Nutritional Support for Colon Cancer
Many nutrient deficiencies can increase risk of cancer, and biochemical variations in each person’s ability to utilize nutrients from food may lead to some harboring a nutrient deficiency despite eating well.117 Multivitamin supplements vary in forms and formulations of the nutrients they contain. All multivitamins contain folate, which is often cited as the nutrient responsible for conferring protection from colon cancer. Since several other nutrients have also been shown to lower risk, it is possible that there is synergy between nutrients that lead to protection.
Several studies indicate that multivitamin use is linked with a lower risk of colon and rectal cancers.118-120 Recently, a large pooled analysis of 13 clinical studies showed multivitamin use was associated with a 12% lower risk of colon cancer versus non-use.121 Moreover, an animal model revealed that experimental rats given a multivitamin in their drinking water were 84% less likely to developed chemical-induced aberrant crypt foci in their colons compared to their counterparts who received the chemical carcinogen without multivitamins.122
In addition, a 3-year clinical trial looked at a mixture of beta-carotene 15 mg, vitamin C 150 mg, vitamin E 75 mg, selenium 101 mcg, and calcium carbonate (1.6 grams daily) versus placebo and found that the supplement group had significantly less adenoma formation.123
The World Cancer Research Fund conducted a systematic review of studies on colorectal cancer and vitamin D intake and 25-hydroxyvitamin D status. They confirmed that higher vitamin D intake and 25-hydroxyvitamin D status were associated with reduced colon cancer risk.124
The active form of vitamin D, 1,25-dihydroxycholicalciferol has been shown to directly increase the expression of tumor suppressor cystatin D in colon cancer.125 This is of interest because both normal and malignant colon epithelial cells have the enzyme required to transform circulating 25-hydroxycholicalciferol to the active 1,25-dihydroxycholicalciferol, which is then used intracellularly to thwart the growth of the colon cancer.126
In one study, 1,179 post-menopausal women were randomized to receive calcium (1,500 mg/day), calcium with vitamin D (1,500 mg and 1,100 IU) or placebo. After four years, the incidence of cancers was less in women receiving the calcium plus vitamin D, but not the calcium alone or placebo.127 These results were in keeping with earlier data in women (46‒70 years old) showing that higher vitamin D status was associated with less risk of developing colon cancer.128
Precancerous lesions, or adenomas, are more likely to develop in those with lower circulating levels of vitamin D. A review of 12 studies of vitamin D consumption and seven studies of circulating vitamin D found that high versus low dietary intake of vitamin D reduced the risk of adenoma development by 11% and high versus low circulating levels of vitamin D reduced the risk by 30%.129
Higher circulating levels of 25-hydroxycholicalciferol [25(OH)D] are protective against colorectal cancer. For example, pooled data from the Physician’s Health Study combined with eight prospective trials showed the risk of developing colorectal cancer was lower for those with higher 25(OH)D status.130
Vitamin E is a family of eight naturally occurring compounds, four tocopherols and four tocotrienols. All forms of vitamin E are antioxidants, able to neutralize free radicals directly as well as recycle other antioxidants. Over the decades, studies have been predominantly on alpha-tocopherol, although more recent evidence suggests gamma tocopherol is the more active cancer preventative agent, particularly for colon cancer.131-133 Importantly, gamma tocopherol was more effective at inhibiting COX-2 than alpha-tocopherol, which may result in improved protection from colon cancer.134
Oxidized compounds reach the epithelial cells of the colon and rectum both from dietary sources and from normal bacterial metabolism in the colon. Alpha and gamma tocopherol have been shown to mitigate the oxidative damage, thus lowering the carcinogenic potential of these compounds.135 In an animal model, a mixture of tocopherols high in gamma tocopherol lessened colon cancer development through antioxidant, anti-inflammatory and other anti-carcinogenic mechanisms.136
Several clinical studies suggest a benefit attributable to vitamin E. In one study, intake of supplements containing alpha-tocopherol (>200 IU/d) significantly reduced the risk of colon cancer development compared to no vitamin E intake.118 In two other studies, those with the highest intakes of vitamin E had reduced risk of developing colorectal cancer as well.137,138
Tocotrienols may have their own unique anticancer mechanisms. Tocotrienols were found to increase apoptosis in colon cancer cells through modulation of the balance between pro- and anti-apoptotic mediators.139,140
