Large bowel cancer

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Chapter 24 Large bowel cancer

Introduction

Bowel cancer screening

Colorectal cancer (CRC) is one of the most common forms of cancers in the Western world. Lifetime risk to age 75 in the general population is 1:17 for men and 1:26 for women in Australia and is the second leading cause of death.1

Research shows that the risk of developing bowel cancer rises significantly from the age of 50 and accounts for 85% of sporadic cancers.2

Most cancers of the bowel arise from polyps (adenomas) and removal of polyps markedly reduces the subsequent risk of disease.3

Various countries are in the process of introducing national screening programs, and in Australia a population of greater risk are invited to take part in the program.1

The eligible population in Australia is those turning 50, 55 and 65 years of age between January 2008 and 31 December 2010. In the US, screening will commence at a similar age (50).4 People eligible to participate in the program will receive an invitation through the mail to complete a faecal occult blood test (FOBT) and no cost is involved. There is controversy as to which is the best screening method and also which is the best FOBT.2,5,6 In the US, FOBT will also be used.

There is also increasing evidence to support the use of virtual colonoscopy as an initial screening test.7

If the FOBT is positive, the participant will be advised to discuss the result with their doctor who will generally refer them for a colonoscopy.4 Doing an FOBT every 2 years can reduce the risk of dying from bowel cancer by up to one-third.2

High-risk patients such as those with familial adenomatous polyposis and hereditary non-polyposis CRC need to be screened more frequently. As with all other screening tests, there needs to be an emphasis on combining screening with prevention, in particular with CRC where there is considerable research data on prevention.8

Lifestyle and prevention

The importance of prevention has been highlighted by Baker and Wardle, even suggesting that lifestyle changes could prevent more colorectal than screening.8 Key lifestyle and dietary factors for primary prevention are:

• behavioural factors
• exercise
• diet
• weight
• alcohol
• smoking.

Behavioural factors

Personality factors, especially emotional suppression and loss (and a feeling of hopelessness), have been linked to the occurrence and progression of cancer. Hence, as with almost all chronic illness, behavioural factors have been reported to be important in CRC.9, 10

Recently a population-based prospective cohort study from Denmark investigated associations between personality traits and cancer survival.11 This study showed that neuroticism was negatively associated with cancer survival. A further recent study reported that certain personality factors may not be a risk factor for CRC in the Japanese population. However the report concluded that an ambivalent connection and egocentricity may be protective.12

The relationship between personality traits and cancer remains contentious. However, it should also be noted that behavioural factors play a key factor in influencing other risk factors such as disregard for prudent eating and physical activity regimens which may increase the risk for the development of large bowel cancer.

Physical activity/exercise

Regular and vigorous physical exercise has been scientifically established as being a strong preventative factor against cancer with the potential to reduce incidence by 40%.13 With respect to bowel cancer, physical activity can decrease its incidence by 50%, independent of diet and body weight.14

Mind-body medicine

The diagnosis of cancer presents a major and stressful life event that necessitates an adaptive adjustment to sustain quality of life. A fundamental goal is to enhance quality of life while striving to prolong life. Quality of life has been reported to predict survival in patients with advanced large bowel cancer.15

Surveys of patients with cancer repeatedly identify information provision as a major unmet need. Research has shown that the provision of adequate information is related to an increase in psychological wellbeing.16 Effective communication skills ensure that this information is clearly explained and understood.

There is incontrovertible evidence from 3 meta-analysis of the benefits of psychological interventions in patients with cancer. Such interventions improve emotional adjustment (including anxiety and depression, sense of control, self-esteem), functional status (including daily living activities, social and disease-related symptoms (e.g. like nausea. vomiting, pain) and overall quality of life.17, 18, 19

There are wide benefits from relaxation-based therapies in reducing anxiety, treatment-related phobias, conditioned nausea and vomiting and insomnias.13

Both cognitive behavioural therapy (CBT) and supportive expressive therapy are effective in countering existential fears of dying, aloneness, meaninglessness, and unrealistic fears about the processes of treatment.13–16

Nutritional influences

Diet

Excess energy intake/fat and carbohydrates

Execss energy intake has been shown to be consistently associated with bowel cancer.20

Fat intake is closely associated with energy intake, it has been difficult to differentiate between the two, to add to this confusion a meta-analysis found little evidence of any energy-independent effect of either total or saturated fat.21

