Phytonutrients and their potential role in cancer prevention in the context of integrative oncology

Emerging evidence on the therapeutic power of plant foods

 

Cancer and the many risk factors.

Cancer is a complex disease with multifactorial triggers and multiple therapeutic pathways. It is precisely this complexity which has led to the emergence of greater individualisation in cancer prevention and cancer support, and the need for more integrated treatments to recognise individual diversity. Nutrition and lifestyle recommendations are steadily becoming part of the patient protocol with greater consideration given to the role they play alongside traditional treatments.

 

Cancer is the leading cause of death in the UK (1) and current modelling predicts that by 2038-40, more than half a million people will be diagnosed with cancer each year across the UK (2). Much of this is ascribed to a growing and ageing population; however, prevention is a critical part of this projection. According to some epidemiological calculations, approximately four in ten cases of cancer are attributable to known risk factors including diet. Generic nutrition recommendations include reducing consumption of sugars, alcohol, and processed meats, and increasing consumption of high fibre foods (3). Body weight is another risk factor with excess body weight directly associated with the risk of several cancers (4), so supporting weight loss and maintenance of a healthy body weight is another preventative strategy. These two risk factors alone highlight the importance of nutrition. Furthermore, nutrition protocols can be integrated into cancer support at every stage of the patient journey from the moment a diagnosis is received, during treatment and recovery, and as prevention of future cancer reoccurrence.

 

Nutrition as part of a modern integrated approach to cancer

Cancer was historically viewed as a proliferative ‘genetic’ disease (5,6). In this model, the principal focus was given to the multistep process of tumorigenesis in humans and the genetic alterations that occurred at each step. Newer perspectives have shifted the focus to dysregulated metabolism and common metabolic alterations across cancers and cancer subtypes (7). Metabolic hallmarks of cancer are shaping new therapeutic protocols and paving the way for more detailed nutritional approaches to target inflammation and alterations in things such as glucose, glutamine, and fatty acid metabolism.

 

This focus goes hand in hand with patients seeking to make informed decisions regarding their dietary choices. This often begins at the moment of diagnosis when there is high motivation to seek information about diet, nutrition, physical activity, dietary supplement use, and broader complementary therapies. For example, better overall diet quality is associated with improved survival rates in breast and colorectal cancer patients; and adherence to the Mediterranean diet is associated with lower risk of mortality in colorectal and prostate cancer survivors (8,9).

 

Identifying the exact components of a ‘healthy diet’ that contribute to better cancer outcomes is an area of research which is still emerging. The boom of research into nutraceuticals – broadly defined as any product derived from food sources with extra health benefits in addition to the basic nutritional value found in foods – has improved our understanding of nutrients and dietary components and how they influence epigenetic phenomena (10). Natural bioactive extracts in plant foods are reported to contribute to nutraceutical support in anticancer treatment: inhibition of cell proliferation, antioxidant activities, and anti-inflammatory activities (11). Nutraceuticals can also offer non-toxic, dosage friendly, safe and economical support alongside primary cancer management (12). In this article we specifically explore the potential role of phytonutrients in cancer prevention.

 

Phytonutrients – what are they?

Phytonutrients is the collective name given to active compounds in plant foods that exert a range of health benefits which may be beneficial in preventing chronic disease, including cancer. Plants produce thousands of natural chemicals as an adaptive response to maintain an evolutionary advantage in reaction to their environments. These chemicals protect plants from germs, fungi, bugs, and other threats and these same protective benefits appear to transfer into human health when we consume diets rich in colourful plant foods. Phytonutrients have been shown to reduce inflammation (13), protect against oxidative stress and cellular damage (14), and support detoxification processes (15), all of which have a role to play in chemoprevention – categorised here as the use of natural or biological agents to prevent, suppress or to reverse the initial phases of cancerous activity in cells (16).

 

Phytonutrients are not considered essential to life like other key nutrient groups: carbohydrates, fat, protein, vitamins, and minerals, and yet, with over 25,000 known phytonutrient compounds available in plant foods, we may not yet know the full extent of their potential health benefits. Within the compounds that have been studied, there are six important phytonutrient groups which this article will look at in more detail:

 

• Carotenoids – found in yellow, orange, and red coloured fruits and vegetables.
• Ellagic acid – a polyphenol found in a number of berries and other plant foods.
• Flavonoids – found in a broader range of foods including citrus fruits and green tea.
• Resveratrol – found predominantly in grapes.
• Glucosinolates – found in cruciferous vegetables, broccoli, sprouts, cabbage, and kale.
• Phytoestrogens – found in soy, legumes, and certain seeds.