Higher calcium intake appears to lower the risk of developing colorectal cancer.141,142 Calcium may protect the mucosa of the colon and rectum through binding carcinogenic bile acids,143 or through encouraging proper maturation (differentiation) of colorectal cells. Supplemental calcium, as well as vitamin D, was shown to induce favorable cellular changes in colonic cells of patients with adenomas.144
A study of 92 men and women with a history of adenoma compared the effects of calcium and vitamin D alone and together on the normal cellular turnover of the colonic epithelium. Both calcium and vitamin D, alone and together, enhanced apoptosis of normal epithelial cells.145 Interestingly, one study showed that up to five years after stopping the calcium supplementation, there was still less adenoma formation.146 Another study showed that Vitamin D and calcium taken as a supplement was associated with reduced risk, but this benefit was not found from dietary sources alone, indicating that supplementation may be necessary to attain benefit.147 Two studies in men with previous adenomas showed a risk reduction of 36% for future adenomas with supplemental calcium (1,200 mg/day for four years in one study, 2,000 mg/day for three years in the other).148
Selenium deficiency has been linked to formation of many cancers, including colorectal cancer.149 Selenium is incorporated into proteins within cells, called “selenoproteins,” involved with protecting the cells from free radical accumulation that can lead to DNA damage. Some of these proteins include glutathione peroxidases (GPx), thioredoxin reductases (TrxR), and selenoprotein P (SePP). People that form adenomas are more likely to be deficient in selenium as well as the selenoproteins that protect DNA from damage. Repletion of selenium through supplementation restored both deficiencies, presumably leading to protection from further adenoma formation.150
There have been a number of studies showing that selenium is lower in those with adenomas or colorectal cancer compared to controls.151-153 Selenium may afford even more protection in current smokers and those that have quit less than 10 years previously.154
Selenium supplementation at the time of cancer surgery can increase local immune function, an effect which may reduce recurrence.155 There may also be synergistic effects of selenium with other nutrients such as folate.156
A clinical trial of 200 mcg of selenium versus placebo found that the incidence of colorectal cancer was significantly less in those taking selenium.157
Selenium may also synergize with some cancer treatment drugs.158 In a phase I clinical trial using high doses of selenomethioninealongside the chemotherapy drug irinotecan, the authors remarked “unexpected responses and disease stabilization were noted in a highly refractory population.”159
Selenium in high amounts can be toxic and evidence suggests doses in the 200–400 mcg range are most beneficial.160
Folic acid is necessary for the synthesis of both S-adenosylmethionine (SAMe) and deoxythymidine monophosphate (dTMP). dTMP and SAMe are needed in the synthesis and function of DNA, respectively. Therefore, a deficiency of folic acid may disrupt proper DNA synthesis or function. A pooled analysis of 13 studies involving over 725,000 participants, found a 2% risk reduction for every 100 mcg/day increase of total folic acid intake.28 In a large population study, those taking the highest amount of folate from diet and supplements (>900 mcg/day) had a 30% reduced risk of developing colon cancer versus those with the lowest consumption (<200 mcg/day).161
Alcohol consumption increases the risk of colon cancers, and evidence suggests this may be potentiated by polymorphisms in genes that produce enzymes involved in folate metabolism.162 Maintaining adequate levels of folate, and its co-nutrient methionine, may offer protection from colon adenoma development, particularly in those consuming alcohol or those with genetic polymorphisms in folate metabolism.163
Green Coffee and Chlorogenic Acids
Greater coffee consumption has been linked with a lower rate of a variety of cancers, including colon cancer.164,165
Coffee contains powerful antioxidant compounds, called chlorogenic acids, which have been shown to exert several potentially chemopreventive effects, including favorably modulating glucose metabolism, and quelling inflammation.166,167 In fact, a recent study found that chlorogenic acids were able to interfere with a variety of cellular processes that drive colon cancer metastasis, including NF-kB signaling.168
However, the roasting process used to prepare conventional coffee beverages destroys the majority of these beneficial chlorogenic acids. Therefore, drinking coffee is an inefficient means of obtaining these bioactive compounds.
Recent scientific innovation has led to the availability green coffee bean extract standardized to 50% chlorogenic acids. Supplementation with green coffee bean extract is a viable option for obtaining robust quantities of bioactive chlorogenic acids.
