The mainstays of conventional cancer treatment, namely surgery, chemotherapy and radiation therapy, while preserving and prolonging the lives of many, present toleration challenges and often lack desired effectiveness.
Diet has considerable potential to optimise tolerance to conventional cancer therapies. Notably, there is evidence to suggest that patients who undergo conventional treatments without receiving nutritional support have higher complication rates.
Diet can be utilised to support optimal weight, specifically to prevent weight loss during treatment, to support bowel regularity, and to reduce pain such as headaches, arthralgia and mucositis. There are several dietary patterns and specific nutrients associated with improved survival in cancer treatment.
A whole foods plant-based diet
When one looks across at the body of data as a whole, it is evident that a common denominator is a plant-based diet. Fruit, vegetables and certain components of plant foods, such as fibre and polyphenols, have a large body of data supporting a protective effect against cancer. The impact of this general dietary pattern of a plant-based diet has also been studied in specific cancer patient populations.
In women diagnosed with hormone-dependent cancers, such as breast cancer, and treated with chemotherapy, lowered oestrogen levels as evidenced by the presence of hot flashes (HF) is associated with an approximately 25-30% decreased risk for additional breast cancer events.
With this in mind, the oestrogen-lowering effect of a whole foods, vegetable-rich diet is especially relevant to this group of women. Specifically, changes in dietary patterns to either decrease energy from fat or to increase fibre intake can alter the enterohepatic recirculation of oestrogens, leading to lower circulating oestrogen concentrations. A low-fat/high-fibre diet can be expected to reduce serum estradiol by an average of 7.5%. Although this effect is modest, if it persists over years this would have biological significance.
The beneficial effect of fibre has been noted in clinical trials. For instance, women diagnosed with breast cancer who, within 12 months of their diagnosis, consume significant fibre (average consumption of 15.5g/day of insoluble dietary fibre) experience a 49% reduction in the likelihood of having elevated C-reactive protein (CRP) levels compared to those who consumed an average of 5.4g/day. This suggests an anti-inflammatory effect of fibre consumption which, in turn, improves treatment toleration and is associated with improved survival.
Men diagnosed with prostate cancer also benefit from a whole foods dietary pattern. A diet characterised by significant reduction in the consumption of saturated fat, increased consumption of vegetable proteins with accompanying reductions in animal proteins and dairy products has been shown to significantly increase prostate specific antigen (PSA) doubling-time in men with prostate cancer. The slowed PSA doubling-time reflects decreased prostate cancer progression.
Colon cancer development and progression is also influenced by diet. Frequent consumption of red meat, refined carbohydrates, dairy and eggs is associated with an increased risk for developing colorectal cancer compared to infrequent consumption.
There is also a significant inverse relationship between total fibre intake and risk of colorectal cancer. Vegetable fibre appears to be more protective than either fruit or grain fibre. In patients with diagnosed colon cancer, a dietary pattern that emphasises plant foods and minimises animal sources of protein would be expected to exert a beneficial effect on the colon, perhaps influencing progression risk.
Glycaemic load (GL)
High dietary GL is positively correlated with insulin, IGF-1 and insulin resistance. Insulin and IGF-1 are significant drivers of malignant behaviour in many cancer cells, of all cancer types.[10,11]
Insulin and IGF-1 stimulate cellular proliferation in malignant cells via the constitutively “turned on” insulin receptor (IR) and IGF-1 receptors (IGF-1R) which culminate in mTOR activation. Activated mTOR drives proliferation, alters mitochondrial metabolism toward anabolism (aerobic glycolysis) and decreases apoptosis.
Insulin and IGF-1 levels can become elevated from consumption of a high GL diet. A prospective, observational study of 1011 stage III colon cancer patients reported their dietary intake during and for six months after conventional treatment. The median follow-up from the time of completion of adjuvant therapy was 7.3 years. Higher dietary GL was associated with statistically significant worse disease-free, recurrence-free and overall survival. Specifically, patients with stage III colon cancer who were in the highest quintile of dietary GL experienced an adjusted hazard ratio (HR) for disease recurrence of 1.79 compared with those in the lowest quintile. Increased GL was associated with decreased overall survival). These associations were strongest for overweight patients. These data points support the use of a low glycaemic, nutrient-dense diet in people diagnosed with colorectal cancer.
Plant foods and spices concentrate polyphenols, which possess uniquely potent anti-inflammatory and pro-apoptotic effects in damaged and malignant cells. These effects are synergistic with chemotherapy.
