Colorectal Cancer

Integrative
Care

Guidelines

Examples

Integrative
Therapies

Terrain

Risk

Surgery

Quick Reference

Updated February 2021: Open a 2-page quick reference summary of the therapies best supported by evidence for use with colorectal cancer:

Key Points

Early detection, allowing for early treatment, is very important with colorectal cancer.
Eating Well and Moving More, two of our 7 Healing Practices, pack a powerful one-two punch in potentially improving treatment outcomes, enhancing quality of life and/or reducing risk of recurrence in colorectal cancer.
Conventional treatments are readily available. Complementary therapies can be useful to enhance conventional treatment effects, improve quality of life and possibly even extend life for those with colorectal cancer.
An observational study and a case study provide examples of integrative approaches. See Examples of Integrative Approaches.
A number of natural products; off-label, overlooked, or novel cancer approaches (which we call ONCAs); and other therapies show benefits in four domains:
- Treating the cancer
- Managing side effects and promoting wellness
- Reducing risk of both cancer onset and recurrence
- Optimizing your body terrain
The microbes in your gut influence colorectal cancer development and might influence the success of treatment.
Choices for pain relief during and after surgery can impact treatment outcomes and risk of recurrence.

Authors

Laura Pole, RN, MSN, OCNS, BCCT Senior Researcher

Nancy Hepp, MS, BCCT Project Manager

Reviewer

Barry D. Elson, MD, BCCT Advisor

Last updated September 3, 2021.

Colorectal cancer is a term used to include several types of cancers of the colon and/or rectum. Common types of colorectal cancers:¹

Adenocarcinomas of the colon and rectum
Gastrointestinal carcinoid tumors
Primary colorectal lymphomas
Gastrointestinal stromal tumors
Leiomyosarcomas
Melanomas of the colon or rectum

The evidence presented here for screening, diagnosis, treatment and reducing risk relates to carcinomas, of which the great majority are adenocarcinomas. The other cancer types are much less common, and behave quite differently.

Colorectal cancer begins when healthy cells in the lining of the colon or rectum change and grow out of control. These cells form a mass called a tumor, which can be cancerous or benign. A cancerous tumor is malignant, meaning it can grow and spread to other parts of the body. A benign tumor can grow but will not spread. These changes usually take years to develop.²

Colorectal Cancer: Signs, Symptoms and Screening

Signs and symptoms from the American Cancer Society:³

A change in bowel habits—such as diarrhea, constipation or narrowing of the stool—that lasts for more than a few days
A feeling that you need to have a bowel movement that's not relieved by having one
Rectal bleeding with bright red blood
Blood in the stool, which might make the stool look dark brown or black
Cramping or abdominal (belly) pain
Weakness and fatigue
Unintended weight loss

Integrative Care in Colorectal Cancer

Before investigating integrative care in colorectal cancer, we recommend reviewing integrative cancer care in general.

Our goal is to help you live as well as you can for as long as you can. We provide information about using an optimal integrative combination of conventional and complementary therapies and approaches. In this handbook, we present a wide range of complementary therapies that have been studied for their effectiveness in colorectal cancer.

Healing and Curing

Many of the integrative approaches in this handbook promote healing, which is not the same as curing. Healing is an inner process through which a person becomes whole. Healing can take place at physical, emotional, mental and spiritual levels. An example of physical healing is when a surgical incision heals.

Integrative Approaches and Surgery

Surgery may be part of the recommended treatment for this cancer type. We provide helpful information about how integrative approaches can coordinate with surgery below in the section titled Surgery and Colorectal Cancer.

We recommend these resources to introduce you to conventional therapies and the science behind them:

National Cancer Institute:
Cancer.net: Colorectal Cancer

National Comprehensive Cancer Network:
- Professional Guidelines (Login required):
  - Colon Cancer
  - Rectal Cancer
- Guidelines for Patients:
  - Colon Cancer
  - Rectal Cancer

American Society of Clinical Oncology: Gastrointestinal Cancer

Screening Guidelines

For Health Professionals: Surveillance Schedule

Recommended schedule of surveillance for colon and rectal cancer (AJCC stage I (at increased risk for recurrence^a), stage II, stage III, and stage IV (when isolated metastases are resected for cure)¹⁰

Colon

Rectum^b

Notes and Definitions

Clinical Guidelines Committee of the American College of Physicians: Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults: A Guidance Statement From the American College of Physicians (2019)
British Medical Journal: Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline (2019)
The American College of Gastroenterology: ACG Clinical Guidelines: Colorectal Cancer Screening 2021

Guidelines following Curative Treatment

Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons: Practice guideline for the surveillance of patients after curative treatment of colon and rectal cancer

Other Professional Recommendations

The US Preventive Services Task Force recommends initiating low-dose (81 mg) aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer in adults aged 50 to 59 years who have a 10 percent or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years.¹¹ Use is not recommended for others, as risks from taking aspirin may outweigh benefits. Even those not at risk may experience catastrophic gastrointestinal bleeding.

Examples of Integrative Approaches

Bastyr Integrative Oncology Research Center (BIORC)

Life Over Cancer System

The Block Center for Integrative Cancer Treatment (BCICT), founded by integrative oncologist and BCCT advisor Keith Block, MD, offers a comprehensive cancer treatment program combining conventional treatments—often delivered in novel ways, such as according to circadian rhythms—along with nutrition and supplementation, fitness and mind-spirit instruction. The program is highly individualized and provides care to people with any kind of cancer.

Dr. Keith Block reported a case study of a 49-year-old man with colorectal cancer diagnosed in December 2002. Three years post diagnosis, after two surgeries and 12 chemotherapy cycles, he was in remission. In January 2006, he was diagnosed with stage 4 metastases.

Dr. Block prescribed an individualized program to enhance treatment tolerability, reduce treatment toxicity and boost treatment effectiveness through molecular profile testing. The Life Over Cancer program includes these therapies:

Therapeutic nutrition to boost stamina, counter fatigue and reduce chemotherapy side effects
Mind-spirit interventions to reduce stress
Exercise to build strength and fitness
Chronomodulated chemotherapy via a portable pump which deliversboth chemotherapy drugs and intravenous supplemental nutrients

The patient's outcome:

He was able to stay active because of the portable pump.
His scans improved.
He reported no troubling side effects, and he tolerated the chemotherapy so well he did not need to reduce the dose.
After seven chronotherapy sessions (five fewer than would have been used conventionally), he showed no evidence of disease (NED).
As of the writing in 2009, seven years after his original diagnosis and three years after diagnosis of stage 4 metastases, the patient was in complete remission and back at work.
For comparison, in the USA, colon cancer has a five-year life relative survival rate of 63 percent across all stages, and a 14 percent rate for distant spread (metastases).¹⁴

This approach is discussed in detail in a 2018 article, including Block’s use of three spheres of intervention: improving lifestyle, regulating biology, and enhancing treatment.¹⁵

Integrative Programs, Protocols and Medical Systems

For more information about programs and protocols, see our Integrative Programs and Protocols page.

Traditional Medicine Therapies

Throughout this summary, you will find examples of therapies used by, and in many cases created by, traditional medical systems. Foods and herbs such as medicinal mushrooms, soy and curcumin are part of traditional systems.

Programs and protocols
- Alschuler & Gazella complementary approaches¹⁶
- Block program¹⁷
- Cohen & Jefferies Mix of Six anticancer practices¹⁸
- Lemole, Mehta & McKee colorectal cancer protocol¹⁹
- McKinney colorectal cancer protocol²⁰
- Parmar & Kazcor treatment plans²¹
Traditional systems
- Ayurveda
- Traditional Chinese medicine²²
- Traditional Korean medicine²³

Integrative Therapies in Colorectal Cancer

7 Healing Practices: The Foundation

Top 5 Lifestyle Interventions following Colorectal Cancer Treatment

The authors of After Cancer Care: The Definitive Self-Care Guide to Getting and Staying Well for Patients with Cancer recommend these lifestyle interventions,²⁴ which we’ve matched to the 7 Healing Practices:

Any of the 7 Healing Practices are a good beginning. Eating Well and Moving More pack a powerful one-two punch in potentially improving treatment outcomes, enhancing quality of life and/or reducing risk of recurrence in colorectal cancer. Moreover, evidence shows that Managing Stress, Sleeping Well, Creating a Healing Environment, Sharing Love and Support and Exploring What Matters Now can help patients and survivors. Ultimately, let your intuition guide you in choosing where to start with these healing practices.

Bundling Practices Leads to Better Results

People who followed the World Cancer Research Fund/American Institute of Cancer Research recommendations on diet, physical activity, and body fatness prior to a diagnosis of colorectal cancer showed better overall and cancer-specific survival after diagnosis. The more recommendations that were followed, the better the outcomes.²⁵

A 2018 study of almost 1000 colorectal cancer survivors found a 42 percent reduction in death at five years for those who followed the American Cancer Society nutrition and physical activity guidelines most closely, compared to those who followed them least.²⁶

Eating Well

Treating the Cancer

Ask for Guidance

A small study of colorectal cancer survivors in the United Kingdom found that most—more than 2/3—reported receiving no nutritional advice from their doctors and care teams.²⁷ We have no reason to believe the situation is much better anywhere else.

If your team doesn't provide guidance, ask your doctor for a referral to a dietician or nutritionist who specializes in counseling cancer patients and survivors. Even better, seek out an integrative healthcare provider (medical doctor, ostopathic doctor, naturopath, nurse or physician assistant who practices an integrative approach) if you'd like specific guidance about what to eat to improve your outcomes and manage side effects.

Some food choices are associated with better or worse survival:

Higher Survival	Lower Survival
Plant-rich, low-carbohydrate diet in patients with nonmetastatic colorectal cancer²⁸ Diet rich in omega-3 fatty acids²⁹	High dietary insulin load³⁰ Red and processed meat^a³¹

The association is for colon cancer only; no association was found between processed meat intake and overall survival or disease-free survival for rectal cancer.³²

Flax seeds, garlic, green tea and mushrooms and are among the plant foods most commonly used by oncology naturopaths for colorectal cancer.³³

An observational study of patients with stage 3 colon cancer treated with surgery and adjuvant chemotherapy found a link between eating two or more weekly servings of tree nuts and improved disease-free survival and overall survival compared to no nut consumption.³⁴

The ability of foods to influence inflammation may also impact survival. A diet with more anti-inflammatory potential improved overall survival among postmenopausal women diagnosed with colorectal cancer.³⁵ Foods and food components with anti-inflammatory properties:

Managing Side Effects and Promoting Wellness

Higher intake of dietary magnesium is associated with less prevalent and less severe chemotherapy-induced peripheral neuropathy in colorectal cancer patients.³⁶ Foods high in magnesium include these:³⁷

Show list

The Cancer.Net Editorial Board of the American Society of Clinical Oncology recommends a balanced diet that includes specific nutrients such as B vitamins (including B₁ and B₁₂, folic acid) and antioxidants (see Antioxidants and Cancer Outcomes below) to reduce pain from peripheral neuropathy. They also recommend reducing alcohol consumption.³⁸

These foods are among those rich in B vitamins:³⁹

Show list

Reducing Risk

Western dietary patterns—such as eating large amounts of processed meats and refined grains and low quantities of vegetables and fruits—has been associated with higher risk of tumor recurrence and mortality in colorectal cancer.⁴⁰ More than 52,000 new colorectal cancer cases in the United States in 2015 were estimated to be associated with suboptimal diet among US adults.⁴¹ The American Institute for Cancer Research recommends a plant-based diet with a variety of fruits, vegetables, beans and whole grains to lower risk.⁴²

As mentioned above, the Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons recommends a balanced diet after curative treatment of colon and rectal cancer.⁴³ One such balanced diet—the Mediterranean diet, and specifically its components olive oil, red wine, and tomatoes—is associated with clinically reduced cancer initiation and progression.⁴⁴

Strong evidence shows these associations between food choices and risk of colorectal cancer or recurrence:

Lower Risk	Higher Risk
From many sources⁴⁵ Whole-grain foods Dietary fiber, found in whole grains, many fruits and vegetables, and legumes such as black beans, chickpeas or lentils^a Dairy foods, such as milk and plain yogurt Foods rich in marine omega-3 fatty acids, such as fish and fish oils^b Foods high in calcium, such as dairy foods and dark green leafy vegetables	From many sources⁴⁶ Processed meat (preserved by curing, salting, smoking, drying or canning) Red meat Alcohol

Lower Risk

Higher Risk

From many sources⁴⁵

Whole-grain foods
Dietary fiber, found in whole grains, many fruits and vegetables, and legumes such as black beans, chickpeas or lentils^a
Dairy foods, such as milk and plain yogurt
Foods rich in marine omega-3 fatty acids, such as fish and fish oils^b
Foods high in calcium, such as dairy foods and dark green leafy vegetables

From many sources⁴⁶

Processed meat (preserved by curing, salting, smoking, drying or canning)
Red meat
Alcohol

Some evidence shows that fiber’s benefit may involve the gut microbiome.⁴⁷
Some evidence of reduced risk in men but not women⁴⁸

A large study concluded that a moderate reduction in fat consumption did not reduce the risk of invasive colorectal cancer in postmenopausal women during more than eight years of follow-up.⁴⁹

Studies and expert assessments have further concluded that these foods and dietary choices may also lower risk of developing colorectal cancer or recurrence of adenomas:⁵⁰

Foods containing vitamin C, found in peppers, parsley, kale, kiwis, broccoli, Brussels sprouts, lemons, strawberries, oranges and other foods
Fish
Non-starchy vegetables such as dark green and leafy vegetables
Fruit
Foods rich in folate (Healthline), such as legumes (lentils, peas and dried beans), asparagus, eggs, leafy greens and other foods
Poultry, fish or legumes (dried beans, lentils and peas) instead of red meat
Food with anti-inflammatory components (see the list above), including flavonols (such as quercetin) and vitamin D

Although early investigations suggested a protective effect of high intake of raw and/or cooked garlic against colorectal cancer,⁵¹ more recent analyses show no protective effect.⁵²

Researchers evaluating the evidence across 80 meta-analyses of interventional and observational studies of colorectal cancer prevention found no evidence of a protective effect for tea, coffee, fish and soy products.⁵³

Evidence shows that these foods may increase risk of colorectal cancer:

Foods containing heme iron (red meat, chicken and fish) might increase the risk of colorectal cancer.⁵⁴
Foods with a high dietary inflammatory index:⁵⁵
- Red and processed meats
- Refined carbohydrates
- Fried foods
- Sugar-sweetened beverages
- Margarine, shortening and lard

Antioxidants

Prospective randomized trials have not shown that antioxidant supplements prevent colorectal adenoma or carcinomas.⁵⁶

B Vitamins

Higher dietary intakes of folate and riboflavin (vitamin B₂) are associated with decreased risk.⁵⁷ Eating foods higher in vitamin B₁₂ was also associated with lower risk.⁵⁸ and with an overall low-risk diet and lifestyle in a population at high risk for colorectal cancer.⁵⁹ Good sources of these nutrients:⁶⁰

Folate	Riboflavin	Vitamin B₁₂
Broccoli Brussels sprouts Leafy green vegetables (cabbage, kale, spring greens and spinach) Peas Legumes such as chickpeas and kidney beans	Eggs^a Fortified breakfast cereals Milk Mushrooms Plain yogurt	Fish Milk Cheese Eggs Fortified breakfast cereals

a. See recommendations about eggs in the Commentary section below.

Unlike the B vitamins listed above, dietary intake of vitamin B₆ shows mixed results:

Reducing risk of colorectal cancer in some studies⁶¹
Higher serum levels of vitamin B₆ was associated with reduced risk in 50- to 69-year-old men.⁶²
A large meta-analysis found a slight decrease in colorectal cancer risk associated with the higher level of vitamin B₆ intake. This decrease was not statistically significant, and dietary intake was not separated from supplement use.⁶³
Dietary B₆ intake greatly increased risk of rectal cancer in women in one study.⁶⁴
A large study of US women aged 45 years or more found that dietary intakes of folate and vitamin B₆ were associated with lower colorectal cancer risk only among women who were not taking supplements containing folate and vitamin B₆.⁶⁵

The takeaway with vitamin B₆is that its impact on colorectal cancer risk is uncertain. Benefits may apply only to specific groups or specific cancer types. To date, no compelling evidence suggests that the presence of vitamin B₆ should be a priority in your dietary choices.