Consumption of garlic has been linked with lower colon cancer risk.169 Garlic has been shown to reduce the carcinogenic potential of compounds such as nitrosamines, as well as exert anti-proliferative effects.170,171 Components that may be responsible for the cancer protective effects of garlic include organosulfur compounds and flavonoids.
There are many mechanisms that can explain how garlic reduces carcinogenesis in the colon and rectum.
- Inhibition of cell growth and proliferation directly
- Inhibition of new blood vessel growth
- Increased cell death (apoptosis)
- Increased detoxification of carcinogens
- Suppression of carcinogen activating enzymes
- Inhibition of cyclooxygenase-2 (thereby inhibition of inflammation)
- Antioxidant action, squelching free radicals in the bowel172
One clinical trial showed that supplementing with aged garlic extract reduced the formation of pre-cancerous adenomas in patients with a history of adenomas.173
Like garlic, ginger has been a mainstay of traditional medicine for more than 2,500 years. Ginger’s multiple chemopreventive benefits have been reported in a wide range of experimental models.174 Key compounds in ginger and its extracts limit the oxidative damage to cells caused by free radicals. They also lower levels of signaling molecules called cytokines, specifically those that provoke an inflammatory response. This dual mode of action may inhibit initiation of carcinogenesis and limit expansion of existing malignancies.175,176 Some ginger components also increase the activity of vital enzymes that detoxify carcinogens present in the body.177,178
Indian researchers provided direct evidence of ginger’s chemopreventive power in rats with chemically induced colon cancers in two recent studies.179,180 After injection with a potent carcinogen, animals were either supplemented with ginger or given normal diets. In both studies the incidence of cancers and the number of individual tumors was significantly reduced in the supplemented groups. The first study also detected lower levels of oxidative agents and higher levels of natural antioxidants in supplemented animals, while the second study further showed a decrease in the activity of bacterial enzymes that release intestinal toxins and damage the colon’s natural protective mucous layer.
In recent clinical trial, 30 healthy subjects consumed 2 grams of ginger or a placebo each day for 28 days. Colon biopsies were taken at baseline and at day 28 and assessed for levels of inflammatory markers. The subjects that received ginger displayed significantly lower levels of PGE-2 and 5-HETE, two inflammatory fatty acid metabolites, in their tissue samples than those who received a placebo.181 These findings are encouraging due to the role of inflammation in driving colon cancer growth.
Modified Citrus Pectin
Modified Citrus Pectin (MCP) is a type of soluble dietary fiber derived from citrus fruits that has been modified by pH and heat to form smaller units of absorbable galactose residues that are able to bind to cancer cells. Specifically, MCP binds to galectin-3, a protein expressed by cancer cells that is involved in cell to cell adhesion, survival and spread to distant organs (metastasis).182,183 Nullifying the effects of galectin-3 by finding agents to bind to it is one means of inhibiting these pro-cancerous mechanisms.184,185 MCP has been shown to effectively bind galectin-3 and inhibit growth and metastasis of various cancers,186 including colon cancer.187
Interfering with galectin-3 and preventing metastasis is particularly important in colorectal cancer, where spread to the liver means a much worse prognosis than limited or local disease. Galectin-3 levels appear to be increased in colon cancer, and are associated with advanced disease stage,188,189 confirming that galectin-3 is an important molecule in the growth and spread of colon cancers.
Additional discussion on the role of MCP in combatting cancer metastasis can be found in the Life Extension Magazine article entitled “ Fighting Cancer Metastasis and Heavy Metal Toxicities With Modified Citrus Pectin”.