Several prospective, observational studies have shown that diet is a major factor in the aetiology of large bowel cancer, with high fish consumption highlighted as decreasing CRC risk. A problem with most of the older studies has been that fats, such as those from fish fats which have been shown to be protective in more recent studies, were not differentiated from other fats.22, 23

A recent randomised clinical trial (RCT) objectively investigated the effects of a 6-month intervention with oil-rich or lean fish versus dietary advice only, on apoptosis and mitosis within the colonic crypt. The participants had either colorectal polyps, inactive ulcerative colitis, or no macroscopic signs of disease.24 The results of the trial showed that the total number of mitotic cells per crypt decreased non-significantly in the salmon group and in the cod group compared with the dietary-advice-only group. The study concluded that an increase in the consumption of either oil-rich or lean fish to 2 portions weekly over 6-months did not markedly change apoptotic and mitotic rates in the colonic mucosa. Moreover it should be noted that fish fats consumption may be a lifetime strategy, not just a short-term solution. A recent review unequivocally concludes that intake of fish fats has a favourable effect on lowering cancer risk.25

High consumption of trans-fatty acids is linked to colorectal adenomas.26

There is confusion as to whether carbohydrate intake can influence CRC, but it would be very unlikely that refined carbohydrates were not a risk factor.27, 28

Meat

A meta-analysis of studies on meat and CRC risk showed that it is a risk factor. Much of the risk was associated with processed meat.29

Dietary fibre

An inverse correlation between plant food and intake in cancer risk in 8 of 10 case-controller cohort studies has been published.30

A systematic review of case-control studies found that 12 out of 13 showed a decreased risk of CRC with increased fibre intake.31

A huge and more recent study of 519 978 participants also showed that fibre intake reduced risk.32

Vegetables and fruit

Vegetables and fruit are more consistently protective against CRC than cereals in case-control cohort studies.25 It is unknown whether vegetable or fruit offer most protection. In general, cruciferous vegetables appear to offer special protection.33

It is likely that the non-fibre vegetable components such as phytonutrients, and vitamins and minerals offer special protection.

Resistance starch

Resistance starch includes those carbohydrates that escape digestion in the small intestine.34

Resistance starch produces the highest level of faecal butyrate which is protective against large bowel polyp/cancer formation.35

Weight/body mass index (BMI)

Obesity and high BMI has been shown to have a direct association with bowel cancer risk independent of physical activity.36

Smoking

A huge study of 1 million adults showed strong evidence linking cigarette smoking and CRC adenomatous polyps.37

Alcohol

In general, total alcohol intake is more consistently associated with CRC risks than specific types of alcohol.38

This positive association of alcohol intake and development of CRC is not as strong for wine intake, especially in women, and wine drinking is not related to rectal cancer.33

Nutritional supplements

Micronutrients

Folic acid

The Nurses Health Study of nearly 90 000 nurses showed an inverse relationship between incidence of colon cancer and dietary folate intake.39 A strong association of alcohol intake with CRC cancers and adenomas have been shown to be associated with low folate and methionine.40

Dietary folate can modify the risk of alcohol consumption on breast cancer, and hence it is possible that folate supplementation could also protect for CRC.41

There is controversial evidence indicating that folate supplementation, later in life, may increase the risk of CRC and possibly other cancers.42

Vitamin B6

An inverse association between intake of dietary vitamin B6 and CRC were shown in a longitudinal study especially in women consuming moderate to excess alcohol.43

Another study has confirmed the importance of vitamin B6.44

Vitamin D/calcium

An inverse association has been shown with vitamin D and CRC.45

It is likely that vitamin D is essential for calcium to reduce recurrence of CRC polyps.46

The most important source of vitamin D production is from skin exposure to sunshine. Vitamin D can be obtained from food sources such as fatty fish, eggs, liver, and fortified foods, but it is unlikely that adequate vitamin D concentrations can be obtained from diet alone.

Magnesium/calcium

In the placebo-controlled calcium/polyp prevention study, calcium supplementation only reduced the risk of colorectal adenoma recurrence in subjects with low calcium/magnesium ratios.47 In this study 1000mg calcium was given for a period of 4 years.