Calcium and Magnesium

Higher intake of calcium in drinking water reduces risk of incidence and death from colon cancer.⁶⁶
Higher intake of dietary magnesium reduces risk of colorectal cancer, especially colon cancer.⁶⁷
With higher intake of magnesium or higher calcium-to-magnesium ratios, risk is also reduced for colorectal adenoma, but only in people with specific genes (genotypes).⁶⁸

Fiber

Fiber feeds the friendly bacteria in your gut, and so is considered a prebiotic. Fiber is fermented by intestinal microorganisms into short-chain fatty acids, the most abundant of which is butyrate. Butyrate is necessary for normal metabolism but is not derived directly from food—it has to be created by bacteria fermenting fiber. Patients with colorectal cancer tend to have lower levels of butyrate-producing bacteria than other people.

Butyrate may be a reason that fiber is connected to colorectal cancer prevention. Butyrate is selectively transported into the lining of the colon, where it is used by normal colon cells for much of their energy needs. However, in cancer cells it accumulates in parts of the cell where its action is to suppress cell growth, induce cell death (apoptosis) and promote differentiation. In cell studies, butyrate inhibits colorectal cancer cell growth.⁶⁹

Optimizing Your Terrain

Beneficial Foods

Butyrate (from fiber, see above) is a potent anti-inflammatory. It lessens inflammation related to colitis in both rodents and humans.⁷⁰
Green tea consumption decreased fasting glucose and glycated hemoglobin (HbA1c) concentrations.⁷¹
Cocoa is antioxidative and anti-inflammatory⁷²

Foods to Avoid

Diets high in cholesterol (WebMD) are linked to increased inflammation.⁷³

See Eating Well.

Moving More

Treating the Cancer

Participating in regular physical activity reduces mortality:

Managing Side Effects and Promoting Wellness

Physical activity benefits some side effects and overall quality of life:

Reducing Risk

The Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons recommends regular exercise after curative treatment of colon and rectal cancer.⁸⁹

See Moving More.

Managing Stress

Reducing Risk

Higher perceived stress is associated with increased risk of rectal cancer, but not colon cancer.⁹³

See Managing Stress.

Sleeping Well

Treating the Cancer

Sleep duration and timing may impact survival:

Managing Side Effects and Promoting Wellness

Reducing Risk

The Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons recommends regular sleep after curative treatment of colon and rectal cancer.¹⁰²

Improving Sleep

See Sleeping Well for more information.

Creating a Healing Environment

Reducing Risk

Several environmental exposures are associated with increased risk of colorectal cancer:¹⁰⁷

See Creating a Healing Environment.

Sharing Love and Support

Managing Side Effects and Promoting Wellness

In a systematic review, emotional support and reassurance when trying to deal with fear of cancer recurrence featured as the most prominent supportive care need of colorectal cancer patients, regardless of clinical stage or phase of treatment.¹⁰⁹

Reducing Risk

See Sharing Love and Support.

Exploring What Matters Now

Managing Side Effects and Promoting Wellness

See Exploring What Matters Now.

Beyond the 7 Healing Practices: Further Integrative Therapies

The Ultimate Guide to Cancer: DIY Research

This guide from Ralph Moss, PhD, BCCT advisor and leading chronicler of integrative cancer treatments, shows you how to use four of the main tools that doctors use to decide on the best cancer treatments. It will help you learn why some cancer treatments that look good in clinical trials may not work for “real world” patients. It will help you answer key questions that the doctor may be hesitant to answer in the detail you need to decide about treatment:

What are my chances of actually living longer if I take your treatment?
What are the likely side effects, and how long will they last?
What other treatment options are available?

Also see The Moss Reports for comprehensive guidance on treating colorectal cancer.

Conventional treatments are readily available. Complementary therapies can be useful to enhance conventional treatment effects, improve quality of life and possibly even extend life for those with colorectal cancer. Many complementary therapies―when chosen thoughtfully, reviewed with your oncology treatment team and used alongside conventional therapies—can become part of your integrative cancer care approach.

Therapies are grouped according to their effects:

Treating the cancer
Managing side effects and promoting wellness
Reducing risk
Optimizing Your Terrain

We present natural products in six groups:

Good clinical evidence of efficacy & safety, easy access
Good clinical evidence of efficacy & safety, limited access
Limited clinical evidence of efficacy but good safety, used in leading integrative programs
Limited clinical evidence of efficacy, or significant cautions, but potential significant benefit
Especially promising preclinical or emerging clinical evidence of efficacy and safety
Evidence of no efficacy or may be dangerous

Off-label, overlooked and novel cancer approaches (ONCAs) are grouped separately:

Group A: Good clinical evidence of efficacy
Group B: Limited clinical evidence of efficacy
Group C: Promising preclinical evidence only
Group D: Evidence of no efficacy or may be dangerous

Within each section, we list only groups containing applicable therapies.

Other integrative therapies and approaches are described but not categorized. See the full summaries as linked for more information on each of these therapies.

Treating the Cancer

Avoiding Drug Interactions during Treatment

Potentially life-threatening interactions between drugs are possible. For example, proton pump inhibitors (PPIs) can increase the risk for progression in colorectal cancer patients being treated with adjuvant CAPOX (capecitabine with oxaliplatin) or FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin). PPIs have a significant effect on both progression-free and overall survival.

Working against cancer growth or spread, improving survival, or working with other treatments or therapies to improve their anticancer action

Conventional Treatments

Conventional treatments for colorectal cancer include these:

Surgery (also see Surgery and Colorectal Cancer below)
Radiofrequency ablation
Cryosurgery
Chemotherapy
Radiation therapy
Targeted therapy
Immunotherapy

These treatments are explained on the National Cancer Institute website: Colorectal Cancer—Patient Version and Colorectal Cancer—Health Professional Version.

Newer conventional treatments and outcomes:

Pressurised intraperitoneal aerosol chemotherapy (PIPAC) is a relatively new treatment for patients with peritoneal metastases. A 2019 review found an objective clinical response of 71–86 percent for colorectal cancer (median survival of 16 months) with PIPAC. Repeated PIPAC did not have a negative effect on quality of life.¹¹⁸
Pulsed low-dose rate radiation therapy (PLDR-RT) delivers conventional radiation doses in pulses of small doses with intermittent pauses. A small study involved PLDR-RT for patients with rectal and other cancers of the pelvis. Patients had undergone radiation therapy to the pelvis previously. Twenty-three patients were treated with a curative intent and 15 were treated palliatively. At one year, 59 percent of patients treated for curative intent had a clinical, biochemical or radiographic response, and six of the 23 patients had no evidence of disease at their last follow-up. Among the patients treated palliatively, 61 percent had a clinical or radiographic response.¹¹⁹ This delivery also produces low rates of toxicity, along with reduced damage to noncancerous tissue and decreased repair of DNA damage in tumor cells.

Conventional treatments can be very expensive, and some treatments can cause long-lasting side effects.¹²⁰ We encourage you to explore the benefits, risks and costs of all options.

Delaying Treatment

Some providers offer a “watch-and-wait” approach for select rectal cancer patients who have had a clinical complete response after neoadjuvant therapy. While this approach has resulted in excellent rectal preservation and pelvic tumor control, a 2019 study found it has also resulted in worse survival and a higher incidence of distant progression in patients with local regrowth compared to those without local regrowth.¹²¹ A review and meta-analysis in late 2020 confirmed that delaying colorectal cancer treatment by a month or more increases the risk of dying.¹²²

Factors Influencing the Success of Treatment

Characteristics of both healthcare providers and the patient can impact the likelihood of success in treatment.

Natural Products

Antioxidants and Cancer Outcomes

Substances that act as antioxidants can have both antitumor and tumor-promoting effects, depending on several factors:¹²⁵

The specific antioxidant, plus the dose and format used
Characteristics of the patient: poor nutrition, smoking or high alcohol intakes may cause antioxidants to act as pro-oxidants and promote cancer growth
The tumor site and therapy: antioxidants can act as pro-oxidants in tissues with elevated partial pressures of oxygen.

Many substances can serve as antioxidants and are abundant in these food sources:

Allium sulphur compounds in leeks, onions and garlic
Anthocyanins in eggplant, grapes and berries
Beta-carotene in pumpkin, mangoes, apricots, carrots, spinach and parsley
Catechins in red wine, tea leaves (especially green tea), cocoa and berries
Copper in seafood, lean meat, milk and nuts
Coumaric acid in spices and berries
Cryptoxanthin in red bell peppers, pumpkin and mangoes
Flavonoids, particularly flavonols in tea leaves (especially green tea), citrus fruits, red wine, onions and apples
Indoles in broccoli, cabbage and cauliflower and other cruciferous vegetables
Isoflavonoids in soybeans, tofu, lentils, peas and milk
Lignans in sesame seeds, bran, whole grains and vegetables
Lutein in corn and green, leafy vegetables such as spinach
Lycopene in tomatoes, pink grapefruit and watermelon
Manganese in seafood, lean meat, milk and nuts
Polyphenols in thyme and oregano
Quercetin in apples, red wine and onions
Resveratrol in red and white wine, grapes, peanuts and berries
Selenium in Brazil nuts, seafood, animal organs, lean meat and whole grains
Vitamin A in liver, sweet potatoes, carrots, milk and egg yolks
Vitamin C in oranges, black currants, kiwifruit, mangoes, broccoli, spinach, bell peppers and strawberries
Vitamin E in vegetable oils such as wheat germ oil, avocados, nuts, seeds and whole grains
Zinc in seafood, lean meat, milk and nuts
Zoochemicals in red meat, organ meats and fish

Many of these individual antioxidants are also available as dietary supplements.

Antioxidants have mixed effects on chemotherapy toxicity, but no trials have assessed long-term effects of antioxidant supplementation during chemotherapy on recurrence or survival.

Mixed effects of antioxidants have been seen in reducing toxicity of radiotherapy, although not involving colorectal cancer patients. Observational studies in colorectal cancer patients have found that those taking self-prescribed multivitamins showed neither benefit nor harm regarding toxicity or survival.¹²⁶

Antioxidants may reduce chemotherapy and radiotherapy toxicity, but they also can make these treatments less effective. The anticancer effects of radiotherapy and certain chemotherapy drugs, including alkylating agents, anthracyclines, podophyllin derivatives, platinum complexes and camptothecins, may come from producing reactive oxygen species and increasing cell death. A 2014 review concluded that accumulating evidence “does not support the widespread use of antioxidants in patients with cancer.”¹²⁷

Antioxidants have shown little to no effect on reducing risk of colorectal cancer.¹²⁸ Some evidence shows benefit in reducing recurrence: patients receiving an antioxidant compound of selenium, zinc, vitamin A, vitamin C and vitamin E were significantly less likely to have an adenoma recurrence.¹²⁹

Use of tobacco and alcohol is an important consideration when considering antioxidant supplements. One analysis found that supplementation with antioxidants decreased the recurrence of colon adenomas among people who neither smoke nor drink alcohol, but use doubled the risk among participants who smoked and also drank more than one alcoholic drink per day.¹³⁰

Evidence and cautions regarding eating foods rich in antioxidants are described in Eating Well above, while those related to supplements are listed in the Natural Products sections.

Group 1: Good clinical evidence of efficacy & safety, easy access

These therapies may be widely used in integrative cancer protocols and traditional medical systems.

Therapy	Notes
Medicinal mushrooms	Turkey tail mushrooms or extracts: PSK (an extract of turkey tail mushrooms) improved both survival and disease-free survival of patients with advanced stomach and colorectal cancer or with curatively resected colorectal cancer.¹³¹ Improved survival in colorectal cancer.¹³² Improved 5-year disease-free survival and reduced lung metastases when used with oral Tegafur/Uracil¹³³ Improved recurrence-free survival, cancer death survival, and overall survival rates when added to chemotherapy treatment, but only among patients with diffuse nuclear accumulation-type beta-catenin activation¹³⁴ Improved 10-year survival when added to oral treatment with fluoropyrimidines¹³⁵ Among the botanicals most commonly used by oncology naturopaths for colorectal cancer¹³⁶ Shiitake mushroom extracts Improved survival in patients with gastric or colorectal cancer¹³⁷ Other medicinal mushrooms with preclinical evidence only:¹³⁸ Chaga mushroom (Inonotus obliquus) Pearl oyster mushroom (Pleurotus ostreatus) Indian or lung oyster mushroom (Pleurotus pulmonarius) Used in these programs and protocols: Alschuler & Gazella complementary approaches¹³⁹ McKinney protocols¹⁴⁰
Vitamin D	Reduced mortality with higher serum levels¹⁴¹ Increased five-year relapse-free survival in patients with digestive tract cancers who had baseline serum 25(OH)D levels between 20 and 40 ng/mL, but no improvement in five-year overall survival from vitamin D₃ supplementation after surgery¹⁴² Improved survival and progression-free survival in patients with advanced or metastatic colorectal cancer with high-dose vitamin D₃ supplementation compared to standard-dose vitamin D₃¹⁴³

Therapy

Notes

Medicinal mushrooms

Turkey tail mushrooms or extracts:

PSK (an extract of turkey tail mushrooms) improved both survival and disease-free survival of patients with advanced stomach and colorectal cancer or with curatively resected colorectal cancer.¹³¹
Improved survival in colorectal cancer.¹³²
Improved 5-year disease-free survival and reduced lung metastases when used with oral Tegafur/Uracil¹³³
Improved recurrence-free survival, cancer death survival, and overall survival rates when added to chemotherapy treatment, but only among patients with diffuse nuclear accumulation-type beta-catenin activation¹³⁴
Improved 10-year survival when added to oral treatment with fluoropyrimidines¹³⁵
Among the botanicals most commonly used by oncology naturopaths for colorectal cancer¹³⁶

Shiitake mushroom extracts

Improved survival in patients with gastric or colorectal cancer¹³⁷

Other medicinal mushrooms with preclinical evidence only:¹³⁸

Chaga mushroom (Inonotus obliquus)
Pearl oyster mushroom (Pleurotus ostreatus)
Indian or lung oyster mushroom (Pleurotus pulmonarius)

Used in these programs and protocols:

Alschuler & Gazella complementary approaches¹³⁹
McKinney protocols¹⁴⁰

Vitamin D

Reduced mortality with higher serum levels¹⁴¹
Increased five-year relapse-free survival in patients with digestive tract cancers who had baseline serum 25(OH)D levels between 20 and 40 ng/mL, but no improvement in five-year overall survival from vitamin D₃ supplementation after surgery¹⁴²
Improved survival and progression-free survival in patients with advanced or metastatic colorectal cancer with high-dose vitamin D₃ supplementation compared to standard-dose vitamin D₃¹⁴³

Group 3: Limited clinical evidence of efficacy but good safety, used in leading integrative programs