Curcumin is derived from the spice turmeric (Curcuma longa), an ancient spice used throughout Asia. Cultures in which diets high in turmeric are consumed have much lower rates of colon cancer than Western cultures.108 Curcumin is a powerful anti-inflammatory compound that acts on NF-kB, a proinflammatory mediator that influences hundreds of genes involved in the growth and spread of cancer. In addition, curcumin regulates tumor suppressor pathways and triggers mitochondrial-mediated death in cancer cells.190,191
Despite aggressive surgical care and chemotherapy, nearly 50% of people with colorectal cancers develop recurrent tumors.192 This may be due in part to the survival of dangerous colon cancer stem cells that resist conventional chemotherapy and act as “seeds” for subsequent cancers.193 There is evidence that combining curcumin with FOLFOX, the first line chemotherapy drug combination of 5-fluorouricil, leucovorin and oxaliplatin, eliminates the persistent pool of colon cancer stem cells,194 and potentiates the lethality of FOLFOX on cancer cells.195
Finally, curcumin interferes with tumor invasiveness and blocks molecules that would otherwise open pathways to penetration of tissue.1 It also helps to starve tumors of their vital blood supply and it can oppose many of the processes that permit metastases to spread.196 These multi-targeted actions are central to curcumin’s capacity to block multiple forms of cancer before they manifest.197
Curcumin also creates a gastrointestinal environment more favorable to optimal colon health by reducing levels of so-called secondary bile acids, natural secretions that contribute to colon cancer risk.198 That has a direct effect, inhibiting proliferation of cancer cells and further reducing their production.199
A novel feature of curcumin is its ability to bind to and activate vitamin D receptors (VDR) in colon cells.200 Binding to VDR elicits a host of anti-proliferative and anti-inflammatory actions.
Curcumin given to patients undergoing treatment for colon cancer led to weight gain, decreased circulating inflammatory mediator tumor necrosis factor (TNF)-alpha, and increased apoptosis.201
Omega-3 Fatty Acids
There is a substantial amount of experimental, population-based studies and clinical trials showing that risk of colorectal cancer is reduced with higher intakes of omega-3 fatty acids.202-208
EPA (2 grams/d for three months) reduced crypt cell proliferation and promoted proper apoptosis of colonic epithelial cells in patients with a history of colonic adenomas.209 Separately, a large population study of physicians found that those who consumed fish oil supplements during a 10-year period had a 35% reduction in the risk of developing colon cancer.210
Omega-3 fatty acids may prevent colorectal cancer through supporting normal turnover of the epithelial cells by encouraging apoptosis.206 Fish oils reduce the pro-tumor effects of many molecules involved in the growth and spread of colon cancer, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), platelet-derived endothelial cell growth factor (PDECGF), cyclo-oxygenase 2 (COX-2), prostaglandin-E2 (PGE2), nitric oxide, NF-kB, matrix metalloproteinases and beta-catenin.211
DHA, an omega-3 fatty acid found in fish oil, disrupts cell signaling in colon cancer and is synergistic with butyrate in inducing apoptosis.212,213
Fish oil (2.5 grams/day) normalized abnormal rectal proliferation patterns in patients with a history of adenomas, and this is thought to be through lessening the availability of the inflammatory omega-6 fatty acid arachidonic acid and modifying vitamin E availability.214,215
Chemotherapies induce cell death by inducing DNA damage in quickly dividing cells, tipping the death/survival pathways toward cellular self-destruction (apoptosis). Experiments have shown EPA and DHA can make cancer cells more vulnerable to damage from chemotherapy and radiation, thus encouraging the cells to turn on cell death pathways in lieu of repair pathways.216-218 Eventual resistance of colon cancer cells to the cytotoxic effects of chemotherapy may also be lessened with EPA/DHA.219
Polysaccharide K (PSK)
PSK is a mushroom polysaccharide complex used more commonly in other countries such as Japan and Australia for immune support in cancer care. Pure PSK cannot be obtained in the United States, but the mushroom Trametes versicolor (formerly called Coriolus versicolor) is high in this polysaccharide and is often substituted. Many mushrooms have some immune enhancing properties, but PSK can also suppress activation of NF-kB, therefore reducing the expression of hundreds of pro-cancerous genes.220
A review of three clinical trials in patients who had surgery and chemotherapy for their colon cancer showed that overall survival was improved by 29% with the addition of PSK.221
A group of colon cancer patients were randomized to receive chemotherapy alone or chemotherapy plus PSK, which was taken for two years. The group receiving PSK had an exceptional 10-year survival of 82%. The group receiving chemotherapy alone had a 10-year survival of only 51%.222 In a similar trial reported in the British Journal of Cancer in 2004, colon cancer patients received chemotherapy alone or combined with PSK (3 grams per day) for two years. In the group with stage 3 colon cancer, the five-year survival was 75% in the PSK group. This compared to a five-year survival of only 46% in the group receiving chemotherapy alone.223
