*3.3.1 Mechanism*

This reduction has been attributed to the presence of calcium, and other compounds such as casein, lactose, lactoferrin and butyrate present in these products, which can also increase calcium bioavailability. The role of yogurt in reducing the risk of CRC can be attributed to the presence of calcium and gut microbiome, most especially the bacteria that produces lactic acid (*Streptococcus thermophiles* and

**Figure 3.**

*Mechanisms of dietary fiber consumption and risk of colorectal cancer.*

*Nutrition: A Natural and Promising Option in Colorectal Cancer Intervention DOI: http://dx.doi.org/10.5772/intechopen.106285*

*Lactobacillus bulgaricus*) which bring about the reduction of soluble fecal bile acids, fecal-activated bacterial enzymes, and nitoreductase [3].

Calcium has the ability to bind free fatty acids and unconjugated bile acids, thereby reducing the toxic effects of these compounds on the colon and rectum [3]. Calcium exerts its effect by promoting cell differentiation and apoptosis, inhibiting cell proliferation, preventing colonic K-ras mutations, and inhibiting colorectal carcinogenesis induced by haem. The major limitation to this is the association of diet rich in calcium to prostate cancer [6]. In view of this, care should be taken in consumption of dairy foods, most especially those high in calcium, although there are many other bioactive constituents present in dairy foods which might contribute to its role in reducing CRC risk.

### **3.4 Fish and fish products**

Several meta-analysis studies have reported that high fish intake (majorly fresh fish such as freshwater fish and sea fish) could reduce the risk of CRC [26–29]. Fish is known to contain long chain polyunsaturated fatty acids (PUFAs), majorly the n-3 fatty acids, including eicosapentaenoic and docosahexaenoic acids and are known to inhibit colorectal carcinogenesis [27, 30]. However, care should be taken in the consumption of processed fish such as salted, dried, smoked, and barbequed fish, as there could be an association with increased risk of CRC. This is because, dried/ salted fish contains N-nitrosamines [26, 31], and fish processing at high temperatures, produce heterocyclic amines, which are carcinogenic [30].

### *3.4.1 Mechanism*

Fish is known to be a good source of vitamin D, and vitamin D alters gene expression directly through the vitamin D receptor and induces cell differentiation and apoptosis, thereby inhibiting the initiation and progression of CRC. Fish also contains selenium, which can prevent or repair oxidative DNA damage, alter metabolism of carcinogens and regulate immune response. High intake of n-3 fatty acids reduces both the synthesis of arachidonic acid metabolites (prostaglandin E2 and leukotriene B4) and the expression of nuclear transcription factor κB (NF-Κb) and inducible nitric oxide synthetase (iNOS). All these processes can inhibit colorectal carcinogenesis [26, 29, 31].

### **3.5 Fruits and non-starch vegetables**

High consumption of fruits and non-starchy vegetables have been associated with reduced risk of CRC [4]. This is due to the presence of several phytochemicals with antioxidant, anti-inflammatory, and anti-cancer properties which include vitamins, carotenoids, tocopherols, ascorbic acid, alkaloids, phenolic compounds, and intake of several other nutrients and compounds such as folate. These compounds counteract the effect of ROS by their antioxidant properties, and inhibit cellular damage and carcinogenic insults [32, 33].

### **3.6 Nutraceuticals and phytochemicals**

Nutraceuticals, also known as functional foods, are bioactive compounds that originated from natural sources such as secondary metabolites in plant, dietary

supplements, herbal products from fruits, vegetables and plants, and microorganisms or marine organisms, that are capable of preventing, treating and managing several diseases including CRC prevention and therapy [34, 35]. Phytochemicals, mainly from fruits and vegetables, possess strong antioxidant and anti-proliferative activities, and a combination of these compounds brings about their synergistic effect against several cancers [33].

### *3.6.1 Secondary metabolites in plants (phytochemicals)*

Carotenoids such as α- and β-carotene from carrots; lycopene from grapes, papaya, and tomatoes; halocynthiaxanthin from a marine organism, *Halocynthia roretzi*, and other phytochemicals which include astaxanthin, cryoptoxanthin, xanthophyll, and zeaxanthin metabolites, have significant role as free radical scavengers and ability to induce apoptosis in CRC cells [34, 36, 37].

Polyphenols, classified into flavonoids and non-flavonoids, are group of phytochemicals which are converted by intestinal microbiota to simple phenolic acids, and are absorbed in the small intestine, thereby reducing the risk of CRC [32, 38]. Polyphenols (resveratrol, catechins, epicatechins, epigallocatechin-3 gallate (EGCG), flavanols, flavones, and isoflavones) from various sources including plants (such as green tea, grapes, turmeric, ginger), marine algae, seaweeds, and microorganisms serve as chemopreventive agents and play significant role against colorectal carcinogenesis [34, 39].

Flavonoids are dietary polyphenols that occur naturally in plant and beverages, such as fruits and vegetables, and juices, and have been associated with reduction in CRC risks [40]. Flavonoids are sub-classified into six based on their chemical structure. These include flavonols (including quercetin, myricetin, kaempferol, and isorhamnetin from sources such as tea, onions, apples, citrus, berries, and broccoli), flavones (including apigenin and luteolin from sources such as celery, perilla, lettuce, and peppers), flavanones (including hesperetin and naringenin), flavan-3-ols (including catechin, epicatechin, epigallocatechin, epicatechin-3-gallate, epigallocatechin-3-gallate from sources such as apples, cocoa, grapes, green tea, and red wine,), anthocyanins (including cyanidin, delphinidin, malvidin, pelargonidin, petunidin, peonidin from sources such as grapes, black currants, eggplant and radishes), and isoflavones (including genistein and daidzein from soy products). These compounds could prevent and reduce the risk of CRC [34, 38].