Therapy	Notes
Astragalus	Limited evidence of increased tumor response rate and survival when used with chemotherapy to treat colorectal cancer¹⁴⁴ Noteworthy preclinical evidence:¹⁴⁵ Works against proliferation (antiproliferative) Works against invasion (anti-invasive) Promotes cell death (proapoptotic) Induces cell cycle arrest Prevents the development of new blood vessels (anti-angiogenic) Formononetin, an astragalus extract, reduced metastasis and tumor growth in animals and reduced cell invasion and blood vessel development (angiogenesis) with tolerable toxicity Used in the Block program¹⁴⁶ in combination with several other natural products in conjunction with conventional treatment
Curcumin	Decreased serum TNF-α level (a marker of inflammation), increased cell death (apoptosis), and enhanced expression of p53 (a tumor suppressor gene) in tumor tissue in patients with colorectal cancer after diagnosis and before surgery¹⁴⁷ Significant tumor marker response and some clinical benefit, although no antitumor activity in a small trial of liposomal curcumin in metastatic advanced cancer¹⁴⁸ Reduced a marker of inflammation in a meta-analysis (not specific to people with cancer)¹⁴⁹ Well tolerated and effective with FOLFOX (5-fluorouracil, oxaliplatin, and gemcitabine)¹⁵⁰ with some evidence of improved survival¹⁵¹ Notable preclinical evidence of effects: Induced cell death (apoptosis) in colorectal cancer cells¹⁵² and several other modes of anticancer action¹⁵³ Enhanced effects of the chemotherapy drug irinotecan on colorectal cancer cells¹⁵⁴ Enhanced anticancer activity of the chemotherapeutic drug 5-fluorouracil¹⁵⁵ Inhibited and reversed EMT (epithelial-to-mesenchymal transition), a process involved in tumor progression, invasion, migration and metastasis, plus reduced resistance to chemotherapy¹⁵⁶ Used in these programs and protocols: Alschuler & Gazella complementary approaches¹⁵⁷ Bastyr University Integrative Oncology Research Center Lemole, Mehta & McKee protocols¹⁵⁸ McKinney protocols¹⁵⁹ Among the botanicals most commonly used by oncology naturopaths for colorectal cancer¹⁶⁰
Fermented wheat germ extract	Improved response to chemotherapy and radiotherapy, extending both progression-free survival and overall survival, including in advanced stages¹⁶¹ Notable preclinical effects: Interacted with 5-fluorouracil (5-FU) or dacarbazine (DTIC) in mouse models, reducing tumor size and metastasis¹⁶² Promoted cell death (apoptosis) in cancer cells,¹⁶³ including colon cancer cell lines¹⁶⁴ Reduced proliferation of cancer cells,¹⁶⁵ including colon cancer cell lines¹⁶⁶ Used in these protocols and programs: Block program¹⁶⁷ Parmar & Kazcor treatment plans¹⁶⁸
Green tea extracts/EGCG The effects of drinking tea are discussed above in Eating Well.	Inhibited tumor stem cell proliferation, prevented tumor production, and reduced risk of recurrence after surgery¹⁶⁹ Prevented the development and progression of precancerous lesions, such as colorectal adenomas,¹⁷⁰ and reduced incidence of metachronous (not concurrent) adenomas after colorectal adenomas were removed¹⁷¹ Notable preclinical evidence: Protected animals from colon cancer induced by azoxymethane (a substance used in cancer research to cause colon tumors in laboratory animals)¹⁷² Inhibited polyp formation in animals and suppressed small intestinal tumor formation in mice¹⁷³ Inhibited tumor incidence, with near-normal survival rate and restoration of normal colon architecture in rodents¹⁷⁴ Inhibited precancerous polyps and development of colon cancer in mice fed a high-fat diet¹⁷⁵ Inhibited development of intestinal, colon and stomach cancer¹⁷⁶ Used in these Programs and Protocols: Alschuler & Gazella complementary approaches¹⁷⁷ Block program¹⁷⁸ Lemole, Mehta & McKee protocols¹⁷⁹
Melatonin	Increased one-year survival rate and objective tumor regression rate in patients treated with melatonin and chemotherapy compared to those receiving chemotherapy alone (with several cancers including gastrointestinal tract neoplasms)¹⁸⁰ Increased one-year survival rate compared to supportive care alone or when combining subcutaneous low-dose interleukin-2 (a type of cytokine or immune protein that boosts the activity of certain immune cells) with melatonin¹⁸¹ Increased disease control in patients with metastatic colorectal cancer when added to treatment with irinotecan¹⁸² Used in these programs and protocols: Alschuler & Gazella complementary approaches¹⁸³ Block program¹⁸⁴ Lemole, Mehta & McKee protocols¹⁸⁵ McKinney protocols¹⁸⁶ Parmar & Kazcor treatment plans¹⁸⁷
Mistletoe (European)	Longer disease-free survival¹⁸⁸ Can be highly toxic if used inappropriately; see Cautions in the full review Used in the Parmar & Kazcor treatment plans¹⁸⁹
Omega-3 fatty acid supplements The effects of omega-3s in your diet are discussed above in Eating Well.	Lower risk of colorectal cancer-specific mortality with higher intake (from both diet and supplements) after diagnosis¹⁹⁰ Reduced length of hospital stay, but no reduction in noninfectious complications or mortality when taken before surgery in a nutritional supplement also including arginine and nucleotides¹⁹¹ No decrease in tumor size or improvement in patient survival times in a 2015 review¹⁹² Increased cell death (apoptosis) in the normal sigmoid colon with a dietary decrease in omega-6s and increase in omega-3s for two years¹⁹³ Eicosapentaenoic acid (EPA) effects: Improved overall survival in patients undergoing liver resection surgery for colorectal cancer liver metastases¹⁹⁴ Reduced extent of blood vessel networks consistent with reduced creation of new blood vessels to supply tumors (angiogenesis) with EPA use¹⁹⁵ Reduced crypt cell proliferation and increased cell death (apoptosis) in people with colorectal adenomas with three months of supplementation¹⁹⁶ Used in these programs and protocols: Alschuler & Gazella complementary approaches¹⁹⁷ Block program¹⁹⁸ Lemole, Mehta & McKee protocols¹⁹⁹ McKinney protocols²⁰⁰ Parmar & Kazcor treatment plans²⁰¹
Resveratrol	Increased markers of cell death (apoptosis) in cancerous liver tissue in patients with colorectal cancer and liver metastases²⁰² Reduced tumor cell proliferation by 5 percent in a small study²⁰³ Notable preclinical effects: Prevented formation of colon tumors and reduced their numbers and reduced the formation of small intestinal tumors by 70 percent in mice²⁰⁴ Sensitized colon cancer cells to 5-fluorouracil²⁰⁵ Used in these programs and protocols: Block program²⁰⁶ Lemole, Mehta & McKee protocols²⁰⁷ McKinney protocols²⁰⁸

Group 4: Potential significant benefit, but either limited clinical evidence of efficacy or significant cautions

May be used in leading integrative oncology programs. Therapies in this group may need more medical oversight and surveillance.

Therapy	Notes
Aged garlic extract (CAM Cancer) The effects of garlic in your diet are discussed above in Eating Well.	Reduced size and number of colon adenomas in colorectal cancer patients²⁰⁹ Caution regarding increased risk of colorectal cancer with use
Combinations of therapies	Hedyotis, astragalus and scutellaria Increased tumor response rates when used with oxaliplatin-based regimens in the palliative treatment of colorectal cancer²¹⁰ Kangai injection (KAI, ginseng, Astragali radix and kushen) Increased clinical effectiveness and survival time with in advanced colorectal cancer patients receiving chemotherapy²¹¹ LC09 (Astragalus membranaceus, flowers carthami, lithospermum, Geranium wilfordii, and Radix angelicae) Increased chemotherapy completion rate in colorectal cancer patients with chemotherapy-associated hand-foot syndrome²¹² MB-6, a combination of fermented soybean extract, green tea extract, Antrodia camphorata mycelia, spirulina, grape seed extract, and curcumin extract Enhanced chemotherapy effects and outcomes:²¹³ Reduced disease progression rate, incidence of adverse events (at least grade 4) and occurrence of increased serum creatinine (an indicator of kidney toxicity) in a small clinical study of patients with metastatic colorectal cancer when combined with leucovorin, 5-fluorouracil, and oxaliplatin compared to chemotherapy alone Increased the survival rate and life span of mice bearing colon cancer tumors when combined with chemotherapy as compared with chemotherapy alone Paeonia, curcuma, and sophora Increased tumor response rates when used with oxaliplatin-based regimens in the palliative treatment of colorectal cancer²¹⁴ Quxie Capsule, a combination of traditional Chinese medicine therapies Increased median overall survival, but not progression-free survival, in some small studies²¹⁵ but not all²¹⁶ Noteworthy preclinical evidence: Lower mean tumor weight in mice and increased cell death (apoptosis)²¹⁷
L-carnosine (WebMD)	Promoted cell death (apoptosis) when used with FOLFOX-6 regimen²¹⁸
Vitamin B₃ supplements	Increased 5-FU delivery to colorectal cancer liver metastases, but did not increase 5-FU retention or tissue exposure²¹⁹
Vitamin C supplementation or intravenous use	Associated with tumour regression in advanced colon cancer and improved toleration of standard therapy²²⁰ Improved survival in patients with many cancer types²²¹ Notable preclinical evidence:²²² High levels (with intravenous use) selectively kill colorectal cancer cells and impair their growth in mice Overcame chemoresistance to cetuximab in mutated colorectal cancer cells

Other therapies with preclinical evidence only for treating the cancer

Cocoa
Ginger
L-carnitine
Quercetin
Vitamin K₂

Group 5: Especially promising preclinical or emerging clinical evidence of efficacy and safety

Therapy	Notes
Arabinogalactan (WebMD)	Decreased tumor size and weight in mice, plus other anticancer activity²²³ Reduced liver metastases and prolonged survival of animals when administered with D-galactose²²⁴
Grape seed extract	Inhibited lung metastasis in mice²²⁵ Inhibited cell proliferation and increased cell death (apoptosis) in tumors in mice²²⁶ Enhanced inhibition of cancer cell growth from treatment with 5-FU in rats²²⁷
Indole-3-carbinol supplements (About Herbs)	Reduced incidence and multiple occurrences per animal of colonic adenomatous polyps in mice²²⁸
L-glycine (Healthline)	Decreased liver metastases tumor volume and microvascular density when combined with FOLFOX in animals²²⁹
Probiotics	Suppressed colon tumor incidence/number and size and increased cell death (apoptosis) in animals²³⁰

Off-label, Overlooked or Novel Cancer Approaches (ONCAs)

These therapies have exciting potential and/or proven benefits. However, some carry higher risks of side effects, interactions with other treatments and other adverse medical events than other therapies we review. Cautions are noted with each therapy, and we strongly urge you to consult your doctor before using these therapies—even over-the-counter drugs—for cancer treatment. We also note whether a prescription is needed or if a therapy is not widely available.

Group A: Good clinical evidence of efficacy

May be used in integrative protocols and programs

Therapy	Notes
Aspirin	Improved survival in general,²³¹ but considerable variation in individual study findings depending on study specifics: Improved overall survival when used after diagnosis but not before diagnosis, and only in patients positive for COX-2 expression (which influences tumor invasiveness and inflammatory responses) and mutated PIK3CA tumors²³² Improved colorectal cancer-specific survival and lower odds of diagnosis with distant metastases with long-term regular use of aspirin (more than 15 times per month) before diagnosis; beginning regular aspirin use only after diagnosis improved survival compared with no aspirin use²³³ Improved survival in those with wild-type BRAF tumors but not mutated BRAF tumors²³⁴ or with PI3K mutation²³⁵ Improved all-cause and cancer-related survival at varying doses, regardless of body mass index²³⁶ Improved survival for type II diabetes patients with stage 2 and 3 colorectal cancer treated with both aspirin and metformin²³⁷ Improved survival in tumors with low PD-LI expression (which inhibits immune action against tumors) wth aspirin use with immunotherapy²³⁸ Improved five-year progression-free survival and a lower risk of developing metastasis²³⁹ Inhibited gene mutations which can contribute to uncontrolled proliferation of cells and also induced cell death (apoptosis), improving survival and reducing recurrence²⁴⁰ Induced cell death (apoptosis), improving survival and reducing recurrence in metastatic colorectal cancer²⁴¹ Slightly higher mortality among elderly colorectal cancer patients taking daily low-dose aspirin²⁴² Slowed polyp progression in patients with hereditary nonpolyposis colorectal cancer²⁴³ Increased rate of tumor downstaging with use during neo-adjuvant therapy (therapy prior to the main therapy)²⁴⁴ and during preoperative chemoradiation for rectal cancer²⁴⁵ No improvements in toxicity or response rate (pathological complete response rate) in rectal cancer patients undergoing neo-adjuvant long-course radiation therapy²⁴⁶ Significan cautions regarding gastrointestinal bleeding and other risks with use; see Cautions on our Aspirin and Non-steroidal Anti-inflammatory Drugs page Used in these programs and protocols: Block program²⁴⁷ Chang strategies²⁴⁸
Chronomodulated therapies	Higher rates of complete and partial remissions compared to those getting continuous infusion chemotherapy.²⁴⁹ Prolonged median overall survival in men, but not always in women²⁵⁰ Improved tumor response²⁵¹ including longer median time to treatment failure compared to constant-rate infusion²⁵² Use of higher doses of 5-FU with greater objective response, progression-free survival and median survival in patients with previously untreated metastatic colorectal cancer²⁵³ No difference in survival in four-day chronomodulated combination of 5-fluorouracil and oxaliplatin versus two-day FOLFOX2 (chemotherapy regimen containing folinic acid (leucovorin), fluorouracil, and oxaliplatin)²⁵⁴ Improved tolerability of chemotherapy and near doubling of anticancer activity with oxaliplatin and 5-FU-leucovorin given through chronomodulated vs. constant-rate administration²⁵⁵ Improved outcomes and survival with metastasis²⁵⁶ Improved survival (compared to other studies) with chronotherapy compared to continuous infusion in a small study of people with stage 3-4 colon cancer, although the numbers were too small to draw conclusions²⁵⁷ Optimal chronomodulated schedules corresponded to peak delivery rates at 1am or 4am for 5-fluorouracil-leucovorin, at 1pm or 4pm for oxaliplatin, and at 4pm for carboplatin.²⁵⁸ Influenced all markers of enzyme activity (phenotype markers) important for tolerability and efficacy of fluoropyrimidine drugs²⁵⁹ Notable preclinical evidence: Findings of best times to administer specific chemotherapy drugs: oxaliplatin 1-4pm, 5-FU early morning before 6am, Irinotecan morning 6-9am²⁶⁰
Metformin	Lower overall mortality and colorectal cancer-specific mortality.²⁶¹ May improve overall survival in colorectal cancer patients with metabolic syndrome²⁶² or diabetes²⁶³ Increased disease control rate at week 12 when combined with irinotecan²⁶⁴ or at week 8 with 5-fluorouracil²⁶⁵ in patients with measurable metastatic colorectal cancer Reversed the proliferation of colorectal cancer cells enhanced by d-(+)-glucose administration and considerably increased sensitivity to oxaliplatin chemotherapy²⁶⁶ May be a useful adjuvant therapy, especially in colorectal cancer patients receiving radical radiotherapy.²⁶⁷ Notable preclinical evidence: Enabled normal SCID (severe combined immunodeficiency) mice not deficient in T cells to reject solid tumors and increased the number of tumor-infiltrating lymphocytes and protected them from cell death (apoptosis) and exhaustion²⁶⁸ May increase the efficacy of immunotherapy²⁶⁹ Requires a prescription from a licensed physician Used in the Block program²⁷⁰
Statins	Overall, most studies show improved survival (overall, progression-free, recurrence-free, disease-free survival) and prognosis, although differences are seen depending on the cancer treatment used and patient characteristics. Evidence of positive treatment effects: Decreased risk of all-cause mortality, and for all types of cancer combined, reductions in cancer-specific mortality and improvements in progression-free survival, recurrence-free survival and disease-free survival; improvements in recurrence-free survival were significantly greater with use after diagnosis than before diagnosis²⁷¹ Similar survival outcomes to patients mean BMI 24-25 treated with lifestyle modifications²⁷² (Note: lifestyle modifications, such as the 7 Healing Practices, involve far fewer side effects and risks compared to statins.) Reduced all-cause and cancer-specific mortality with statin uses both before and after diagnosis in some reviews and meta-analyses²⁷³ and improved overall survival in a separate retrospective cohort review²⁷⁴ Improved prognosis in large-scale cohort studies²⁷⁵ Better prognosis of surgically resected colorectal cancer in one review,²⁷⁶ although another study found no differences in disease-free survival, recurrence-free survival or all-cause mortality in patients undergoing neoadjuvant chemoradiotherapy and resection for rectal cancer²⁷⁷ Reduced proportion of late-stage (at diagnosis) colorectal cancer cases among users of lipophilic statins in a large retrospective study of women²⁷⁸ and a population-based case-control study²⁷⁹ Higher rate of tumor downstaging (reduction in the cancer stage) with use during neoadjuvant therapy²⁸⁰ A combination regimen of simvastatin, cetuximab and irinotecan showed promising safety and efficacy in KRAS-mutated colorectal cancer patients for whom irinotecan and oxaliplatin had failed.²⁸¹ Evidence of no improvement: No improved progression-free survival and overall survival in some analyses,²⁸² perhaps due to poor trial design²⁸³ Noteworthy preclinical evidence: Anticancer proliferation effects in resistant colorectal cancer cells when used with chemotherapy drugs; interfered with insulin-like growth factor 1 receptor (IGF-1R) signaling, which is known to promote cancer cell survival and proliferation; and other anticancer effects²⁸⁴ Only natural statins (simvastatin, mevastatin and lovastatin) suppressed NF-kB activation. NF-kB, a group of proteins that help control cell growth and survival, may be excessive or overactive in some types of cancer cells, which may lead to cancer cell growth.²⁸⁵ Pretreatment with lovastatin significantly increased cell death (apoptosis) induced by 5-fluorouracil (5-FU) or cisplatin in colon cancer cell lines.²⁸⁶ Requires a prescription from a licensed physician Note significant cautions in our Statins page. Used in the Block program²⁸⁷