Probiotics/prebiotics

Probiotics and prebiotics are likely to be protective, in particular as they greatly influence the internal bowel environment.48

A number of studies demonstrate that probiotics alter bowel microflora and decrease premalignant and malignant lesions in laboratory experiments in animal studies.49, 50

Radiation enteritis is a severe problem in patients receiving irradiation of the abdomen or pelvis in the course of cancer treatment. Experimental studies in animal models and clinical trials of patients with inflammatory bowel disease (IBD) have consistently shown that the use of probiotic organisms may effectively down-modulate the severity of intestinal inflammation by altering the composition and metabolic and functional properties of indigenous flora of the gut.51 Recently a multi-centre randomised study demonstrated that nutritional intervention with the probiotic drink containing L. casei DN-114 001 does not reduce the incidence of radiation-induced diarrhoea as defined by a Common Toxicity Criteria Grade 2 or greater. However, it had a significant effect on stool consistency as measured by the Bristol scale.52 However an earlier study with 490 patients who underwent adjuvant postoperative radiation therapy after surgery for sigmoid, rectal, or cervical cancer and who were assigned to either the high-potency probiotic preparation VSL#3 (one sachet 3 times a day [tid]) or placebo starting from the first day of radiation therapy showed that with a multi-strain preparation it protected cancer patients against the risk of radiation-induced diarrhoea.53

Phytonutrients

There are several naturally occurring compounds on foods of plant origin (vegetables, fruit, cereals and tea) that have strong protective effects against CRC in addition to their protection from their fibre content.54, 55 Of particular interest are the cruciferous vegetables, onion family, leafy vegetables, tomatoes, as well as fruits and cereals containing carotenoids, vitamin C and E.46 Phytonutrients include carotenoids, vitamin C, vitamin E, folate, indoles, allylic sulphides and lycopene.

Selenium

A multi-centre, double-blind, randomised placebo-controlled cancer-prevention trial was designed to investigate if selenium supplementation could decrease skin cancer incidence.56 This trial found a highly significant reduction of CRC when using a daily dose of selenium of 200mcg.

Another study has shown that selenium levels related inversely to the large adenomas, but this has been confirmed in a nested case-controlled study.57, 58

Vitamins E and C

Several dietary antioxidants such as tea polyphenols, curcumin, genistein, resveratrol, lycopene, pomegranate and lupeol can re-stabilise and modulate cellular metabolic function. A case-control study from Melbourne (Australia) found that dietary micronutrients involved in DNA methylation (folate, methionine and vitamins B6 and B12) and some of those with antioxidant properties (selenium and vitamins E and C) may have a role to play in lowering colorectal cancer risk.59

Stone and Papas highlight the difference between alpha-tocopherol and gamma-tocopherol, and that the latter may be more protective.60

Gamma-tocopherol is a major form of vitamin E in Western diets and has found to be an anti-inflammatory agent plus directly inhibits cyclooygenase-2 (COX-2) activity and this may be another way in which it could be protective.61 These authors highlight the important difference between the synthetic dl-alpha-tocopherol acetate and the natural form.

An earlier meta-analysis of 5 prospective nested, case-control studies indicated that high serum levels of alpha-tocopherol were associated with a modest decrease in subsequent incidence of CRC.62 A more recent study, the large Nurses Health Study, found that 300IU/day of supplemented vitamin E mainly protects CRC in men but not in women.63 A population-based control study of patients with rectal cancer from the US showed that vitamin E and lycopene may reduce the risk of rectal cancer.64

More recently, in 4 major trials involving beta-carotene, vitamin C and synthetic alpha- tocopherol vitamin E, or vitamin C and E or beta-carotene, and vitamin C and E, the latter study involved those with familial adenomatous polyposis. All studies showed no benefit.65–68

All of these latter studies supplemented with the synthetic form of alpha-tocopherol, and also did not use gamma-tocopherol.

Fibre supplements

Soluble fibre (which includes oats as well as a maize extract-hi maize) is fermented into fatty acids including butyrate, which is the major energy source of colonocytes. Other fatty acids include propionate, which is taken up by the liver, and acetate, which enters the peripheral circulation.

Butyrate can activate a colonic receptor with cancer-killing potential. It also has an anti-inflammatory effect.69

Herbs

Liquorice

A recent study found that liquorice prevented CRC in mice.70 COX-2 derived PGE2 promotes CRC regression, and both non-selective COX inhibitors (non-steroidal anti-inflammatory drugs [NSAIDs]) and selective COX-2 inhibitors (Celecoxib) reduces the size and numbers of colonic adenomas. However, increased gastrointestinal side-effects of NSAIDs and increased cardiovascular risk of selective COX-2 inhibitors limit their use in chemo-prevention of CRC.