Apart from the chemopreventive role of these compounds against CRC, there are little or no side effects as compared to other CRC treatment options such as surgery, chemotherapy, and radiation.

### *3.6.2 Dietary supplements*

Dietary supplements such as omega-3 fatty acids, vitamins (vitamin D, folate, and vitamin B complex), eugenol from honey, balm, cinnamon, clove oil, citrus, and Flos, have been reported to reduce the risk of CRC [34, 41].

### *3.6.3 Herbal products*

Herbs and herb products have been used as a single or combination preventive or therapeutic measures for CRC. Several medicinal plants (either as extracts, juices, or diet fortified) have been studied using different experimental models. These include *Nutrition: A Natural and Promising Option in Colorectal Cancer Intervention DOI: http://dx.doi.org/10.5772/intechopen.106285*

the use of *Crassocephalum rubens* fortified diet [42], Indian spice saffron (*Crocus sativus*), *Triticum aestivum* [43], *Camellia sinensis* [44], Chinese herbal medicines [45], and their effect against initiation and progression of CRC. These products have been reported not only to have the potential to reduce the risk of CRC but also capable of reducing the adverse reactions associated with the use of chemotherapy [45]. The preventive and therapeutic potential of these herbs, and their mechanisms of reduction in the risk of CRC could be linked to the several active compounds inherent in them [46].

### *3.6.4 Marine nutraceuticals*

Bioactive compounds from marine organisms including acetylapoaranotin (isolated from marine *Aspergillus sp*), astaxanthin (from crab, marine animals, and *Haematococcus pluvialis*), and siphonaxanthin (from a marine green algae *Codium fragile*) have been of interest as therapeutic intervention for CRC [34], via different mechanisms.

### **3.7 Effect of diet on colorectal cancer patients**

A hospital-based case–control study among Chinese populations, conducted in Hong Kong, revealed that current, regular, and heavy alcohol drinkers, and cigarette smokers increased risk of CRC, and avoidance of these for a long time reversed the risk [47]. A large prospective cohort study where patients were screened showed a reduction in the risk of adenoma in patients taking dietary fiber (most especially from cereal and fruit [48]. Also, in a theory-driven behavioral dietary intervention program conducted on Chinese CRC patients, improvement in diet rich in refined grain and high fibre intake, and reduction in red and processed meat was noted with no dietary deficiency and/or dietary-related anemia, which could be as a result of other sources of protein (poultry, seafood and tofu). This improvement in dietary intervention was linked to awareness on the role of diet in CRC prevention and treatment, thereby resulting in increased chances of patients' survival [49].

In a large British cohort (UK Biobank study), there was a lower risk of CRC among low meat-eaters (those that consumed processed/red meat or poultry in less than 5 times a week) when compared with the regular meat-eaters (those that consumed processed/red meat or poultry more than 5 times a week) [50]. This confirms that high risk of CRC is associated with high and regular diet of processed/red meat. In another large-scale cohort studies (UK Biobank), there was an association between high consumption of processed meat and increased risk of mortality in patients with inflammatory bowel disease, leading to high CRC risk [51, 52].

Among CRC patients in China, it was reported that low intake of poultry, seafood, processed/unprocessed red meat, could prevent high risk of CRC. However, no general agreement on high intake of white meat (fish and poultry) in reducing the risk of CRC, as contrasting results have been reported [53]. In a UK Biobank study, consumption of red/processed meat, below the UK recommended daily intake (not more than 90g of red and processed meat a day) is suggested, as participants consuming an average of 76g per day was associated with increased risk of CRC [54].

In the European prospective investigation into cancer and nutrition (EPIC) cohort study, no association was noted between pre-diagnostic intake of red meat or fibre and CRC survival after diagnosis, However, it was suggested that poultry intake can reduce mortality among female CRC survivors, and increased CRC-specific mortality risk with intake of processed meat. This is because dietary intake before diagnosis is assumed to predict post-diagnostic data, therefore, post-diagnostic dietary research was suggested to confirm the association [55].

There are limited clinical trials evaluating the post-surgery role of diet in CRC patients. Although, studies have shown that diet rich in red/processed meat, refined grains, sweets, and high alcohol consumption were associated with increased recurrence rates of CRC, while increased coffee consumption, dietary fiber, and vegetables, mainly light and low-fat foods, were associated with decreased CRC mortality rate [8, 56]. Also, the alternate healthy eating index-2010 (high intake of whole grains, fruits, vegetables, legumes, nuts, and long chain omega-3 fatty acids, and low intake of salt, saturated fat and red/processed meat) and moderate consumption of alcohol and lower consumption of sugar sweetened beverages and juices were associated with reduced risk of CRC mortality among women [57].

In general, more studies are suggested to investigate the role of nutrition on CRC survival (post-diagnosis), as most dietary data is currently centered on CRC prevention.