Group B: Limited clinical evidence of efficacy

May be used in integrative protocols and programs

Therapy	Notes
Artemisinin derivatives and artesunate	Worked against tumor proliferation (antiproliferative) in a small trial²⁸⁸ A 2018 review of clinical artesunate and artemisinin derivatives did not find efficacy in the treatment of colorectal cancer.²⁸⁹ Notable preclinical evidence: Tumor growth delay and tumor shrinkage in mice grafted with human colorectal cancer cells²⁹⁰ Dihydroartemisinin (DHA) sensitized resistant cells to 5-FU.²⁹¹ DHA increased the rate at which doxorubicin inhibits tumors, with a further increase if DHA and doxorubicin were co-encapsulated into mannosylated liposomes.²⁹² 10-(4-phenyl-1H-1,2,3- triazol)-artemisinin (5a) controlled acquired drug resistance and recovered the anticancer effect of paclitaxel on cancer cells.²⁹³ Note cautions in our Artemisinin and Artesunate page. Used in the Parmar & Kazcor treatment plans²⁹⁴
Cimetidine (Tagamet)	May improve survival in patients with colorectal cancer,²⁹⁵ such as when used as adjuncts (supplementary therapy) to surgery intended as a cure,²⁹⁶ although not all studies found benefit²⁹⁷ May be more effective in those with less tumor burden and better immune function and in cancers that are more likely to trigger immune responses (have a higher antigenic potential)²⁹⁸ Increased response of tumor-infiltrating lymphocytes when used 10 days before and seven days after surgery²⁹⁹ May reduce the immunosuppressive effect of surgery in Dukes Stage A, B and C tumors Noteworthy preclinical evidence: Worked against proliferation and adhesion of cancer cells and increased production of antitumor cytokines³⁰⁰ Reduced formation of blood vessels to supply tumors (angiogenesis)³⁰¹ Used in these programs and protocols: Block program³⁰² Chang strategies³⁰³
Chloroquine (Medline Plus)	Limited evidence of chloroquine’s efficacy in overcoming resistance to chemotherapy in colorectal cancer patients³⁰⁴ Noteworthy preclinical evidence: Potentiated (enabled/enhanced) anticancer effect of 5-fluorouracil on colon cancer cells³⁰⁵ Inhibited autophagy (cell self-cleaning) and enhanced apoptosis (cell death) in colorectal cancer cells when added to 5-fluorouracil (5-FU) and oxaliplatin, when used with bortezomib, or in combination with 5-FU and radiation therapy³⁰⁶ Requires a prescription from a licensed physician
Copper chelation with tetrathiomolybdate (TM) and other substances	No notable improvements in time to progression, but also no increase in toxicity or interference with effects of irinotecan, 5-fluorouracil, and leucovorin in a small clinical trial of in patients with advanced metastatic colorectal cancer³⁰⁷ TM showed anti-angiogenic activity (prevents the formation of new blood vessels) while avoiding clinical copper deficiency.³⁰⁸ Noteworthy preclinical evidence: Antitumor activity in human colon cancer cells grafted onto mice³⁰⁹ Affected proliferation, survival and migration in colorectal cancer cells with BRAF mutation, a gene mutation which may increase the growth and spread of cancer cells. Copper chelation also decreased the cloning potential of BRAF cells otherwise resistant to drugs targeting the BRAF mutation³¹⁰ Melon extracts, especially melon peel aqueous extract, showed copper-chelating properties in lab studies.³¹¹ Copper chelators plus iron chelators combined with DHA and 5-FU in colorectal cancer cells overcame drug resistance through increased cell death (apoptosis).³¹² Used in these programs and protocols: Block program³¹³ Parmar & Kazcor treatment plans³¹⁴ BCCT is aware of several reputable integrative oncologists seeing positive responses to using copper chelation in patients with advanced solid tumors.
Nelfinavir (Virocept) (Medline Plus)	May improve tumor regression compared to radiotherapy alone³¹⁵ May reduce tumors when used with radiotherapy in combination with capecitabine³¹⁶ Noteworthy preclinical evidence: Inhibited tumor growth in mice³¹⁷ . and cell studies³¹⁸ Note significant cautions and interactions with other drugs: ask your doctor or pharmacist.
Nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin (MedicineNet)	No improvement in disease-free survival or overall survival among people with stage 3 colon cancer with three years of celecoxib (Celebrex) added to standard adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in a large randomized trial³¹⁹ Improved overall survival in KRAS wild-type mutations but not KRAS-mutated patients when combined with cetuximab targeted therapy³²⁰ Inconclusive clinical results of survival benefit overall, but improved survival with tumors with low expression of PD-LI (programmed cell-death ligand, a molecule on the surface of tumor cells that inhibits the antitumor function of T cells)³²¹ Noteworthy preclinical evidence: Reduced resistance to chemotherapy in colorectal cancer³²² . Improved antitumor immune response and tumor eradication when combined with anti-PD1 monoclonal antibody³²³ Antiproliferative effects (reduced tumor growth) from diclofenac in animal studies³²⁴ Significan cautions regarding gastrointestinal bleeding and other risks with use; see Cautions on our Aspirin and Non-steroidal Anti-inflammatory Drugs page
Rapamycin (sirolimus)	High response and cancer control rates when rapamycin and hydroxychloroquine were added to metronomic chemotherapy (also called low-dose chemotherapy) for refractory metastatic solid tumors in a small group of patients who didn't respond to first-line metronomic chemotherapy³²⁵ Tolerated by most patients when used with bevacizumab, at lower cost than other mTOR inhibitors, but without significant treatment effects in patients with pathologically confirmed advanced solid tumors for which standard curative or palliative measures either do not exist or were no longer effective³²⁶ Noteworthy preclinical evidence: Enhanced response to erlotinib, inhibiting cell growth pathways in cell and animal models³²⁷ Requires a prescription from a licensed physician Note cautions when using after surgery.

Group C: Promising preclinical evidence only

Therapy	Notes
Bisphosphonates (Cancer Research UK), including clodronate (Canada) and zoledronic acid (Reclast, Zometa),	Clodronate liposomes decreased tumor numbers in mice.³²⁸ Zoledronic acid reduced cell viability and growth.³²⁹ Zoledronic acid or a derivative (another drug made from zoledronic acid) regulated cell self-cleaning (autophagy) and induced cell death (apoptosis) in colorectal cancer cells³³⁰ Note several side effects.

Diets and Metabolic Therapies

Short-term fasting (noteworthy preclinical evidence)

As effective as chemotherapy in delaying the progression of a wide range of cancers in animals³³¹
Reduced tumor progression in mice with complete fasts of one to two days or alternating fasting and non-fasting days³³²
Synergistic effect with vitamin C in delaying tumor progression in mice with colorectal cancer with the KRAS gene mutation³³³
Enhanced the effect of virus-mediated cell killing in colorectal cancer cells while protecting normal colon cells³³⁴
Alternate-day fasting inhibited tumor growth in mice without causing weight loss.³³⁵
Note cautions on the Intermittent Fasting page.

Manipulative and Body-Based Methods

Acupuncture and Electroacupuncture

Reduced average tumor size and other indicators of cancer using nanoporous needles in animals (needles that have micro/nano-scale pores on their surface)³³⁶

Therapies Using Heat, Sound, Light or Cutting-edge Radiotherapy

Hyperthermia

Local or regional hyperthermia:
- Improved overall survival time of patients with liver metastases from colorectal cancer compared to chemotherapy alone³³⁷
- "Excellent survival outcomes in optimally selected patients" with colorectal cancer who have peritoneal metastases treated with systemic chemotherapy, then cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Both oxaliplatin and mitomycin C had comparable effectiveness when given in the intraperitoneal cavity. (Report on a presentation at the ESMO 22nd World Congress on Gastrointestinal Cancer)³³⁸
- Greater rates of complete response and regression of the primary tumor³³⁹
- No improved survival and an increased risk of adverse events in colorectal cancer patients when adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone³⁴⁰
Whole-body hyperthermia:
- Improved response to chemotherapy and potentially improved survival³⁴¹

Managing Side Effects and Promoting Wellness

Inflammation and Side Effects

As integrative oncologist and BCCT advisor Keith Block, MD, explains: Inflammation can bring on cachexia—the severe wasting syndrome common among patients with solid tumors—and, especially, metastases. Cachexia, which is particularly common in cancers of the pancreas, colon and lung, can lead to the rapid breakdown of muscle, including the heart muscle.³⁴²

Inflammation is associated with cachexia,³⁴³ as inflammatory cytokines cause reduced appetite and abnormal metabolism of proteins, fats and carbohydrates. All this leads to loss of muscle and weight.³⁴⁴

Side effects of the cancer and of treatments can dramatically impact your quality of life. A 2009 review summarizes: “Although issues and symptoms were most prominent during the first three years, long-term effects of treatment can persist and include fatigue, sleep difficulty, fear of recurrence, anxiety, depression, negative body image, sensory neuropathy, gastrointestinal problems, urinary incontinence, and sexual dysfunction.”³⁴⁵ Therapies that address side effects can greatly improve your well-being and improve life for you and your caregivers.

Conventional Treatments

Pulsed low-dose rate radiation therapy (PLDR-RT) delivers conventional radiation doses in pulses of small doses with intermittent pauses. A small study involved PLDR-RT for rectal and other cancers of the pelvis. Of the 50 percent of patients who reported pain at the local site before treatment, 68 percent reported an improvement in pain after PLDT-RT.³⁴⁶

Natural Products

Group 1: Good clinical evidence of efficacy & safety, easy access

These therapies may be widely used in integrative cancer protocols and traditional medical systems.

Therapy	Notes
Astragalus	Improved quality of life and reduced adverse reactions—including nausea and vomiting, diarrhea, neurotoxicity, neutropenia (low count of white blood cells called neutrophils), anemia, thrombocytopenia (low count of platelets) and leukopenia (low count of white blood cells)―when used during chemotherapy in treating colorectal cancer³⁴⁷ Reduced incidence of chemotherapy-induced neutropenia (low count of white blood cells called neutrophils, leading to increased susceptibility to infection) when administered orally with oxaliplatin³⁴⁸ Improved appetite, sleep and quality of life, reduced fatigue, pain, inflammation, nausea and vomiting with advanced metastatic cancer using IV (intravenous) astragalus polysaccharides³⁴⁹ Reduced chemotherapy-induced nausea and vomiting with oxaliplatin; regulation of gastrointestinal motility and gastroprotective effects³⁵⁰ Reduced fatigue and immune suppression caused by chemotherapy³⁵¹ Reduced diarrhea related to chemotherapy for colorectal cancer³⁵² Protected nervous system tissue³⁵³ and relieved pain from nerve damage induced by oxaliplatin without affecting the anticancer effect of chemotherapy³⁵⁴ Reduced incidence and severity of chemotherapy-induced peripheral neuropathy and improved nerve function and functional performance in people with various types of cancer (mostly gastrointestinal/colorectal), in some studies improving the response when used with western analgesics³⁵⁵ Reduced neurotoxicity when used during chemotherapy for colorectal cancer³⁵⁶
Curcumin	Improved quality of life in patients with solid tumors receiving standard chemotherapy regimens and a bioavailability-enhanced curcumin preparation in small studies³⁵⁷ Increased body weight and prevented weakness and wasting (cachexia) in colorectal cancer patients after diagnosis and before surgery³⁵⁸ and in general.³⁵⁹ Reduced several side effects of chemo- and radiotherapy, including mucositis, mouth and throat ulcers, swallowing problems, nausea and vomiting), swelling (erythema), skin lesions and weakness, and was protective of the liver³⁶⁰ Reduced treatment symptoms such as nausea, constipation, diarrhea, soreness and ulceration with the Meriva® formulation³⁶¹ Reduced pain from chemo- and radiotherapy³⁶² Reduced incidence of adverse events (at least grade 4) and occurrence of increased serum creatinine (an indicator of kidney toxicity) in people with colorectal cancer³⁶³
Ginger The effects of ginger in your diet are discussed above in Eating Well.	Protected from and worked against toxicities from chemicals and radiation³⁶⁴ Reduced nausea and vomiting from chemotherapy and following surgery³⁶⁵
L-glutamine, also known as glutamine	During chemotherapy: Reduced incidence and severity of oxaliplatin-induced peripheral neuropathy with no significant impact on response to chemotherapy³⁶⁶ Reduced severity of peripheral neuropathy associated with paclitaxel treatment at high doses (10 g orally, three times a day for 4 days)³⁶⁷ but not low doses (500 mg three times a day)³⁶⁸ Reduced some side effects induced by chemotherapy such as gut mucositis (inflammation in the lining of the digestive tract) and diarrhea, and improved wound healing after surgery³⁶⁹ Reduced duration of diarrhea but no improvement in severity of diarrhea during chemotherapy in a 2012 meta-analysis³⁷⁰ Decreased nausea/vomiting and diarrhea during chemotherapy with intravenous alanyl-glutamine dipeptide use³⁷¹ Reduced oral mucositis,³⁷² diarrhea and average number of loperamide tablets taken during treatment with 5-Fluorouracil (5-FU)³⁷³ No significant decrease in grade 3–4 non-hematological toxicities (toxicities other than a decrease in blood cell production) among patients undergoing chemotherapy³⁷⁴ During radiation or combination therapy: Reduced severity of radiation-induced diarrhea and reduced need for treatment breaks with 15 g of oral glutamine three times daily,³⁷⁵ but no improvement with 30 g per day in three doses during preoperative radiochemotherapy³⁷⁶ Failed to prevent the development of enteritis (inflammation of the small intestine) during radiotherapy³⁷⁷ BCCT advisor Keith Block, MD, provides guidance to discontinue after treatment ends.³⁷⁸
Melatonin	Prevented or minimized the unfavorable effects of radiotherapy on reduced blood cell count in rectal cancer patients³⁷⁹ Reduced frequency of chemotherapy-induced side effects:³⁸⁰ Weakness (asthenia) Low blood platelet count (thrombocytopenia) Inflammation of the mouth and lips (stomatitis) Damage to the heart (cardiotoxicity) Damage to nerves (neurotoxicity) Loss of strength and energy Reduced toxicity and the typical postsurgical reduction in lymphocytes when administered with low-dose interleukin-2 before surgery for gastrointestinal tract tumors³⁸¹
Omega-3 fatty acid supplements The effects of omega-3s in your diet are discussed above in Eating Well.	Reduced incidence of peripheral neuropathy and promoted weight maintenance or gain during cancer treatment, and improved scores of physical function and global health status³⁸² Promoted body weight maintenance during chemotherapy³⁸³ or weight gain³⁸⁴ and reduced muscle loss³⁸⁵ Improved quality of life and chemotherapy-related side effects including appetite loss, fatigue, pain, nausea and vomiting and diarrhea with a combination omega-3 fatty acid and strain-specific probiotic³⁸⁶ Reduced postoperative infectious complications and hospital stay after colorectal cancer surgery in one study³⁸⁷ but no improvement in infectious or non-infectious postoperative complications in another³⁸⁸ Eicosapentaenoic acid (EPA) alone Increased weight and improved scores of health-related quality of life, with a trend toward fewer interruptions of chemotherapy treatment³⁸⁹ Increased mean weight and energy levels in an uncontrolled trial of colorectal cancer patients undergoing chemotherapy with folinic acid, 5-fluorouracil, irinotecan (FOLFIRI)³⁹⁰ Reduced deterioration of nutritional status resulting from antineoplastic therapies (therapies to block the formation of neoplasms) by improving calorie and protein intake³⁹¹
Probiotics	Reduced incidence of diarrhea induced by chemoradiotherapy, especially grade 2 or higher³⁹² Reduced the portion of colorectal cancer patients experiencing irritable bowel symptoms or symptoms of depression, and improved function-related quality of life and cancer-related quality of life scores in a small trial³⁹³ Conflicting findings on whether the use of prebiotics, probiotics or synbiotics at the time of surgery in patients undergoing colorectal cancer surgery reduces the development of infectious complications³⁹⁴

Group 2: Good clinical evidence of efficacy & safety, limited access

Some may require a prescription, for example.

