCAT2 rs6983267 had a lower CRC risk compared to GG homozygotes, while variant alleles of TP53 rs1042522 and LPCAT1 rs7737692, as well as the AA genotype of SLC25A20 rs7623023, were linked to increased CRC risk with higher meat intake. These findings suggest that red and processed meats may promote CRC through pathways related to inflammation and fatty acid metabolism (43). Similarly, Feng et al. (2021) confirmed a causal relationship between processed meat consumption and a 23% increased CRC risk, independent of confounders such as sodium intake (41).

Preclinical studies demonstrated that mice fed with WD exhibited aggravated colitis, heightened inflammation and mucosal damage, delayed epithelial repair, and a significantly increased tumor burden compared to controls. These effects were attributed to nutritional deficiencies in the WD, particularly reduced levels of calcium and vitamin D (13). Further supporting this, Rodríguez et al. (2022) showed that WD-fed mice displayed altered gut microbiome composition and elevated tumor multiplicity, with WD exposures modulating key microbial taxa (33). In epidemiological studies, Castelló et al. (2022) observed a positive association between adherence to a WD pattern and CRC risk, particularly during the first 10 years of follow-up. Individuals in the highest quartile of WD adherence had a 53% increased risk of CRC, with the effect being especially pronounced for rectal cancer (42).

Abd Rashid et al. (2023) identified a processed dietary pattern rich in fast foods and confectionery that significantly increased the risk of CRC in a Malaysian population with diverse socioeconomic backgrounds (40). Together, these findings reveal that WD components not only promote local intestinal inflammation and dysbiosis but may also interact with host genetics and micronutrient deficiencies to drive colorectal tumorigenesis.

Emerging evidence highlights the critical role of WD components in the development of CRC, primarily through mechanisms involving chronic intestinal inflammation and gut microbiota dysregulation (13, 33). In a controlled animal study, transcriptomic analysis showed marked upregulation of genes linked to interferon response, inflammation, immunity, and chemokine signaling in mice fed a total WD during active colitis. These alterations, along with activation of B-cell and antigen processing pathways, persisted throughout recovery and paralleled ongoing mucosal injury. These findings suggest that sustained inflammation and colonic dysplasia are key mechanisms by which the total WD promotes colitis-associated colorectal carcinogenesis (13). Furthermore, genetic factors may modulate CRC risk under inflammatory conditions; for example, the TP53 rs1042522 polymorphism was shown to interact with nonsteroidal anti-inflammatory drug use, with GG homozygotes experiencing reduced CRC risk and carriers of the variant C allele showing increased risk (43). Collectively, these studies support the conclusion that WD patterns exacerbate colonic inflammation, which plays a central role in initiating and promoting tumorigenesis in the colon.

In a complementary study, Rodríguez et al. (2022) reported that although BRB supplementation altered gut microbiota composition and enhanced microbial diversity, it did not lead to consistent reductions in colonic inflammation in mice fed with WD. Histopathological analyses revealed persistent mucosal injury and inflammatory cell infiltration across groups, with significantly higher inflammation and mucosal damage scores in total WD-fed mice compared to those on the healthy diet. These findings suggest that the pro-inflammatory effects of the WD may override the potential anti-inflammatory benefits of dietary interventions such as BRB supplementation (33). Collectively, the evidence points towards the existence of distinct mechanistic pathways through which WD patterns and anthocyanin-enriched interventions influence colorectal carcinogenesis (Table 4). Notably, their divergent effects on intestinal inflammation, microbiota composition and oncogenic signaling provide critical insights into the dietary modulation of CRC risk and offer a framework for evaluating the preventive potential of bioactive nutritional compounds.