A derivative of liquorice root reduces tumour COX-2 activity, tumour growth, and metastases in mice without the adverse effects associated with NSAIDs and selective COX-2 inhibitors.

The findings of Zhang et. al. suggest that the enzyme inhibition may be a potentially therapeutic option in CRC.71

Conclusion

Lifestyle changes are important for large bowel cancer prevention and management. Lifestyle changes go further than disease-specific concerns and can potentially improve overall health and wellbeing plus significantly reduce the burden of the disease. It is clearly documented in the scientific literature that people whose diets are low in fibre, fruit and vegetables, with high energy and GI intake, and who do not exercise regularly appear to be at an increased risk of developing large bowel cancer.

Clinicians cannot only provide assistance with early detection but may also provide significant input into the prevention of large bowel cancer by helping people with lifestyle factors that have an overall effect of reducing the risks as well as allay unreasonable and perceived fears associated with treatments. Table 24.1 summarises the current evidence for CAM treatments.

Table 24.1 Levels of evidence for lifestyle and complementary medicines/therapies in the management of large bowel cancer

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Clinical tips handout for patients — large bowel cancer

1 Lifestyle advice

Sleep

• Ensure 7–8 hours sleep and regular sleep pattern. Avoid shift work at night as this can be a risk for cancer. (See Chapter 22 for more advice.)

Sunshine

• Eye protection should be worn in the form of sunglasses at all times when exposed to the sun for prolonged periods of time.
• Amount of exposure varies with local climate.
• At least 15 minutes of sunshine needed daily for vitamin D and melatonin production — especially before 10 a.m. and after 3 p.m. when the sun exposure is safest during summer. Much more exposure is required in winter, when supplementation needs to be considered.
• Ensure gradual adequate skin exposure to sun; avoid sunscreen and excess clothing to maximise levels of vitamin D.
• More time in the sun is required for dark skinned people.
• Direct exposure to about 10% of body (hands, arms, face), without sunscreen and not through glass.
• Vitamin D is obtained in the diet from fatty fish, eggs, liver and fortified foods (some milks and margarines); however, it is unlikely that adequate vitamin D concentrations can be obtained from diet alone.

2 Physical activity/exercise

• Exercise is important for cancer prevention and during treatment. (If in treatment discuss appropriate exercise regimens with your doctor.)
• Exercise for 30–60 minutes daily. If exercise is not regular, commence with 5 minutes daily and slowly build up to at least 30 minutes. Outdoor exercise, in nature, fresh air (avoid polluted air) and sunshine is ideal.
• Brisk walking, light jogging, cycling, swimming, stretching, and weight-bearing exercises are all good forms of physical activity/exercise.
• Tai chi, qigong and yoga may be particularly helpful.

3 Mind–body medicine (most helpful)

• Stress management program — for example, six 40 minute sessions for patients to understand the nature of their symptoms, the symptoms’ relationship to stress, and the practice of regular relaxation exercises.
• Regular meditation practice at least 10–20 minutes daily, especially transcendental, mindfulness meditation and autogenic training.
• Anger management may be of help.
• Psychological therapy may help to deal with stressors.

Breathing

• Be aware of breathing from time to time. Notice if tendency to hold breath or over-breathe.
• Snoring and irregular breathing during sleep needs to be reported and further investigated.
• Avoid exposure to polluted air as much as possible.

Rest and stress management

Relaxation is important for a full and lasting recovery.

• Reduce workload and resolve conflicts. Contact family, friends, church or social groups for support. Full-time work can increase breast cancer risk whereas part-time work does not.
• Listening to relaxation music helps.
• Relaxation massage therapy helps.
• Hypnotherapy, biofeedback, cognitive behavioural therapy, and psychotherapy may be of help.

Fun

• It is important to have fun in life.
• Joy can be found even in the simplest of tasks.
• Treat yourself by watching funny movies/videos, comedy, hobbies, dancing, playing with pets and children.
• Creative tasks, such as knitting, can help with distressing thoughts.
Focus on wellness, not just the disease.

4 Environment

• Don’t smoke and avoid smoking environments.
• Avoid environmental pollutants and chemicals — at work and in the home.
• Avoid artificial sweeteners.