 

Carotenoids

There are more than 600 carotenoids contained in orange and red plant foods such as pumpkins, carrots, parsnips, corn, tomatoes, bell peppers and more. Carotenoids are fat-soluble compounds, meaning they are best absorbed with fat. Carotenoids may use a variety of pathways for their anti-cancer activity; however, the induction of apoptosis (cell death) is considered the most common (17). Lycopene, which is found in tomatoes, has several anti-cancer mechanisms including inhibiting the growth of prostate and breast cancer cells by inhibiting NF-κB signalling whilst also increasing levels of reactive oxygen species (18). A systematic review and meta-analysis of randomized controlled trials on the effect of lycopene supplementation on prostate specific antigen (PSA) however, found tomato extracts or lycopene treatment yielded no significant effect on PSA levels compared to the control group, highlighting the need for more consistent clinical trials, with larger sample sizes (19) to better understand effects. A meta-analysis of retinol and carotenoids and in association with colorectal cancer (CC) found that high intakes of beta-carotene may lower risk in men, and retinol may reduce risk in females but increase CRC risk in males (20).

Lutein and zeaxanthin are two other carotenoids known to exert anti-inflammatory and antioxidant properties which may lower the risk of certain cancers and inhibit the proliferation of breast and lung cancer cells (21,22).

 

Ellagic Acid

Ellagic acid, is one of many polyphenols found in fruits and vegetables including blackberries, raspberries, strawberries, cranberries, walnuts, pecans, pomegranates, and others, and which exerts strong antioxidant effects (23). A 2022 review found ellagic acid modulates the expression of various genes incorporated in the cancer-related process of apoptosis and proliferation, inflammation related-gens, and oxidative-related genes (24). The Mediterranean diet is one diet known to provide many plant-foods rich in polyphenols, including ellagic acid, and may potentially reduce cancer development risk as polyphenols show anti-proliferative, pro-apoptotic, anti-inflammatory, antioxidant, anti-migration, anti-angiogenic, anti-metastatic, and autophagy stimulator effects (25). Ellagic acid may increase tumours’ sensitivity to chemotherapy and radiation, thereby enhancing the effectiveness of these cancer treatments (26).

 

Flavonoids

Flavonoids are a group of plant metabolites and are the most abundant antioxidants in the human diet found in fruits, vegetables, grains, bark, roots, stems, flowers, tea, and wine with high levels in apples, berries, cherries, plums, broad beans, olives, onions, shallot, and spinach. They act mainly by scavenging reactive species which may damage healthy cells and, in this way, exert protection over cells. A 2023 review found that ten different flavonoids were identified as having a potential role in cancer treatment mainly through promoting cancer cell death (27). There is also increasing evidence that flavonoids exert anticarcinogenic effects by reshaping gut microbiota in a complex and bidirectional relationship between gut microbiota and carcinogenesis (28). Flavonoids typically have a low absorption rate, and the breakdown of flavonoids is commonly mediated by gut microbiota which may explain this effect. Flavonoids seem to have hormone-like and anti-hormone properties so that the consumption of flavonoids may have potential effects on hormone-related cancers (HRCs). One systematic review and meta-analysis of observational studies suggests that intake of total flavonoids, flavonols, flavones, flavanones, flavan-3-ols and isoflavones could be associated with a lower or higher risk of HRCs. However it cautions that menopausal status may be an important consideration for women when considering breast cancer risk (29).

 

One specific flavonoid, Epigallocatechin-3-gallate (EGCG), the main compound in green tea, initiates cell death in several cancers (30), decreases prostate-specific-antigen levels in prostate cancer, and could be a possible complementary method for relieving acute radiation-induced diarrhoea (31).

 

Resveratrol

Resveratrol is a polyphenol compound found in certain plants and in red wine. Major dietary sources also include grapes, wine, peanuts, and soy. Many studies have found that polyphenols including resveratrol improve metabolic disorders through direct or indirect pathways which protect the liver from liver cancer (32). The wider anticancer potential of resveratrol is recognised in numerous in-vivo and in-vitro studies where it has been shown to activate tumour suppressor genes, suppress cell proliferation, induce apoptosis, inhibit angiogenesis and modulate several other cell signalling molecules (33). Resveratrol also has antioxidant capacities associated with its ability to remove reactive oxygen species (34) and increase SOD activity in prostate cancer, liver cancer and breast cancer cells (35) thus reducing cellular damage to healthy cells.