Although our review focused on studies published before mid-2024, recent research has provided additional insights that further strengthen and expand our understanding of how WD patterns and anthocyanin-rich diets influence CRC. Among CRC survivors in the United States, adherence to a WD pattern has been associated with poorer social functioning (45). Moreover, recent evidence confirms that WD, characterized by high intakes of trans fats and saturated fatty acids, is linked to an increased risk of CRC (46). Red meat consumption may promote CRC progression through the incorporation of N-glycolylneuraminic acid into intestinal epithelial cells, which activates the Wnt/β-catenin signaling pathway independently of immune-mediated mechanisms (47). In addition, the CRC Microbial Dietary Score (CMDS) has been positively associated with consumption of highly processed foods, such as processed meats, energy drinks and snacks, and negatively associated with intake of fiber-rich foods, including fruits, nuts, dark yellow vegetables, and legumes. Elevated CMDS correlated with microbial species enriched in CRC and was linked to a higher risk of CRC, particularly in tumors containing F. nucleatum, pks + E. coli, and enterotoxigenic Bacteroides fragilis (48).

On the other hand, anthocyanin and polyphenol-rich chokeberry and blueberry pomace extracts inhibit proliferation and metastasis in CRC cells by modulating ERK, Akt1, gp130, and STAT3 pathways (49). Similar results were observed for cyanidin 3 O glucoside (Cy3g), a natural anthocyanin, that dose dependently inhibited proliferation, migration, and invasion, while promoting apoptosis in CRC cells. In tumor-bearing mice, Cy3g reduced CRC growth by activating KLF4 and modulating the ERK and p38 signaling pathways (50). In addition, supplementation with 5% or 10% dehydrated calyces of Hibiscus sabdariffa, a significant source of anthocyanins and phenolic compounds, modified gut microbiota composition by increasing butyrate producing bacteria. These dietary interventions also elevated caspase 3 and cMyc expression, indicating potential activation of apoptotic mechanisms (51).

Despite encouraging evidence, the translation of anthocyanins into routine clinical practice remains limited by low oral bioavailability, extensive metabolism, and rapid systemic clearance, resulting in highly variable systemic exposure (52). In addition, substantial variability in anthocyanin content across food sources, processing methods, and formulations complicates standardization and reproducibility in clinical studies. Although bioavailability may be enhanced through advanced delivery systems, such as nanoencapsulation, nanogels, nanoemulsions, liposomal carriers, and chemical modifications, including acylation and co-pigmentation (53), evidence indicates that anthocyanins consumed within whole foods exhibit superior bioavailability and biological activity compared with isolated or purified extracts, likely due to synergistic interactions within the food matrix (54).

This systematic review provides valuable insights to the influence of anthocyanin intake and WD patterns on CRC risk; however, several limitations warrant consideration. Substantial heterogeneity across study designs, intervention durations, and the specific sources of anthocyanins and WD components introduces variability that limits direct comparison and synthesis. Moreover, the predominance of preclinical and observational studies restricts the ability to draw definitive causal inferences or to generalize findings to clinical settings. Additionally, the predefined terminology used in the search strategy, although considered the most relevant, did not include all possible synonyms or variations employed in CRC research, which may have reduced the retrieval sensitivity of the systematic search. Future systematic reviews should perhaps consider incorporating a broader and more comprehensive terminology to ensure the identification of additional relevant studies.

This systematic review highlights the contrasting effects of WD patterns and anthocyanin-rich diets in the development and prevention of CRC. WD, characterized by high intakes of red and processed meats, refined carbohydrates, and saturated fats, is consistently associated with chronic colonic inflammation, disruption of the gut microbial environment, and accelerated tumor progression. In contrast, anthocyanins exert multiple chemopreventive effects, including the reduction of oxidative stress, suppression of proinflammatory cytokine production, inhibition of oncogenic signaling pathways, such as those involving Wnt/β-catenin, mTORC1, and NF-κB, and restoration of intestinal barrier function and microbial diversity. Evidence from in vitro, in vivo, and human observational studies supports the notion of a dose-dependent inverse relationship between anthocyanin intake and CRC risk. Although anthocyanins are not intended to replace standard therapies, they may serve as complementary agents that enhance treatment response and modulate cancer-promoting pathways. These findings support anthocyanin-rich dietary strategies as a practical, biologically relevant, and accessible approach to CRC prevention. Further clinical trials are essential to validate their efficacy, clarify underlying mechanisms, and improve their bioavailability in human populations.