5 Dietary changes

• Do not rush your meals; relax before meals; chew your food thoroughly before swallowing as this aids digestion and promotes regular, relaxed eating patterns.
• Aim to lose weight if you or your health practitioner believes you are overweight.
• Eat more fruit (>2/day) and vegetables (>5day); a variety of colours and those that are in season.
• A vegetarian diet high in legumes is particularly helpful (e.g. soy; vegetables; garlic, nuts and fruit); for example, the Mediterranean diet.
• Increase fibre; for example, cooked oats for breakfast, and add psyllium fibre (husks) to your cereal.
• Fresh garlic and other members of the onion family offer protection.
• Cruciferous or Brassica group of vegetables are protective; they include broccoli, cabbage, brussel sprouts, cauliflower and bok choy.
• Eat more nuts, seeds, beans, sprouts (e.g. alfalfa, mung bean, lentils). Try soy 25–30g/day.
• Consume more fish (sardines, tuna, salmon, cod, mackerel) especially deep sea fish.
• Reduce red meat intake (preferably eat lean red meat e.g. lamb, kangaroo) and white meat (e.g. free range organic chicken fillet).
• Consume cold pressed olive oil, 4 teaspoons, and flaxseed oil, 1 tablespoon (uncooked), daily. Use avocado oil.
• Use dark chocolate (25–50g/day) unless not tolerated.
• Eat a variety of wholegrains/cereals (best if not toasted). Cooked traditional rolled oats for breakfast are particularly helpful, as is rice (brown, basmati, Mahatma, Dongara), buckwheat flour, wholegrain organic breads (rye bread, Essene, spelt, Kamut) — when toasting make hot and crisp, not brown, to avoid acrylamide — brown pasta, couscous, millet, amaranth, etc.
• Consume low-fat dairy products, such as low-fat yoghurt, unless there is a dairy intolerance. Soy milk (organic) is an alternative.
• Drink more water, 1–2 litres a day, and teas (especially green tea, chamomile, peppermint and black tea).
• For alternative sweetener try honey (e.g. manuka, yellow box and stringy bark have the lowest GI).
• Avoid sea salt.
• Avoid hydrogenated, saturated fats and trans-fatty acids such as butter, margarines, crispy potato chips, dairy fat (e.g. yellow cheeses and cream), fat in meat and poultry, commercial biscuits, most cakes, pastries and takeaway foods, fast foods, sugar (such as soft drinks, lollies) and processed foods (e.g. white bread, white pasta).
• Avoid coffee.
• Minimise alcohol intake to no more than 1–2 glasses daily; red wine may be best.
• Avoid chemical additives — preservatives, colourings and flavourings.

6 Physical therapies

• Acupuncture may help with pain and naused (including chemotherapy-induced nausea).

7 Supplements

Fish oils

• Indication: may reduce LBC risk, may reduce inflammation and blood stickiness. Can reduce chemotherapy toxicity and normalise immunity.
• Dosage: 4–10g of 1000mg capsules daily as tolerated (e.g. EPA 180/DHA 120mg/1000mg capsule).
• Results: 4–7 days.
• Side-effects: often well tolerated especially if taken with meals. Very mild and rare side-effects (e.g. gastrointestinal upset); allergic reactions (e.g. rash, breathing problems if allergic to seafood); blood thinning effects in very high doses > 10g daily (may need to stop fish oil supplements 2 weeks prior to surgery).
• Contraindications: sensitivity reaction to seafood; drug interactions; caution when taking high doses of fish oils >4g per day together with warfarin (your Doctor will check your INR test).

Vitamins and minerals

Folate

• Indication: can reduce large bowel cancer (LBC) risk and also adenomas.
• Dosage: 0.5–1mg daily.
• Result: probably years.
• Side effects: no toxicity, best to use in combination with vitamin B6 and vitamin B12.
• Contraindications: high doses commenced later in life may increase risk of LBC later in life.

Vitamin B6

Indication:can reduce LBC risk.

• Dosage: best if dosage is no more than 50mg daily.
• Result: probably years.
• Side-effects: none if recommended dose not exceeded.
• Avoid doses exceeding 50mg/day as high doses and prolonged use can cause B6 toxicity such as neuropathy (e.g. nerve shooting pains, numbness).
• Contraindications: generally safe.