 

Glucosinolates

Glucosinolates are natural components found in many pungent smelling and tasting plants in the Brassicaceae family, including broccoli, cabbage, cauliflower, rapeseed, mustard, rocket, wasabi, watercress and horseradish. Current research suggests that glucosinolates (and isothiocyanates) act via several mechanisms, ultimately exhibiting anti-inflammatory, antioxidant and chemo-protective effects including inhibition of cell proliferation and angiogenesis, suppression of gene expression in the progression of prostate cancer (36), decreased breast cancer progression (37), reduced cell growth in liver and colon cancers(38). A meta-analysis of allium vegetables, such as garlic, onion, and leeks, which are characterised by their pungent smell and high content of organosulfur compounds, found that consumption could reduce the risk of non-digestive tract cancer (39).

 

Phytoestrogens

A phytoestrogen is a plant-derived xenoestrogen which mimics effects similar to those of the hormone oestrogen. Foods containing phytoestrogens include soy beans, tofu, tempeh, soy beverages, linseed (flax), sesame seeds, wheat, berries, oats, barley, dried beans, lentils, rice, alfalfa, mung beans, apples, carrots, wheat germ, rice bran, and soy linseed bread. There is much research on phytoestrogens during menopause as a natural alternative to hormone treatments and reducer of risk factors of hormonal breast cancers. A 2022 meta-analysis showed consumption of soy isoflavones may reduce the risk of breast cancer in pre-menopausal and post-menopausal women (40). Meanwhile in men, phytoestrogens may influence prostrate cancer progression. A meta-analysis of Japanese men, with high compared circulating isoflavones (genistein, daidzein, equol) concentrations, had a lower risk of prostate cancer (41) than European mean with lower circulating isoflavones. A number of pre-clinical and clinical trials are being carried out on genistein, an isoflavone compound found abundantly in soy and soy-based products, to study its effects in combination with other chemotherapeutic agents as possible treatment of prostate, bone, colorectal, glioma, breast, and bladder cancers (42).

 

Phytonutrients as a core strategy in cancer nutrition

An individual’s nutrient status at every stage of the cancer journey can inform outcomes and play an important part in the body’s response to treatments and side effects of treatments. Optimising the diet to prepare for treatment, or in response to treatment-related symptoms, or to support recovery, and prevent reoccurrence allows for multiple nutritional touch points. Phytonutrients can play a part in each of these phases by helping to reduce inflammation, exert antioxidant activities, and deliver many other anti-cancer mechanisms as highlighted above.

 

There are over 25,00 phytonutrient compounds and these plant-derived bioactive metabolites have acquired an imperative function in human diet and nutrition. This article merely scratches the surface and seeks to highlight how each, and every nutrient has a role to play in health, wellbeing and disease prevention. In addition to the phytonutrient groups highlighted above there are many other compounds that have been studied in relation to cancer. Not all exert beneficial activities. For example, high consumption of capsaicin (contained in chillis) may increase the risk of certain gastric cancers (43). It is therefore always important to consider personalising nutritional recommendations to ensure the safety and wellbeing of individuals.

 

What we can see in very generic terms is that as modern diets have become increasingly ultra-processed and nutrient poor, the rise in chronic disease, including cancer, has grown. This may be in-part fuelled by an increase in obesity, widespread inflammation and a cascade of metabolic dysregulation leading to the perfect storm of conditions leading to cancer. Diet is one of the leading modifiable risk factors for cancer and cancer prevention, and including plenty of plant foods and fibre forms part of the World Cancer Fund recommendations below alongside limiting red and processed meats, sugar and sugar sweetened beverages, and alcohol (Figure 1).

 

There is considerable overlap between sources of phytonutrients in plant foods, making it difficult for individuals to know which foods to include more or less of. General recommendations are to include a wide variety of colourful plant foods in your daily diet to ensure an optimal intake of all phytonutrient groups. The BANT Wellness Solution provides general advice to support healthy dietary and lifestyle choices where personalised advice is not possible, with the recommendation to fill half your plate with plant foods. For more personalised guidelines it is always advisable to seek a qualified nutrition practitioner.

Nutrition Practitioners

Integrative oncology is an approach to cancer care that uses complementary therapies to support the whole patient: mind, body, and spirit, with dedicated focus on nutrition. The British Society for Integrative Oncology (BSIO) is the leading professional organisation for integrative oncology in the UK whose goal is to promote the integration of conventional, nutritional, lifestyle and complementary medicine to improve the lives of people affected by cancer.

BANT nutrition practitioners who have undertaken additional training in cancer nutrition combine a network approach to complex systems, incorporating the latest science from genetic, epigenetic, diet and nutrition research to inform individualised recommendations and support individuals. Find a Registered Nutritional Therapy Practitioner here and visit BANT for more resources on making healthier food choices with our free Food for your Health toolbox of food guides, infographics and fact sheets.

Author: Claire Sambolino MSc, BANT Communications Manager & Registered Nutritional Therapy Practitioner rCNHC

 

 

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