Polyphenols both down-regulate inflammatory NFkB and up-regulate the transcription factor Nrf2. Nrf2 is normally sequestered in the cytoplasm as an inactive complex with its cytosolic repressor Keap-1. Polyphenols cause dissociation of Nrf2 from Keap-1. Once released from Keap-1 repression, Nrf2 translocates to nucleus, forms a heterodimer with small Maf protein, and binds to ARE/EpRE sequences located in the promoter region of genes encoding antioxidant and detoxifying enzymes.
This effect is synergistic with chemotherapy in so far as intracellular antioxidants are required to preserve the apoptotic (cell death) cascade initiated by chemotherapy. Additionally, polyphenols directly up-regulate apoptosis, the final step in chemotherapy-induced malignant cell destruction. There are many examples of these pro-apoptotic polyphenols such as trans-resveratrol from grapes, peanuts, berries and red wine, genistein from soy and curcumin from turmeric activate apoptosis in cancer cells.
These effects of polyphenols have been illustrated in several clinical trials. For instance, a parallel-designed, placebo-controlled clinical trial of 120 men and women aged 40-74 years compared the effect of 300mg of an anthocyanin rich drink isolated from bilberries and black currants to placebo over a three week period. Consumption of the proanthocyanin-containing beverage was found to decrease NFkB-controlled pro-inflammatory chemokines and IFN-alpha (an inducer of NFkB activation) by 45% and 40% respectively vs 20% and 15% in the placebo group.
Another trial assessed the impact of 30g of freeze dried vegetables and mixed herbs stirred into hot water and added to the daily diet of five patients with stage I non-small cell lung cancer (NSCLC) in a toxicity study group and six patients with stage III and IV NSCLC in a treatment group for up to 24 months. These patients were matched to 13 patients with stages III and IV NSCLC in the control group. The medicinal vegetable soup included soybean, shiitake mushroom, mung bean, red date, scallion, garlic, lentil bean, leek, hawthorn fruit, onion, ginseng, angelica root, licorice, dandelion root, senegal root, ginger, olive, sesame seed and parsley. All patients were treated with conventional therapies, including radiation, surgery and/or chemotherapy. Those patients eating the vegetable soup had median survival of 15.5 months compared to a median survival time of 4.5 months in the control group. There was no adverse toxicity in the vegetable/herb group.
There is an emerging body of data which supports specific benefits derived from various flavonoids, members of the polyphenol family of compounds. In a controlled trial, 87 patients, 36 with resected colon cancer and 51 patients after polypectomy, were divided into two groups. One group of 31 patients was treated daily with a flavonoid mixture of 20mg apigenin and 20mg epigallocathechin-gallate and compared with a matched control group of 56 patients. Both groups were observed for 3-4 years by surveillance colonoscopy and by questionnaire. Among the 14 patients with resected colon cancer and treated with the flavonoid mixture, there was no cancer recurrence and one adenoma developed. The cancer recurrence rate of the 15 matched untreated controls was 20% (3 of 15) and adenomas evolved in four of those patients (27%). The combined recurrence rate for neoplasia was 7% (1 of 14) in the treated patients and 47% (7 of 15) in the controls.
In a trial of 26 men with newly diagnosed localised prostate cancer, the subjects were randomised to either 30mg lycopene or no supplement prior to radical prostatectomy.
In the lycopene group, at surgery 84% had tumours less than 4mL vs 45% in the control group. Additionally, 73% of the lycopene group and only 18% of the control group had clean margins. Prostate intraepithelial neoplasia was present in 67% of the lycopene group compared to 100% of the control group. Finally, PSA decreased by 18% in the lycopene group versus an increase of 14% in the control group.
A pooled analysis of three large prospective trials – the Shanghai Breast Cancer Survival Study (SBCSS), the Life After Cancer Epidemiology (LACE) Study and the Women’s Healthy Eating & Living (WHEL) Study – collectively representing 9514 breast cancer survivors with a mean follow-up 7.4 years, assessed the impact of soy isoflavone. Consumption of over 10mg isoflavones per day was associated with a 25% reduced risk of recurrence. This inverse association was seen in tamoxifen users, oestrogen receptor negative and oestrogen receptor positive women.
There is ample evidence to support proactive dietary counsel for people undergoing treatment for cancer. A polyphenolic-rich, high-fibre, low glycaemic load plant-based diet is the foundation of such an approach. Diet is impactful on quality of life and survival. Additionally, patients who make dietary changes are proactively engaged in building their own wellness. In this way, diet becomes a tool for health and for patient empowerment in the face of a daunting illness.
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