Vitamin C

• Indication: can reduce LBC risk; may reduce thrombosis and improve immunity when combined with natural vitamin E and selenium.
• Dosage: 500–1000mg daily.
• Results: combined with natural vitamin E and selenium, can reduce blood stickiness in 1 week.
• Side-effects: with high doses can cause nausea, heartburn, abdominal cramps and diarrhoea.
• Contraindications: can increase iron absorption. Use with caution if glucose-6-phosphate dehydrogenase deficiency.

Natural vitamin E

• Indication: may reduce thrombosis plus improve immunity when combined with vitamin C and selenium.
• Dosage: 200–400IU/day.
• Results: can reduce blood stickiness in 1 week.
• Side-effects: rare, but can cause nausea, vomiting, abdominal pain, heartburn and diarrhoea. Doses below 1500IU/day are very unlikely to result in haemorrhage; rarely causes diarrhoea, flatulence, nausea, heart palpitations.
• Contraindications: use with caution if bleeding disorder or if taking with blood-thinning medication. If using very high dose, reduce dose before surgery.
• Contraindications: pregnancy (insufficient evidence). Can reduce effectiveness of thyroid hormone replacement.

Vitamin D3 (cholecalciferol)

• Indication: low levels are a risk factor for LBC.
• Dosage: safe sunshine exposure of skin is the safest source of vitamin D. Vitamin D3, cholecalciferol 1000IU. Doctors should check blood levels and suggest supplementation if levels are low.

• Adults: 400–1000IU/day for maintenance; 3000–5000IU/day for 1 month then 1000IU/day if vitamin D level below normal. Ensure repeat blood measurement.
• Children at risk: 200–400IU/day under medical supervision.
• Pregnant and lactating women at risk: under medical supervision.

• Results: unknown.
• Side-effects: very high doses can cause vitamin D toxicity; raised calcium levels in the blood. Can increase aluminium and magnesium absorption; prolonged heparin therapy can increase reabsorption and reduce formation of bone and hence more vitamin D and calcium required.
• Contraindications: thiazide diuretics decrease urinary calcium and hence hypercalcaemia possible with vitamin D supplementation.

Magnesium and calcium (best provided together)

• Indication: calcium and magnesium may decrease LBC risk.
• Dosage: magnesium: children, up to 65–120mg daily in divided doses. Adults, 400–800mg daily including pregnant and lactating women.
• Calcium citrate: 800mg/day or calcium carbonate 1000mg/day in adults. Children 30–40mg daily.
• Results: unknown.
• Side-effects: oral magnesium can cause gastrointestinal irritation, nausea, vomiting, and diarrhoea. The dosage varies from person to person. Although rare, toxic levels can cause low blood pressure, thirst, heart arrhythmia, drowsiness and weakness. Calcium can cause gastrointestinal irritation and constipation.
• Contraindications: patients with kidney disease.

Selenium (sodium selenite, organic selenium found in yeast)

• Indication: may help prevent LBC. May reduce thrombosis plus improve immunity when combined with vitamin C and vitamin E.
• Dosage: 50–100mcg/day daily; do not exceed >600mcg/day (health professional supervision required to avoid toxicity).
• Results: uncertain.
• Side-effects: very mild and rare; nausea, vomiting, rash, sensitivity reactions, toxicity in high doses; nail changes, irritability, fatigue.
Contraindications: pregnancy, lactation, children <12 years of age.

Probiotics

• Indications: may help prevent LBC, can improve immunity. May assist in preventing radiation therapy induced diarrhoea.
• Dosage: variable dose before breakfast (multi-strain formula is best). One capsule or 1tsp pf powder twice daily (mixed in water) before meals.
• Results: few days to a few weeks.
• Side-effects: gastrointestinal disturbance can occur.
• Contraindications: true cow’s milk allergy if contained in product.

Prebiotics/fibre

• Indications: may help prevent LBC; prebiotics promote the growth and activity of specific strains of bacteria in the gut and are best given with a probiotic. Inulin and oligofructose usually used.
• Dosage: variable dose.
• Results: few days to a few weeks.
• Side-effects: often well tolerated. Very mild and rare side-effects; transient abdominal discomfort (e.g. bloating; flatulence).
• Contraindications: severely ill and/or immuno-compromised patients. Allergies to any of the food sources from which inulin and oligofructoses are derived.

Inulin is derived from wheat, onions, bananas, leaks, artichokes, asparagus, hot water extraction from chicory root.

Oligofructoses are plant sugars from a wide variety of fruits, vegetables, and cereals.

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