Therapy	Notes
Medical cannabis and cannabinoids	A 2018 review from the National Academy of Sciences, Engineering and Medicine drew these conclusions:³⁹⁵ Effective for treating pain in adults and chemotherapy-induced nausea and vomiting (Conclusive or substantial evidence) Improved secondary sleep disturbances (moderate evidence) Insufficient evidence of improved appetite or anxiety Improvements in several side effects, including these in a prospective study in Israel:³⁹⁶ Sleep problems Pain Weakness and fatigue Digestion problems Anxiety and depression Nausea and vomiting Lack of appetite No improvement in reducing pain, sleep problems or opioid use among cancer patients with moderate and severe pain despite opioid therapy in a separate 2019 review from Germany and Canada³⁹⁷ Access varies by country or US state, with moderately easy access in some areas and no or very limited legal access in others

Therapy

Notes

Medical cannabis and cannabinoids

A 2018 review from the National Academy of Sciences, Engineering and Medicine drew these conclusions:³⁹⁵
- Effective for treating pain in adults and chemotherapy-induced nausea and vomiting (Conclusive or substantial evidence)
- Improved secondary sleep disturbances (moderate evidence)
- Insufficient evidence of improved appetite or anxiety
Improvements in several side effects, including these in a prospective study in Israel:³⁹⁶
- Sleep problems
- Pain
- Weakness and fatigue
- Digestion problems
- Anxiety and depression
- Nausea and vomiting
- Lack of appetite
No improvement in reducing pain, sleep problems or opioid use among cancer patients with moderate and severe pain despite opioid therapy in a separate 2019 review from Germany and Canada³⁹⁷
Access varies by country or US state, with moderately easy access in some areas and no or very limited legal access in others

Group 3: Limited clinical evidence of efficacy but good safety, used in leading integrative programs

Therapy	Notes
Glutathione	Reduced neurotoxicity during oxaliplatin/5-fluorouracil/leucovorin (FOLFOX) regimen without impairing the activities of the the drugs in the body (pharmacokinetics) or the formation of platinum-DNA adducts (which stop cancer cells from dividing)³⁹⁸ Prevented severe chronic neurotoxicity induced by chemotherapy³⁹⁹ Used in the Block program⁴⁰⁰
Magnesium (About Herbs) Evidence regarding magnesium in your diet is listed above in Eating Well.	Deficiency is associated with personality changes including apathy, depression, agitation, confusion, anxiety, panic attack disorders, disrupted sleep patterns and delirium;⁴⁰¹ supplementation reduces anxiety in animals and people⁴⁰² Used in the Block program⁴⁰³
Mistletoe (European)	Lower cancer-related fatigue⁴⁰⁴ Fewer reactions related to adjuvant (supplemental) therapy and fewer persisting symptoms⁴⁰⁵ Fewer adverse events and lower rates of discontinuation of standard oncological treatment⁴⁰⁶ Can be highly toxic if used inappropriately; see Cautions in the full review Used in these programs and protocols: Alschuler & Gazella complementary approaches⁴⁰⁷ McKinney protocols⁴⁰⁸ Parmar & Kazcor treatment plans⁴⁰⁹
N-acetylcysteine (About Herbs)	Reduced the incidence of oxaliplatin‐induced neuropathy in colon cancer patients in two small trials,⁴¹⁰ but reviews find insufficient evidence to recommend it for treating or preventing chemotherapy-induced peripheral neuropathy (CIPN).⁴¹¹ Used in the Block program⁴¹² for reducing peripheral neuropathy

Group 4: Potential significant benefit, but either limited clinical evidence of efficacy or significant cautions

May be used in leading integrative oncology programs. Therapies in this group may need more medical oversight and surveillance.

Therapy	Notes
Combinations of therapies	Astragalus membranaceus and Jiaozhen Protected against intestinal barrier dysfunction in postoperative colorectal cancer patients⁴¹³ Calcium and magnesium (intravenous) Two studies found positive effects: Delayed time to onset of grade 2 sensory neurotoxicity and reduced chronic, cumulative sensory neurotoxicity and acute muscle spasms induced by oxaliplatin (FOLFOX) in adjuvant colon cancer⁴¹⁴ Outcomes with calcium and magnesium infusions among patients treated with oxaliplatin plus 5-fluorouracil and leucovorin for advanced colorectal cancer:⁴¹⁵ Reduced incidence and intensity of acute oxaliplatin-induced symptoms Possibly delayed cumulative neuropathy and more rapid recovery from neuropathy Lower rate of treatment termination for any type of toxicity Less severe and prolonged weakness or lack of energy (asthenia) Higher likelihood of maintaining body weight But a review of these studies concluded not enough evidence showed reduced oxaliplatin-induced neurotoxicity⁴¹⁶ Kangai injection (KAI, ginseng, Astragali radix and kushen) Reduced neurotoxicity when used during chemotherapy for colorectal cancer⁴¹⁷ LC09 (Astragalus membranaceus, flowers carthami, lithospermum, Geranium wilfordii, and Radix angelicae) Decreased pain in colorectal cancer patients with chemotherapy-associated hand-foot syndrome⁴¹⁸ Medroxyprogesterone or megestrol acetate, eicosapentaenoic acid, L-carnitine and thalidomide Increased lean-body mass, decreased resting energy expenditure, improved fatigue and appetite, improved performance status in patients with cachexia (weakness and wasting)⁴¹⁹ Quxie Capsule, a combination of traditional Chinese medicine therapies Improved symptoms and quality of life in a small study⁴²⁰
Curcumin	Reduced several side effects of chemo- and radiotherapy; protective of the liver⁴²¹ Improved health-related quality of life,⁴²² including in patients with solid tumors under standard chemotherapy regimens⁴²³ Prevented cachexia (weakness and wasting) and increased body weight in colorectal cancer patients after diagnosis and before surgery⁴²⁴ A topical turmeric-based cream reduced radiotherapy-induced dermatitis.⁴²⁵ Notable preclinical evidence: Protective or nerves,⁴²⁶ preventing the initiation and development of peripheral neurotoxicity and reducing oxaliplatin-induced neurotoxicity⁴²⁷
Fermented wheat germ extract	Improved quality of life⁴²⁸ and improved or reduced side effects of conventional treatment⁴²⁹ in limited clinical trials
L-carnosine (WebMD)	Reduced oxaliplatin-induced peripheral neuropathy in colorectal cancer patients⁴³⁰
Selenium supplements	Reduced blood cell toxicity but no effect on kidney or hearing toxicity during cisplatin use⁴³¹
Vitamin B supplements	Some evidence of reduced chemotherapy-induced peripheral neuropathy (CIPN), which may vary according to the specific B vitamin used⁴³² Reduced pain with methylcobalamin, a form of vitamin B₁₂⁴³³
Vitamin C (intravenous)	Improved global health/quality of life—including physical, role, emotional, and cognitive functions—and lower scores for fatigue, nausea and vomiting, pain and appetite loss among terminal cancer patients⁴³⁴ and newly diagnosed cancer patients⁴³⁵ Decreased pain following laparoscopic colectomy and a case report of reduced symptoms from standard therapy with intravenous ascorbic acid⁴³⁶
Vitamin E supplementation	Reduced cisplatin-induced neuropathy, but no benefits seen with taxane neuropathy, oxaliplatin-induced peripheral neuropathy, anthracycline cardiotoxicity, or general carboplatin toxicity⁴³⁷ Reduced radiotherapy toxicity⁴³⁸

Group 5 Especially promising preclinical or emerging clinical evidence of efficacy and safety

Therapy	Notes
Aged garlic extract (CAM Cancer) The effects of garlic in your diet are discussed above in Eating Well.	Reduced damage of the small intestine from methotrexate in rats⁴³⁹ Caution regarding increased risk of colorectal cancer with use Used in the Block program⁴⁴⁰ for radiation enteritis
Grape seed extract	Reduced damage to the lining of the colon (mucositis) in rats⁴⁴¹
L-glycine (Healthline)	Diminished liver and kidney injury caused by toxicants and drugs, including chemotherapy-induced liver injury, and protected stomach lining (gastric mucosa) against ulcers induced by chemicals or stress⁴⁴²

Therapy

Notes

Aged garlic extract (CAM Cancer)

The effects of garlic in your diet are discussed above in Eating Well.

Reduced damage of the small intestine from methotrexate in rats⁴³⁹
Caution regarding increased risk of colorectal cancer with use
Used in the Block program⁴⁴⁰ for radiation enteritis

Grape seed extract

Reduced damage to the lining of the colon (mucositis) in rats⁴⁴¹

L-glycine (Healthline)

Diminished liver and kidney injury caused by toxicants and drugs, including chemotherapy-induced liver injury, and protected stomach lining (gastric mucosa) against ulcers induced by chemicals or stress⁴⁴²

Off-label, Overlooked or Novel Cancer Approaches (ONCAs)

Group A: Good clinical evidence of efficacy

May be used in integrative protocols and programs

Therapy	Notes
Chronomodulated therapies	Reduced rate and severity of adverse reactions compared to those getting continuous infusion chemotherapy,⁴⁴³ including greatly reduced rate of severe damage to the intestinal lining (mucosal toxicity) and halved rate of functional impairment from peripheral sensitive neuropathy⁴⁴⁴ Reduced severe inflammation of the mouth and lips (stomatitis)⁴⁴⁵ Reduced rate and severity of adverse reactions while achieving higher rates of remissions (both complete and partial) compared to those getting continuous infusion chemotherapy⁴⁴⁶ Better quality life and less fatigue in metastatic colorectal cancer patients with normal 24-hour rest/activity rhythms than those with altered rhythms⁴⁴⁷ Patients' ability to tolerate the drug schedule varied from women to men⁴⁴⁸ Notable preclinical effects: Timing of cisplatin and carboplatin influenced whether male mice developed low counts of white blood cells (leukopenia ), bone marrow lesions and cortical tubular necrosis (death of tissue in the outer kidney)⁴⁴⁹
Metformin	Lower rate of grade 2 and 3 neuropathy, lower pain scores and lower markers of oxidative stress and heightened sensitivity to pain (hyperalgesia)⁴⁵⁰ Notable preclinical evidence Reduced loss of paw sensitivity and protected peripheral-nerve endings in mice⁴⁵¹ Prevented mental (cognitive) impairment due to the chemotherapy drug cisplatin⁴⁵² Requires a prescription from a licensed physician

Therapy

Notes

Chronomodulated therapies

Reduced rate and severity of adverse reactions compared to those getting continuous infusion chemotherapy,⁴⁴³ including greatly reduced rate of severe damage to the intestinal lining (mucosal toxicity) and halved rate of functional impairment from peripheral sensitive neuropathy⁴⁴⁴
Reduced severe inflammation of the mouth and lips (stomatitis)⁴⁴⁵
Reduced rate and severity of adverse reactions while achieving higher rates of remissions (both complete and partial) compared to those getting continuous infusion chemotherapy⁴⁴⁶
Better quality life and less fatigue in metastatic colorectal cancer patients with normal 24-hour rest/activity rhythms than those with altered rhythms⁴⁴⁷
Patients' ability to tolerate the drug schedule varied from women to men⁴⁴⁸
Notable preclinical effects:
- Timing of cisplatin and carboplatin influenced whether male mice developed low counts of white blood cells (leukopenia ), bone marrow lesions and cortical tubular necrosis (death of tissue in the outer kidney)⁴⁴⁹

Metformin

Lower rate of grade 2 and 3 neuropathy, lower pain scores and lower markers of oxidative stress and heightened sensitivity to pain (hyperalgesia)⁴⁵⁰
Notable preclinical evidence

Reduced loss of paw sensitivity and protected peripheral-nerve endings in mice⁴⁵¹
Prevented mental (cognitive) impairment due to the chemotherapy drug cisplatin⁴⁵²

Requires a prescription from a licensed physician

Group B: Limited clinical evidence of efficacy

May be used in integrative protocols and programs

Therapy	Notes
Aspirin (WebMD)	Reduced events related to vascular disease (abnormal condition of the blood vessels), including blood clots in deep veins (venous thromboembolism)⁴⁵³ Significan cautions regarding gastrointestinal bleeding and other risks with use; see Cautions on our Aspirin and Non-steroidal Anti-inflammatory Drugs page Used in the Block program⁴⁵⁴
Bisphosphonates (Cancer Research UK)	Zoledronic acid decreased bone pain and improved quality of life when combined with radiotherapy to treat painful bone metastases from colorectal and other cancers in a small study⁴⁵⁵ Note several side effects. Requires a prescription from a licensed physician
Cimetidine (Tagamet HB)	Reduced the suppression of immune function that typically follows surgical resection⁴⁵⁶ Notable preclinical evidence: reduced risk of kidney toxicity (nephrotoxicity) in mice without reducing the antitumor effects of cisplatin⁴⁵⁷ Note cautions and drug interactions: ask your doctor or pharmacist, or see the Cautions section of our Cimetidine page.
Statins	Use near the time of surgery may reduce anastomotic leaks (leaking where the colon segments were joined after removing the tumor) after elective colectomy⁴⁵⁸ Requires a prescription from a licensed physician Note cautions on our Statins page. Used in the Block program for colorectal cancer⁴⁵⁹

Diets and Metabolic Therapies

Mind-Body, Spiritual and Consciousness-changing Approaches

Manipulative and Body-Based Methods

Reducing Risk

Reducing the risk of developing cancer or the risk of recurrence

Risk Factors

Creating Healthy Habits: Lifestyle Associations

Group 1: Good clinical evidence of efficacy & safety, easy access

These therapies may be widely used in integrative cancer protocols and traditional medical systems.

Therapy	Notes
Calcium supplements (About Herbs) Evidence regarding calcium in your diet is listed above in Eating Well.	Decreased risk of colorectal cancer: The Continuous Update Project Expert Report considers the evidence for calcium in reducing risk to be strong.⁴⁷⁷ This conclusion is supported by a meta-analysis combining 15 studies⁴⁷⁸ even though some randomized controlled clinical trials following use for up to 11 years have failed to show a protective benefit.⁴⁷⁹
Magnesium supplements (About Herbs) Evidence regarding magnesium in your diet is listed above in Eating Well.	Reduced risk of colorectal cancer, especially colon cancer, with higher intake of magnesium from diet and/or supplements⁴⁸⁰
Medicinal mushrooms	Turkey tail mushrooms: PSK (an extract of turkey tail mushrooms) reduced recurrence of colorectal cancer when used with oral Tegafur/Uracil⁴⁸¹ Reishi mushrooms Suppressed development of colorectal adenomas in patients with prior adenomas.⁴⁸² Notable preclinical evidence: Inhibited proliferation of human colorectal cancer cells in mice⁴⁸³
Vitamin B supplements	Vitamin B₂ (WebMD): Reduced colorectal cancer risk⁴⁸⁴ Vitamin B₆ (About Herbs) Decreased risk of colorectal cancer with increased intake from diet and supplements⁴⁸⁵

Group 3: Limited clinical evidence of efficacy but good safety, used in leading integrative programs

Therapy	Notes
Combination therapies	Curcumin and quercetin Suppressed adenomas in patients with familial adenomatous polyposis (FAP), a risk factor for colorectal cancer⁴⁸⁶ Decreased polyp numbers and size⁴⁸⁷ Used in the Alschuler & Gazella complementary approaches⁴⁸⁸
Curcumin	Blocks or reduces risk of cancer development⁴⁸⁹ Reduced aberrant crypt foci (ACF) formation in smokers; ACF are one of the earliest changes that can be seen in the colon that may lead to cancer⁴⁹⁰ Notable preclinical evidence: Reduced cancer incidence in animal studies⁴⁹¹ Diminished aberrant crypt foci (ACF), intestinal polyps, and incidence and number of colon adenomas and adenocarcinomas in rodents⁴⁹² Reduced cancer stem cells and modulated communication between fibroblasts (connective tissue cells that make and secrete collagen proteins) in the tumor microenvironment and cancer stem cells⁴⁹³ Anticancer effects include inhibiting cell proliferation, invasion, migration, formation of blood vessels to supply tumors (angiogenesis) and metastasis; inducing cell cycle arrest and death (apoptosis)⁴⁹⁴ Used in these protocols and programs: Alschuler & Gazella complementary approaches⁴⁹⁵ Block program⁴⁹⁶ McKinney protocols⁴⁹⁷
Green tea extracts/EGCG The effects of drinking tea are discussed above in Eating Well.	Inhibited tumor stem cell proliferation, prevented tumor production, and reduced risk of recurrence after surgery⁴⁹⁸ Prevented the development and progression of precancerous lesions, such as colorectal adenomas,⁴⁹⁹ and reduced incidence of metachronous (not concurrent) adenomas after colorectal adenomas were removed⁵⁰⁰ Notable preclinical evidence: Protected animals from colon cancer induced by azoxymethane⁵⁰¹ Inhibited polyp formation in animals and suppressed small intestinal tumor formation in mice⁵⁰² Inhibited tumor incidence, with near-normal survival rate and restoration of normal colon architecture in rodents⁵⁰³ Inhibited pre-cancerous polyps and development of colon cancer in mice fed a high-fat diet⁵⁰⁴ Inhibited cancer development in intestinal, colon and gastric cancer in preclinical studies⁵⁰⁵ Used in these Programs and Protocols: Alschuler & Gazella complementary approaches⁵⁰⁶ Block program⁵⁰⁷ Lemole, Mehta & McKee protocols⁵⁰⁸
Multivitamin supplements	Might decrease the risk of colorectal cancer,⁵⁰⁹ although use was not related to colorectal cancer risk in a large study of US women aged 45 years or more.⁵¹⁰ Used in the Block program⁵¹¹
Omega-3 fatty acid supplements The effects of omega-3s in your diet are discussed above in Eating Well.	Decreased risk of colon cancer with fish oil supplements,⁵¹² especially in men, but an increased risk was found with individuals with high genetic risk⁵¹³ Reduced number and size of rectal adenomas⁵¹⁴ Reduced risk of colon cancer with consumption of omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) and an omega-6/omega-3 ratio of 2-4:1⁵¹⁵ EPA alone: Reduced number and size of polyps in patients with familial adenomatous polyposis with eicosapentaenoic acid (EPA) alone⁵¹⁶ No reduction in the proportion of patients with at least one colorectal adenoma in patients with sporadic colorectal neoplasia, used either with or without aspirin, compared with a placebo⁵¹⁷ Used in these programs and protocols: Block program⁵¹⁸ Lemole, Mehta & McKee protocols⁵¹⁹ McKinney protocols⁵²⁰
Probiotics	Preliminary but mixed evidence that probiotic therapy may decrease the risk of developing colorectal cancer⁵²¹ with different effects from different species⁵²² As reported above in Eating Well, yogurt consumption reduced risk of conventional colorectal adenoma, especially adenomas with high malignant potential, in men. Probiotics in yogurt are thought to contribute to this effect.⁵²³ Notable preclinical evidence: protected mice against colorectal cancer development with Lactobacillus casei BL23⁵²⁴ and histidine decarboxylase (HDC) Lactobacillus reuteri⁵²⁵ Used in these programs and protocols: Block program⁵²⁶ McKinney protocols⁵²⁷
Resveratrol	Inhibited a major risk factor for colon cancer development in normal linings of the colon (colonic mucosa) but did not inhibit colon cancer in a small study of colon cancer patients⁵²⁸ Used in these programs and protocols: Alschuler & Gazella complementary approaches⁵²⁹ Block program⁵³⁰
Vitamin D	Blood levels: Increased risk of cancer with poor vitamin D status⁵³¹ Lower risk of colorectal adenomas and recurrent adenomas with higher circulating 25(OH)D levels;⁵³² the impact of vitamin D status is related to calcium intake⁵³³ Supplement use: Lower risk of colorectal cancer with increased intake of vitamin D, both through diet and with supplements⁵³⁴ Lower risk of incidence and recurrence of colorectal adenomas with vitamin D intake; combined calcium and vitamin D supplementation reduced risk of colorectal cancer recurrence,⁵³⁵ but no conclusive evidence that use of supplements alone reduces risk.⁵³⁶ In one study, estrogen therapy interacted with this benefit, showing benefit only in women not undergoing estrogen therapy.⁵³⁷ Research in animals shows that supplementation increases 25(OH)D levels,⁵³⁸ but no conclusive evidence shows that use of supplements reduces risk in humans.⁵³⁹ Used in the Alschuler & Gazella complementary approaches⁵⁴⁰
Vitamin E supplements	Serum levels: Patients with colorectal cancer showed lower concentrations of serum vitamin E compared with hospital-based controls in a meta-analysis.⁵⁴¹ Supplement use: The specific tocopherols within supplements may have different effects. Most supplements contain α-tocopherol, while a γ-tocopherol-rich mixture of tocopherols inhibits growth of colon and other types of tumors in animals⁵⁴² and in epidemiological studies⁵⁴³ Reduced risk of colorectal cancer in women taking unspecified forms of vitamin E supplements⁵⁴⁴ but not in men taking 400 IU/day of all-rac-α-tocopheryl acetate (see the study for an analysis of whether the correct form was used)⁵⁴⁵ in large studies Other reviews and a meta-analysis concluded no reduced risk with vitamin E or other antioxidants⁵⁴⁶ (but again, the specific forms of vitamin E may have varying effects). No reduced risk of adenoma occurrence⁵⁴⁷ Used in these programs and protocols: Lemole, Mehta & McKee protocols,⁵⁴⁸ using mixed tocopherols and tocotrienols McKinney protocols,⁵⁴⁹ using mixed tocopherols with gamma and delta forms

Group 4: Potential significant benefit, but either limited clinical evidence of efficacy or significant cautions

May be used in leading integrative oncology programs. Therapies in this group may need more medical oversight and surveillance.

Therapy	Notes
Fermented wheat germ extract	Reduced likelihood of colorectal cancer recurrence and new metastatic disease occurrence⁵⁵⁰
Selenium	Decreased colon cancer risk with elevated selenium intake in observational studies⁵⁵¹ . but only a marginal decrease in a clinical trial; biggest effects were seen in males and in former smokers. Benefit was seen only for those with lower plasma selenium concentrations before supplementation⁵⁵²

Group 5: Especially promising preclinical or emerging clinical evidence of efficacy and safety

Other therapies with preclinical evidence only for reducing risk

Expand list

Therapy	Notes
Astragalus and other saponins	Prevented gastrointestinal lesions in animals from progressing into cancer⁵⁵³
Combinations of therapies	Resveratrol and grape seed extract: Suppressed tumor incidence in mice similar to sulindac (a nonsteroidal anti-inflammatory drug, see below) without any gastrointestinal toxicity⁵⁵⁴
Ginger The effects of ginger in your diet are discussed above in Eating Well.	Reduced early markers in the development of colorectal canceramong healthy adults⁵⁵⁵ Anticancer effects (antitumor, reduced proliferation, reduced invasion) in preclinical studies, with limited clinical evidence⁵⁵⁶ Nanoparticles derived from edible ginger prevented cancer associated with colitis in animal studies.⁵⁵⁷
Grape seed extract	Inhibited cancer proliferation and enhanced cell death (apoptosis) to prevent cancer development in animals⁵⁵⁸ Prevented a pre-cancerous condition (aberrant crypt foci) induced by chemicals in rats⁵⁵⁹ Decreased formation, total number and size of adenomatous polyps in mice⁵⁶⁰

Group 6: Evidence of no efficacy or may be dangerous

Therapy	Notes
Aged garlic extract (CAM Cancer) The effects of garlic in your diet are discussed above in Eating Well.	Elevated risk of colorectal cancer with garlic pills⁵⁶¹
Beta-carotene supplements (About Herbs) The effects of foods containing beta-carotene are discussed above in Eating Well.	Increased risk of colorectal adenoma and overall mortality in the general population⁵⁶²
Folic acid (About Herbs)	No convincing evidence of reduced risk of colorectal cancer or adenomas in average-risk or high-risk populations; one randomized controlled trial found an increase in advanced adenomas with use⁵⁶³

Therapy

Notes

Aged garlic extract (CAM Cancer)

The effects of garlic in your diet are discussed above in Eating Well.

Elevated risk of colorectal cancer with garlic pills⁵⁶¹

Beta-carotene supplements (About Herbs)

The effects of foods containing beta-carotene are discussed above in Eating Well.

Increased risk of colorectal adenoma and overall mortality in the general population⁵⁶²

Folic acid (About Herbs)

No convincing evidence of reduced risk of colorectal cancer or adenomas in average-risk or high-risk populations; one randomized controlled trial found an increase in advanced adenomas with use⁵⁶³

Off-label, Overlooked or Novel Cancer Approaches (ONCAs)

Group A: Good clinical evidence of efficacy

May be used in integrative protocols and programs

Therapy	Notes
Aspirin	Recommended by the US Preventive Services Task Force for primary prevention of colorectal cancer⁵⁶⁴ Reduced risk of colorectal cancer⁵⁶⁵ including in people with hereditary colorectal cancer (Lynch syndrome)⁵⁶⁶ Prevented or reduced colorectal adenoma recurrence⁵⁶⁷ May reduce recurrence of adenomas and incidence of advanced adenomas in individuals with an increased risk of colorectal cancer⁵⁶⁸ Risk reduction may depend on dose, and may interact with height, weight and age of the individual;⁵⁶⁹ no reduced risk was seen among individuals aged 65 years or older,⁵⁷⁰ while another study found reduced risk in those over 70 only if use was initiated when younger⁵⁷¹ Notable preclinical evidence: Reversed or inhibited the activity of platelets to promote cancer cell proliferation and metastasis⁵⁷² Reduced cancer cell proliferation through the modulation of an oncoprotein in cell lines⁵⁷³ Note cautions about bleeding: ask your doctor or pharmacist or see the Cautions section of our Aspirin and Other Non-steroidal Anti-inflammatory Drugs (NSAIDs) page Used in these programs and protocols: Block program⁵⁷⁴ Chang strategies⁵⁷⁵
Bisphosphonates (Cancer Research UK)	Modestly reduced risk of colorectal cancer⁵⁷⁶ Note several side effects. Requires a prescription from a licensed physician
Metformin	Reduced risk with use in some but not all analyses,⁵⁷⁷ including in those with type 2 diabetes⁵⁷⁸ Decreased risk of colorectal adenoma recurrence⁵⁷⁹ and reduced aberrant crypt foci (a pre-cancerous condition) in patients at high risk of adenoma recurrence⁵⁸⁰ Prevented metachronous (not concurrent) colorectal adenomas or polyps⁵⁸¹ Requires a prescription from a licensed physician Used in the Block program⁵⁸²
Nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin (MedicineNet)	General NSAIDs other than aspirin: Reduced risk of colorectal cancer⁵⁸³ especially of distal colon cancer, at higher doses, in women and in Caucasians⁵⁸⁴ Celecoxib and other COX-2 inhibitors: Lower adenoma recurrence in those with a history of previous adenoma, but with increased risk of cardiovascular events⁵⁸⁵ Lower colorectal cancer risk in high-risk populations (those with familial adenomatous polyposis [FAP], Lynch syndrome or mutations that involve DNA repair pathways), but with increased risk of cardiovascular events⁵⁸⁶ Reduced number of colorectal polyps in young adults with familial adenomatous polyposis⁵⁸⁷ Sulindac: Decreased number of polyps and their diameter in patients with familial adenomatous polyposis (FAP)⁵⁸⁸ Lower colorectal cancer risk in high-risk populations (those with familial adenomatous polyposis [FAP], Lynch syndrome or mutations that involve pathways of DNA repair), but with increased risk of cardiovascular events⁵⁸⁹ Decreased risk when used with difluoromethylornithine (DFMO), without a significant increase in adverse events⁵⁹⁰ Risks of serious side effects (especially gastrointestinal and cardiovascular) must be considered against potential benefits;.⁵⁹¹ see Cautions on our Aspirin and Non-steroidal Anti-inflammatory Drugs page May require a prescription from a licensed physician
Thiazolidinediones (TZDs) (Diabetes.co.uk) Examples include pioglitazone (Actos) and rosiglitazone (Avandia)	Modestly reduced risk of colorectal cancer⁵⁹² Requires a prescription from a licensed physician

Group B: Limited clinical evidence of efficacy

May be used in integrative protocols and programs

Therapy	Notes
Artesunate	Reduced disease recurrence when used at the time of surgery in a small trial⁵⁹³ Note cautions on our Artemisinin and Artesunate page.
Statins	Reduced risk of colorectal cancer in large epidemiological studies, but not always in randomized controlled studies, case control and cohort studies, perhaps because of shorter timeframes and confounding conditions, or perhaps because of publication bias in epidemiological studies⁵⁹⁴ Mixed evidence regarding reduced risk of recurrent, multiple or advanced adenomas or adenomatous polyps⁵⁹⁵ Reduced risk for patients with diabetes or irritable bowel disease (IBD) with long-term use⁵⁹⁶ Noteworthy preclinical evidence: Reduced colorectal cancer development in mice⁵⁹⁷ Requires a prescription from a licensed physician Note cautions on our Statins page. Used in the Chang strategies⁵⁹⁸ in a "cocktail" treatment for preventing cancer occurrence as well as recurrence, especially for colon cancer

Therapy

Notes

Artesunate

Reduced disease recurrence when used at the time of surgery in a small trial⁵⁹³
Note cautions on our Artemisinin and Artesunate page.

Statins

Reduced risk of colorectal cancer in large epidemiological studies, but not always in randomized controlled studies, case control and cohort studies, perhaps because of shorter timeframes and confounding conditions, or perhaps because of publication bias in epidemiological studies⁵⁹⁴
Mixed evidence regarding reduced risk of recurrent, multiple or advanced adenomas or adenomatous polyps⁵⁹⁵
Reduced risk for patients with diabetes or irritable bowel disease (IBD) with long-term use⁵⁹⁶
Noteworthy preclinical evidence:
- Reduced colorectal cancer development in mice⁵⁹⁷
Requires a prescription from a licensed physician
Note cautions on our Statins page.
Used in the Chang strategies⁵⁹⁸ in a "cocktail" treatment for preventing cancer occurrence as well as recurrence, especially for colon cancer

Optimizing Your Terrain

Cytokines, Inflammation and Outcomes

Cytokines are proteins with a complex relationship to your immune system and sleep cycles. If your circadian rhythm is disrupted by an external change in the light-dark cycle—such as by night-shift work or staying awake late at night—your immune cells produce a heightened inflammatory response driven in part by cytokine release.⁵⁹⁹

Creating an environment within your body that does not support cancer development, growth or spread

See Body Terrain and the Tumor Microenvironment.

Natural Products

Therapy	Notes
Garlic cupplements, including aged garlic extract (CAM Cancer) The effects of garlic in your diet are discussed above in Eating Well.	Increased immune function (the number and activity of natural killer cells) in those with advanced inoperable colon cancer.⁶⁰¹ Reduced blood coagulation⁶⁰² Modest reduction in blood pressure in patients with mild hypertension with a garlic powder preparation⁶⁰³ Managed blood glucose⁶⁰⁴ Caution regarding increased risk of colorectal cancer with use Used in the Block program⁶⁰⁵ for coagulation
Astragalus and other saponins	Anti-inflammatory⁶⁰⁶ Immune support or modulation⁶⁰⁷ Antioxidant⁶⁰⁸
Combinations of therapies	Couplet medicines (Astragalus membranaceus and Jiaozhen) Anti-inflammatory⁶⁰⁹ Daikenchuto (ginger, ginseng, and Zanthoxylum fruit) Suppressed postoperative inflammation following surgery for colorectal cancer⁶¹⁰ Quxie Capsule (a combination of traditional Chinese medicine therapies): Immune modulation⁶¹¹
Curcumin	Anti-inflammatory and antioxidant,⁶¹² including greater elevation in enzymes and activity that reduce systemic oxidative stress in patients with solid tumors receiving standard chemotherapy regimens⁶¹³ Decreased serum levels of TNF-α, a protein that may boost immune response and may also cause death of some types of tumor cells⁶¹⁴ Effects on gene expression and signaling pathways⁶¹⁵ The Meriva formulation decreased oxidative stress and systemic inflammation in patients with solid tumors undergoing chemotherapy.⁶¹⁶ Normalized and diversified the colon microbiota, reducing inflammation in the colon and preventing colon cancer in mice⁶¹⁷ Used in these protocols and programs: Alschuler & Gazella complementary approaches⁶¹⁸ Block program⁶¹⁹
Fermented wheat germ extract	Favorably impacted immune response⁶²⁰ and enhanced immune activity in animal studies⁶²¹
Ginger	Antioxidant effects in preclinical studies⁶²² Anti-inflammatory effects in preclinical studies, with limited clinical evidence;⁶²³ . nanoparticles derived from edible ginger showed anti-inflammatory properties in animal studies.⁶²⁴ Improved intestinal barrier function⁶²⁵ Inhibits enzyme action and may impact the microbiome⁶²⁶ Alters cell signaling pathways⁶²⁷ Regulates genes that promote cell death (apoptosis)⁶²⁸ Used in these programs and protocols to reduce inflammation: Alschuler & Gazella complementary approaches⁶²⁹ Block program⁶³⁰ McKinney protocols⁶³¹
L-glutamine, also known as glutamine	Decreased inflammation among patients with prostate or rectal cancer receiving radiation therapy⁶³² or combination radiation and chemotherapy⁶³³ Improved nitrogen balance and boosted immune system response⁶³⁴ An oral nutrition supplement enriched with carbohydrates, glutamine and antioxidants before surgery somewhat weakened but did not prevent peripheral insulin resistance following surgery.⁶³⁵ Balanced glucose-insulin homeostasis and facilitated recovery in patients undergoing colon cancer resection.⁶³⁶ Reduced the usual decrease in branched-chain amino acids (BCAA, a group of three essential amino acids) after surgery with glutamine-enriched total parenteral nutrition (TPN)⁶³⁷
Grape seed extract	Supports healthy coagulation by inhibiting clotting processes that protect tumor cells and facilitate metastasis⁶³⁸ Anti-inflammatory,⁶³⁹ including reduced inflammation in mice⁶⁴⁰ Antioxidant⁶⁴¹ Used in the Block program⁶⁴² for hypercoagulation (excessive blood clotting)
Green tea extracts/EGCG The effects of drinking tea are discussed above in Eating Well.	Antioxidant⁶⁴³ Anti-inflammatory⁶⁴⁴ Antimutagenic (counteracts the effects of mutagens, which cause genetic mutations) and anticarcinogenic⁶⁴⁵ including reduced instability in chromosomes in noncancerous colon cells⁶⁴⁶ Inhibited VEGF (a substance made by cells that stimulates new blood vessel formation) and other growth factors⁶⁴⁷ Reduced fasting blood glucose in some studies and meta-analyses,⁶⁴⁸ but not all⁶⁴⁹ Used in these programs and protocols: Alschuler & Gazella complementary approaches⁶⁵⁰ for inflammation, insulin function/blood sugar regulation and oxidation; used specifically with colorectal cancer Block program⁶⁵¹ for inflammation, insulin function/blood sugar regulation specifically with colorectal cancer McKinney protocols⁶⁵² for inflammation, insulin function/blood sugar regulation
L-carnosine (WebMD)	Antioxidant and anti-inflammatory⁶⁵³
L-glycine (Healthline)	Anti-inflammatory, immunomodulatory and protective of cells (cytoprotective)⁶⁵⁴
Omega-3 fatty acids The effects of omega-3s in your diet are discussed above in Eating Well.	Reduced inflammation,⁶⁵⁵ or improved anti-inflammatory markers⁶⁵⁶ including when accompanying anticancer treatment⁶⁵⁷ and in patients undergoing radical colorectal cancer resection⁶⁵⁸
Probiotics	Improved immune response⁶⁵⁹ Improved intestinal microbial environment⁶⁶⁰
Turkey tail mushrooms or extracts	Inhibited processes that prevent the immune system from recognizing and responding to the cancer in people with gastrointestinal cancer⁶⁶¹ Positive immune impacts in patients with gastrointestinal cancer⁶⁶²
Vitamin C	Low plasma AA concentration is associated with high levels of an inflammatory marker (C-reactive protein)⁶⁶³
Vitamin E supplements	Improved immune activity in patients with advanced colorectal cancer⁶⁶⁴

Off-label, Overlooked or Novel Cancer Approaches (ONCAs)

Therapy	Notes
Aspirin	Anti-inflammatory⁶⁶⁵ Significan cautions regarding gastrointestinal bleeding and other risks with use; see Cautions on our Aspirin and Non-steroidal Anti-inflammatory Drugs page Used in the Block program⁶⁶⁶ for inflammation
Bisphosphonates (Cancer Research UK) (Clodronate liposomes)	Increased immune biomarkers in mice⁶⁶⁷ Increased gut bacteria associated with reduced colorectal cancer risk in mice⁶⁶⁸
Cimetidine (Tagamet HB)	Immune and immunomodulatory effects,⁶⁶⁹ including a more rapid return to pre-operative immune function after surgery⁶⁷⁰ Reduced adhesion, a process that facilitates metastasis⁶⁷¹ Note cautions and drug interactions: ask your doctor or pharmacist. Used in these protocols and programs: Block program⁶⁷² for immunity Lemole, Mehta & McKee protocols⁶⁷³ for immunomodulation
Copper chelation with tetrathiomolybdate (TM) and other substances	Anti-inflammatory⁶⁷⁴ Improved immune pathway response in animals⁶⁷⁵
Metformin	Anti-inflammatory⁶⁷⁶ Reduced blood glucose (glycemia);⁶⁷⁷ elevated levels are a risk factor for colorectal cancer⁶⁷⁸ and are associated with poorer survival in some reports⁶⁷⁹ Requires a prescription from a licensed physician Used in these protocols and programs for glycemia Block program⁶⁸⁰ McKinney protocols,⁶⁸¹ with care to monitor vitamin B₁₂ status
Nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin	Anti-inflammatory⁶⁸² Risks of serious side effects (especially gastrointestinal and cardiovascular) must be considered against potential benefits;.⁶⁸³ see Cautions on our Aspirin and Non-steroidal Anti-inflammatory Drugs page May require a prescription from a licensed physician
Rapamycin (sirolimus)	Metabolic response with short-course radiotherapy in rectal cancer patients⁶⁸⁴ Requires a prescription from a licensed physician
Statins	Anti-inflammatory⁶⁸⁵ Note cautions on our Statins page. Requires a prescription from a licensed physician Used in the Block program⁶⁸⁶ for inflammation

Other Therapies

Acupuncture and Electroacupuncture

Short-term fasting

Antibiotic Use and Colorectal Cancer

Antibiotics can dramatically alter your microbiome. More frequent or oral antibiotic use was linked to a 17% increased risk of colon cancer but a reduced risk of rectal cancer (mostly among women) in a very large observational study.⁶⁹² In a separate very large study, the increased risk was evident even with minimal use or with use 10 or more years prior to diagnosis, and risk was strongest with antibiotics with anti-anaerobic effects.⁶⁹³

“When asked about the difference between the apparent impact of antibiotic use on the risk of cancer in the colon when compared to the rectum, [senior author Cynthia] Sears commented, ‘We think these differences highlight the differences in biology and likely the microbiome between these two cancer sites. Hence we hypothesize that antibiotics impact disease at these sites differently.’”⁶⁹⁴

We know that lifestyle factors and your gut microbiome interact to influence the development and progression of colorectal cancer. We are not yet clear on exactly how this plays out in people or what we can do to manipulate the microbiome favorably. We know that diet influences the microbial community in the gut. Researchers think the interaction between diet and gut microbiota influences colorectal cancer development by changing your metabolism and immune system.⁶⁹⁵ Evidence supports these assertions:

A high-fat diet is bad news for gut health, as it produces secondary bile acids. These acids change the microbiome, resulting in increased oxidation and inflammation that damage colon cells.⁶⁹⁶
Beneficial bacteria in the gut are needed to process and create essential nutrients by fermenting dietary fiber and producing butyrate. These microbial processes provide energy to colon cells and promote protective immune system effects. Adequate dietary fiber is thus essential for a healthy interplay between the gut microbiome, colon cells and immunity.⁶⁹⁷ Lower levels of butyrate-producing bacteria are associated with the presence of colorectal cancer.⁶⁹⁸
Impacts of a healthy microbiome with colorectal cancer include these:⁶⁹⁹
A healthy gut microbiome appears to support the anticancer action of the chemotherapy drug oxaliplatin.
Bacteria in the genus Bifidobacterium are crucial to optimizing the anticancer action of ligand 1 drugs (PD 1 checkpoint inhibitors), which activate the immune system to attack tumors.
Gut microbes can prevent reactivation of drug metabolites that can damage the intestines and cause diarrhea related to drugs such as camptothecin.
Microbial species in the intestines can impact inflammation.

People with colorectal cancer have less diverse gut bacteria, with reduced levels of Bifidobacterium, Clostridium, Faecalibacterium and Roseburia, for instance. Harmful species including Escherichia coli, E. faecalis, F. nucleatum, and Streptococcus gallolyticus also tend to be present in colorectal cancer patients.⁷⁰⁰ For example, enterotoxigenic Bacteroides fragilis [ETBF], which produces toxins in the digestive tract, is associated with a greater number of early-stage carcinogenic lesions and increased risk of colorectal cancer.⁷⁰¹

Probiotics, Prebiotics and Synbiotics

Probiotics are living microorganisms (bacteria and some yeasts) that can provide health benefits that go beyond basic nutrition, such as supporting gut and immune health and keeping the gut microbiota in balance. Examples of probiotic foods are yogurt, kefir, sauerkraut, tempeh and kimchi. Probiotics must be consumed in sufficient numbers to be effective.

Prebiotics are dietary fibers that feed the friendly bacteria in your gut. Most prebiotics are soluble fiber substances like inulin, found in foods like bananas, onions, jerusalem artichokes, jicama, garlic and others, plus chicory root. Your helpful bacteria turn inulin and other fibers into energy for the colon cells and create protective immunity. Inulin is increasingly being added to a number of processed foods and probiotic supplements.

Synbiotics contain prebiotics and probiotics together.

Use of pre- and probiotics can reduce some symptoms and side effects of cancer treatments and can improve the gut microbiome and impact inflammation as described above.

See our Probiotics summary for more information.

Surgery and Colorectal Cancer

Key Points: Surgery and Colorectal Cancer

Surgery as a treatment for colorectal cancer can greatly improve the prognosis but can involve several complications that can reduce CRC survival and increase the risk of recurrence.
Some factors that increase the risk of surgical complications are under the control or influence of the surgical team and/or the patient. Others, such as age, gender or prior abdominal surgery, are not.
Numerous negative consequences of surgical complications are possible, so a proactive approach to prevent them is important.
Prehabilitation and/or enhanced recovery after surgery (ERAS) programs and interventions are designed to prevent or lessen the complications of surgery.

Colorectal cancer treatment often includes surgery. The surgery may provide long-term benefit regarding cancer outcomes, but risks and complications are also relatively commonplace. We provide a brief overview of issues and integrative approaches surrounding colorectal cancer surgery. General information about surgery with cancer is available on our Integrative Approaches to Surgery page.

Clinical Practice Guidelines

For Healthcare Professionals: Enhanced Recovery after Surgery (ERAS)

ERAS is an approach focusing on counselling before surgery, optimizing nutrition, standardizing approaches to pain relief and getting you (the patient) moving and on your feet following surgery. It draws from several modalities, such as nutrition, medication, movement and counseling.⁷⁰²

Guidelines for patients from the Enhanced Recovery After Surgery (ERAS®) Society:⁷⁰⁷

Recommendations before hospital admission:
- Stop smoking at least four weeks before surgery to reduce problems with breathing and wound healing
- Engage in a prehab activity program (see below) to promote quicker recovery of function and fewer complications, especially if you are less fit
Recommendations before surgery:
- Avoid sedatives such as benzodiazepines if possible; taper a withdrawal if needed.⁷⁰⁸ Also, see Integrative Approaches and Surgery for a list of supplements to stop taking before surgery.
Recommendations following surgery:
- When you are allowed to eat, choose healthier foods from the menu. See Integrative Approaches and Surgery for examples of healthy eating when recovering from surgery.
- If prescribed, use oral nutritional supplements from the day of surgery or as directed by your doctor.
- Move as much as comfortable, including getting on your feet as soon as you can.

The American Society of Colon and Rectal Surgeons and Society of American Gastrointestinal and Endoscopic Surgeons provide guidelines for the surgical team: Clinical practice guidelines for enhanced recovery after colon and rectal surgery from the American Society of Colon and Rectal Surgeons and Society of American Gastrointestinal and Endoscopic Surgeons.⁷⁰⁹

Prehab and Surgical Outcomes

Prehabilitation (prehab), “the process of enhancing physical fitness before an operation to enable the patient to withstand the stress of surgery,” can reduce several risk factors for surgical complications, including malnutrition, anxiety and depression, and may also help to manage uncontrolled conditions or comorbidities, including glycemia, diabetes, hypertension and anemia.⁷¹⁰

Surgical Factors Associated with Increased Recurrence Risk

Even though surgery is a routine treatment for solid tumors, surgery itself can promote the development of metastasis by releasing tumor cells into circulation, suppressing important immune defenses such as your cellular immune system and and promoting the development of blood vessels to supply tumors (angiogenesis).⁷¹²

Type of Surgery: Open or Laparoscopic

The type of surgery—whether open surgery or laparoscopic surgery—has a great impact on the resulting inflammation—greater than the choice of anesthetic and pain management techniques (epidural versus intravenous analgesia).

Surgical Conditions

Mild low body temperature (hypothermia) worsens the suppression of your immune response from abdominal surgery.⁷¹⁶ Hypothermia may impair your immune system’s ability to stop infection and kill cancer cells. Maintaining your body temperature during surgery will reduce your risk of immune suppression.

Use of blood transfusion products can cause suppression of your immune response and increase your risk of recurrence.⁷¹⁷ Blood transfusion using your own blood (autologous transfusion) may reduce your risk of recurrence.⁷¹⁸

Patient Condition at the Time of Surgery

Your stress level and other characteristics around the time of surgery can affect your immune system and may increase your risk of recurrence:

Show list

Reducing Factors around the Time of Surgery that Increase Recurrence Risk

Delaying Surgery and Survival

Delaying surgery may lead to poorer survival, according to a systematic review. Conclusions from the review:⁷²³

With primarily resected colon cancer, delays of more than 30 to 40 days are associated with lower survival.
With rectal cancer, performing surgery more than seven to eight weeks following neoadjuvant therapy (therapy prior to surgery) was associated with decreased survival.

Combined use of the beta blocker propranolol and the anti-inflammatory etodolac for five days before surgery has been used safely to reduce metastases and mortality. However, this combination may not be safe in patients with asthma, cardiovascular disease, diabetes, bleeding risk, GI ulcers or low blood pressure.⁷²⁴

Taking precautions to prevent blood clots, neutrophil extracellular traps (NETs) and low oxygen levels (hypoxia) may reduce recurrence after surgery.⁷²⁵

See these pages for suggestions for managing stress or anxiety before and after surgery:

Surgical Complications and Infections

Surgical Complications

Colorectal cancer surgery can involve several possible complications:⁷²⁶

During surgery:

Show list

After surgery:

Show list

Infections and complications of surgery not only make recovery more difficult, they may impact your cancer outcomes and even your survival (see sidebar).⁷²⁷

Colorectal surgery is invasive and disrupts the equilibrium of your gut microbiome—the microbes in your gut. A microbial imbalance can impair the function of your local immune response, promote systemic inflammation, and potentially lead to infection following surgery.⁷²⁸ Perhaps due to the large number of bacteria present in the colon and rectum, the number of surgical site infections in patients undergoing colorectal surgery is high—up to 26 percent.

Complications can reduce survival through several routes:

Show list

Factors Increasing Risk of Infection and Other Complications

Can Be Influenced or Controlled	Cannot Be Influenced
Obesity^a Smoking^a Nutritional status^b Uncontrolled conditions or comorbidities, including glycemia, diabetes, hypertension and anemia^a Type of surgery, whether open or laparoscopic, plus how complications caused by surgery and treatment (such as nicking the bladder) are handled, choice of instruments, management of blood loss in surgery, prophylactic draining, creating a protective stoma and operating time Choice of pain control and diet following surgery Choice of surgeon and hospital/clinic^c Anxiety and depression present before surgery^d Inflammation or compromised immunity^a Chemoradiotherapy before surgery^e Mechanical bowel preparation before surgery^g Low muscle mass or density before surgery^h	Age (65 or older)^a Gender Prior abdominal surgery Adhesions (scar-like tissues that adhere together)
	Factors Not Increasing Risk
	Radiotherapy before surgery^e

Obesity, smoking, glycemia, hypertension, diabetes, anemia-compromised immunity or inflammation, and patient age 65 or older are each linked to increased wound complications following surgery.⁷³² In elective surgery in overweight patients, weight loss before surgery is recommended, as is correction of anemia with iron, vitamin B₁₂ and folate supplementation as needed, such as for pernicious anemia.⁷³³
Malnutrition is linked to a greater chance of surgical complications, longer hospital stay, less tolerance of other cancer treatments, higher risk of death and higher health-care costs.⁷³⁴
Surgeons with more experience as well as hospitals with higher numbers of colorectal surgery patients are associated with fewer complications and, in some studies, lower risk of recurrence and higher survival.⁷³⁵
Anxiety and depression before surgery negatively affect wound healing, your risks of infection and a longer hospital stay, and your ability to adhere to your medical treatment plan.⁷³⁶
A 2016 meta-analysis found that radiation therapy before radical rectal cancer surgery didn’t increase risk of wound complications.⁷³⁷ However, some evidence shows increased risk of infection and other complications such as anastomotic leakage with chemoradiotherapy before surgery.⁷³⁸
Men are at higher risk than women of anastomotic leaks with rectal cancer surgery.⁷³⁹
The current standard to reduce infection risk is called mechanical bowel preparation (MBP, giving oral medicine to clear feces from the intestines) plus prophylactic antibiotics. Some research has suggested that MBP doesn’t improve infection outcomes and may cause greater harm because it is often poorly tolerated.⁷⁴⁰
Low skeletal muscle mass and density were associated with longer hospital stays and higher risks of postsurgical complications, and both short-term and long-term mortality.⁷⁴¹

Preventing Surgical Complications

Reducing the risk of complications: what you and your surgeon can do

Anastomotic Leaks

Anastomotic leaks—occurring at the place where colon sections are joined after a section is removed— can lead to other problems such as longer hospital stays; higher risks of readmission, reoperations or mortality; and a worse quality of life. Patients who have anastomotic leaks following cancer operations also have a higher risk of distant recurrence and long delays in receiving indicated adjuvant (supplemental) chemotherapy.

Recognized or proposed risk factors include these (also see the discussion below of pain control and surgical outcomes):⁷⁴²

Show list

Interventions for the surgical team to reduce the incidence of anastomotic leaks:⁷⁴³

Show list

Interventions for patients:

Stop smoking in the period surrounding surgery

What You Can Do

First, find out how much time you can take before surgery to develop a plan and prepare for surgery.
Preparing your body
- Discuss which risk factors you can improve before surgery and come up with a plan of actions to take. Actions may include controlling hypertension, stress, hyperglycemia and other conditions, or stopping smoking
- Consider incorporating stress management practices in the weeks leading up to surgery. Many patients find imagery practices specific to preparing for surgery to be helpful. See Managing Stress, Stress, Mind-Body Approaches and Guided Imagery.
- In addition to effective stress management practices, use emotional support, counselling and pre-surgery medication as appropriate to help reduce preoperative psychological stress.
- If you typically clean an animal litter box or bird cage, find someone else to clean it before and for several weeks after your surgery.
Optimizing your surgical context:
- Check postoperative infection rates for the hospital where your surgery will be performed at Medicare.gov—Hospital Compare. While individual surgeon complication rates are available for many types of surgery, they are not published for breast surgery. Having said that, infection rates tend to be higher on average with less-experienced surgeons (a pretty good rule of thumb for having good experience is to consider surgeons who have done at least four per month of your specific type of surgery for five years).
- Inform your surgical team of any supplements, herbs or other therapies you’re using prior to surgery.
- If you have financial or social barriers to good pre- and postsurgical care, ask to be referred to an oncology social worker or oncology navigator for assistance.
- Schedule your surgery as an ambulatory procedure rather than as an inpatient hospital stay, if possible.
- Discuss your options for anesthesia, post-surgical pain control (see more about ERAS protocols above) and the steps in the column at right with your surgical team at the pre-op visit.
Immediately before surgery:
- Avoid presurgical dehydration.
- See if you can postpone surgery if you develop a cold, flu, pneumonia or other infection shortly before scheduled surgery.
After surgery
- Before leaving the hospital, be sure you (and anyone who will be assisting you at home) fully understand and follow all wound care instructions carefully. Call your physician immediately if you show any signs of infection—an increase of redness, swelling, pain or discharge from your wound.
- Avoid contact with soil for two or more weeks after surgery.
- Consult an integrative physician or licensed naturopath (preferably one who is certified in oncology) to recommend approaches to maintain healthy immune function to improve your wound healing and reduce your risk of infection.
- In the weeks following your surgery, if you need a medical procedure that may introduce bacteria to the body, check with your surgeon about using antibiotics to prevent infection.

What Your Surgeon Can Do

HA/CMC film adhesion barrier: A hyaluronic acid/carboxymethylcellulose (HA/CMC) film adhesion barrier can reduce adhesion formation, but a multicenter study found its use increased the risk of total adverse events and serious adverse events including excess body heat (hyperthermia), abscess in the pelvic area or incision site, urinary tract infection, urinary retention and ileus (bowel or intestinal blockage or paralysis).⁷⁴⁵

Infection and Treatment Outcomes

Infection may delay cancer treatments such as chemotherapy or radiation, leading to less effective treatment and worse outcomes, including recurrence.⁷⁴⁶

Some evidence shows that radiochemotherapy before surgery for rectal cancer may increase risk of infection and other complications such as anastomotic leakage.⁷⁴⁷ However, a 2016 meta-analysis found that radiation therapy alone before radical rectal cancer surgery didn’t increase risk of short-term wound complications,⁷⁴⁸ although side effects and a decreased quality of life may prolong recovery from surgery.⁷⁴⁹ Because treatment decreases the risk of local recurrence (but without changing cancer survival outcomes or your risk of distant metastasis), both risks and benefits need to be considered with your oncology team.⁷⁵⁰

Preventing Infection

Laparoscopic surgery: Fewer wound-related complications, including infections and fever, were seen with laparoscopic surgery compared to open surgery in patients with chemo-irradiated rectum tumors. The need for transfusion was also lower with laparoscopic surgery.⁷⁵¹

Taurolidine: Non-metastatic colon cancer patients undergoing surgery receiving taurolidine (ScienceDirect) showed reduced inflammation, lower risk of surgical site infection and possibly lower rates of recurrence two years after surgery.⁷⁵²

Antibiotics: Systemic ultra-short and short-term antibiotic preventive treatment (prophylaxis) before and during surgery reduces the risk of postsurgical infection. Some studies suggest giving both oral and intravenous (IV) antibiotics for greater effect. Oral, non-absorbable antibiotics may reduce risk not only of surgical site infection but also of anastomotic leak.⁷⁵³

However, prolonged antibiotic use, such as what might be required if an infection or anastomotic leak develops following surgery, may impair the function of your immune and neuroendocrine systems, increasing your risk of future infection and/or recurrence. Minimizing your risk of infection and thus reducing the need for prolonged use of antibiotics is important.

Prebiotics or probiotics: Some studies conclude that prebiotic or probiotic use around the time of surgery may reduce infections following surgery and help maintain the intestinal mucosal barrier, while other studies have shown no effect.⁷⁵⁴

Early mobilization—patient movement as much and as often as tolerable, including getting out of bed and walking—reduces the risk of pneumonia as well as surgery complications not related to infection, such as deep vein thrombosis (DVT), muscle loss and insulin resistance.⁷⁵⁵

A 2018 review concluded that these measures reduce surgical site infection after rectal surgery:⁷⁵⁶

Antibiotic prophylaxis (see below)
Preventing low body temperature (hypothermia)
Hair removal
Preventing high levels of blood glucose (hyperglycemia)

Other proposed interventions:

No fluid overload
Skin preparation with chlorhexidine
Double gloving or change of gloves and gowns before closing the fascia
Lavage of subcutaneous tissue
Silver dressing

Actions if You Develop an Infection

Pain Control

Sufficient pain control following surgery is essential to improve the quality of convalescence and speed up recovery.⁷⁵⁷ However, pain control methods vary considerably in their impact on surgery and cancer outcomes. Wise use of therapies to manage pain is extremely important to optimize both surgical and cancer outcomes.

Effectiveness of Pain Control Approaches

Drug-based Pain Management

Opioid-based intravenous patient controlled analgesia: Compared to epidural analgesia in laparoscopic surgery, opioid-based intravenous patient-controlled analgesia (IV PCA) using fentanyl showed comparable pain control, faster return of bowel function, fewer overall complications, and shorter hospital stays, plus less need of drugs to maintain blood pressure.⁷⁵⁸
Continuous surgical wound infiltration with local anesthetics used after laparoscopic colorectal surgery reported similar pain control efficacy as opioid-based IV PCA (above) in at least some patients.⁷⁵⁹
Thoracic epidural analgesia (TEA) was more effective than IV-PCA (see above) after open colorectal cancer surgery, with a better bowel function, dietary intake, patient satisfaction and early mobilization in a small trial.⁷⁶⁰
Quadratus lumborum block (QLB) was more effective analgesia following surgery than the transversus abdominis plane block.⁷⁶¹
Transabdominus plane (TAP) blocks for anesthesia as part of an enhanced recovery program with laparoscopic and robotic-assisted colorectal cancer surgery reduced the length of hospital stay, use of narcotics following surgery and the time until the patient was walking and resumed bowel function.⁷⁶²
A small pilot study investigated a multimodal pain management protocol (administered after induction anesthesia) in patients undergoing a laparoscopic resection of colorectal cancer. The protocol used a bilateral TAP block and local abdominal cavity infiltration with long-acting local anesthetic liposomal bupivacaine. Patients on this protocol required fewer opioids during surgery, had shorter stays in the post-anesthesia care unit (PACU), less pain following surgery, less use of narcotics and a shorter hospital stay compared to a group that received no block or local wound infiltration.⁷⁶³
The COX 2 selective inhibitor parecoxib—a non‐steroidal anti‐inflammatory drug—before surgical incision (compared to after incision) in colorectal cancer surgery reduced morphine use following surgery without affecting morphine-related side effects. Use before incision also reduced markers of inflammation.⁷⁶⁴

Non-drug Pain Management

Also see our Integrative Approaches and Surgery page for further research on pain management in surgery for more cancer types and other settings.

Impact of Pain Control Methods on Surgical Outcomes

Non‐steroidal Anti‐inflammatory Drugs (NSAIDs)

Acupuncture and Electroacupuncture

Movement

Opioids, Sedatives and Antidepressants

Impact of Pain Control Methods on Cancer Outcomes

Some approaches to managing pain may increase risks of suppressing your immune system and of cancer growth or recurrence.

Increased Risk of Immune Suppression and Possible Cancer Growth, Recurrence or Metastasis

Mixed Results

Opioids: The relationship of opioid drugs and cancer outcomes is difficult to separate from the effects of pain. Some evidence shows that opioid drugs—including morphine and tramadol—suppress immune responses and can promote tumor progression. However, cell studies have found that morphine both promoted and reduced processes of cell death (apoptosis). A 2014 review concluded that “further work is required to elucidate the possible impacts of morphine in cancer patients.”⁷⁸³

Preliminary evidence shows that some opioids may be used for short periods without increasing risk of cancer mortality:

A study found no differences in overall survival or disease-free survival at five years when comparing outcomes of using epidural, spinal block, or a morphine patient-controlled analgesia (PCA) for primary pain relief following surgery.⁷⁸⁴
A small study compared the opioid fentanyl used as intravenous patient-controlled analgesia (IV PCA) to a regimen of local anesthetic wound infiltration-based analgesic and tramadol. “Rescue” analgesics were used: pethidine for the opioid group and ketorolac or propacetamol for the group receiving local anesthetic. The two approaches were comparable regarding immune function (natural killer cell cytotoxicity) and complications following surgery and recurrence or metastasis within one year after surgery.⁷⁸⁵
Tramadol shows protective effects on immune function and reduced risks of recurrence and metastasis.⁷⁸⁶
One study found use of opioids vs. use of local anesthetic did not affect cancer recurrence or metastasis for one year following surgery.⁷⁸⁷

Given that opiods may disrupt immune responses and function, preventing immune disruption may be warranted with use.

Pretreatment with immunotherapy such as interferon may reduce some of the negative effects of opioids on your immune response, as suggested in animal studies.⁷⁸⁸
If opioids are indicated, lower doses may disrupt your immune system function less than larger doses.⁷⁸⁹
Substituting epidural analgesia for postoperative opioids may also improve outcomes.⁷⁹⁰

Treating pain after surgery with opioids hinders recurrence, even though opioids promote metastasis.⁷⁹¹ A 2018 review of studies concludes “there is no conclusive evidence to avoid the use of opioids with the goal of reducing the risk of recurrence in colorectal cancer.”⁷⁹²

No Increased Risk or Reduced Risk

Recovery and Remission Maintenance

See Integrative Approaches and Surgery for general information about improving your body terrain to make your body less susceptible to infection, quicker to heal wounds and/or less favorable to cancer.

Survivorship

When you have finished treatment, your cancer treatment team should develop a survivorship plan with you, including these components to help you recover and prevent recurrence:

Instructions and a schedule for follow-up visits
Testing
Guidance on lifestyle and other self-care practices

Post-Treatment Monitoring

The type of testing and monitoring used to assess your response to treatment and detect recurrence will depend on your specific cancer, treatment and risk for recurrence. A valid and reliable test to detect colorectal cancer recurrence early is still needed.

Potential Upcoming Diagnostic Tests

Talk with your doctor about whether one of these new biomarker tests is available for you. Some integrative oncologists are using these new biomarker tests already, but these tests have not been recognized by conventional oncology as a standard in clinical practice.

Eggs and Cancer

Integrative naturopathic oncologist and BCCT advisor Lise Alschuler, ND, FABNO, and her colleague Karolyn Gazella advise people with risk for colon cancer to consider limiting egg intake to fewer than five eggs a week, while choosing eggs from free-roaming, organically fed chickens. They also advise boiling or poaching eggs, as these methods do not oxidize the yolk fat.⁸⁰⁵

Colorectal Cancer

Quick Reference

Key Points

Authors

Reviewer

Colorectal Cancer: Signs, Symptoms and Screening

Integrative Care in Colorectal Cancer

Healing and Curing

Learn More

Integrative Approaches and Surgery

Clinical Practice Guidelines

Screening Guidelines

For Health Professionals: Surveillance Schedule

Colon

Rectumb

Notes and Definitions

Guidelines following Curative Treatment

Other Professional Recommendations

Examples of Integrative Approaches

Bastyr Integrative Oncology Research Center (BIORC)

Life Over Cancer System

Integrative Programs, Protocols and Medical Systems

Traditional Medicine Therapies

Integrative Therapies in Colorectal Cancer

7 Healing Practices: The Foundation

Top 5 Lifestyle Interventions following Colorectal Cancer Treatment

Bundling Practices Leads to Better Results

Eating Well

Treating the Cancer

Ask for Guidance

Managing Side Effects and Promoting Wellness

Reducing Risk

Antioxidants

B Vitamins

Calcium and Magnesium

Fiber

Optimizing Your Terrain

Beneficial Foods

Foods to Avoid

Moving More

Treating the Cancer

Managing Side Effects and Promoting Wellness

Quality of Life

Fatigue

Nausea

Sleep Disturbance

Reducing Risk

Managing Stress

Reducing Risk

Sleeping Well

Treating the Cancer

Managing Side Effects and Promoting Wellness

Reducing Risk

Improving Sleep

Creating a Healing Environment

Reducing Risk

Sharing Love and Support

Managing Side Effects and Promoting Wellness

Reducing Risk

Exploring What Matters Now

Managing Side Effects and Promoting Wellness

Beyond the 7 Healing Practices: Further Integrative Therapies

The Ultimate Guide to Cancer: DIY Research

Treating the Cancer

Avoiding Drug Interactions during Treatment

Conventional Treatments

Delaying Treatment

Factors Influencing the Success of Treatment

More on Conventional Treatments

Natural Products

Antioxidants and Cancer Outcomes

Group 1: Good clinical evidence of efficacy & safety, easy access

Group 3: Limited clinical evidence of efficacy but good safety, used in leading integrative programs

Group 4: Potential significant benefit, but either limited clinical evidence of efficacy or significant cautions

Other therapies with preclinical evidence only for treating the cancer

Group 5: Especially promising preclinical or emerging clinical evidence of efficacy and safety

Off-label, Overlooked or Novel Cancer Approaches (ONCAs)

Group A: Good clinical evidence of efficacy

Group B: Limited clinical evidence of efficacy

Group C: Promising preclinical evidence only

Rectum^b