Sulforaphane is a compound that is found in cruciferous vegetables, like broccoli and kale. It improves the elimination of toxic substances by the liver. It also may have a more direct role in thwarting the growth of cancers, including colorectal cancer, through re-activation of tumor suppressor genes that were formerly silenced.224,225
Sulforaphane inhibited the formation of colon tumors in an animal model.226 It is also able to induce apoptosis in colon cancer cells with impaired apoptosis capability.227
Sulforaphane appears to protect normal colon cells while encouraging self-destruction of colon cancer cells.228 When added to oxaliplatin, sulforaphane improved the ability of the drug to kill colon cancer cells.229
In one study, sulforaphane was synergistic with indole-3-carbinol, another compound from cruciferous vegetables. Together the compounds resulted in greater toxicity to colon cancer cells than either compound alone.230
Resveratrol is a polyphenol found in grapes, peanuts and mulberries. Resveratrol suppresses colitis and colitis associated colon cancer in mice.231 Grape powder and resveratrol inhibited the carcinogenic Wnt pathway in normal colonic mucosa.232,233 Resveratrol also inhibits the COX-2 enzyme, suppressing inflammation.234 Resveratrol may synergize with butyrate in the colon as well.235
Resveratrol has been shown to lessen aberrant crypt formation236,237 and adenoma formation238 as well as induce apoptosis of colon cancer cells.239,240
A small study of twenty patients scheduled for colon resection to remove malignancy showed that a dose of 0.5‒1.0 grams/day for eight days prior to surgery resulted in adequate levels of resveratrol in the tumors to have biological effects. This was particularly true for tumors on the right (proximal) side.241
Resveratrol may also increase the sensitivity of colon cancer cells to the killing effects of chemotherapy.242
Green Tea Extract
Green tea contains potent antioxidants known as catechins, the most well studied of which is epigallocatechin-3-gallate (EGCG), which has been found to inhibit carcinogenesis in various cancers, including colorectal cancers.243-245
Green tea extract is well established to have anticancer actions on growth, survival, angiogenesis and metastatic processes of cancer cells246,247 and favorable effects on immune function.248 Green tea has also been shown to reduce the carcinogenicity of nitrosamines, carcinogenic compounds from cooked meats.249
A meta-analysis of consumption of green tea across populations found that those consuming the highest levels of green tea had an 18% lower risk of developing colorectal cancer compared to those consuming the lowest amounts.250 In a clinical study, green tea extract (equivalent of >10 cups/day, or about 150 mg EGCG) lessened adenoma formation, both number and severity, in those with a prior history of adenomas.251
Milk thistle (Silybum marianum) contains silibinin and silymarin, flavonoid compounds shown to have numerous anticancer effects. Milk thistle is generally used to improve the break down and elimination of chemicals and toxins, so it is not surprising that silymarin was able to prevent chemically induced colon cancer in mice.252 In another animal study, silymarin, along with quercetin, curcumin, rutin, all independently reduced aberrant crypt formation, an early process in colon cancer formation.253 Silymarin also inhibits angiogenesis,254 a necessary process for tumor growth.
Silibinin has been shown to inhibit colorectal carcinogenesis directly.255 Silibinin blocks proliferation, reduces new blood vessel growth and induces cell death (apoptosis) of colorectal cancer cells.256-259 It may achieve some of these anti-tumor effects through disruption of signaling pathways within cancer cells as well as by blocking activation of NF-kB.260
Quercetin belongs to a class of potent antioxidants called flavonoids. These are what give apples their color. Onions, garlic, tea, red grapes, berries, broccoli, and leafy greens are also rich sources of quercetin.
It’s well known to nutritional scientists as a potent free radical-scavenger.261 Quercetin also happens to possess a singular cancer-fighting feature: it can prevent cancer caused by chemicals. Its unique molecular structure enables it to block receptors on the cell surface that interact with carcinogenic chemical compounds. This makes it a perfect anticancer agent for the colon, where carcinogenic chemicals tend to accumulate.261
Researchers in Greece have also discovered that quercetin dramatically suppresses one particular cancer-causing gene in colon cells. This makes quercetin supplementation an ideal form of early prevention for individuals with a family history of colon cancer.262
Dutch scientists uncovered even more evidence of its cancer-preventive power at the genetic level. In an animal study, quercetin reduced “cancer gene” activity and increased “tumor-suppressor gene” activity in colon cells after 11 weeks.263
In yet another promising animal study, scientists in South Carolina were able to halt the development of aberrant crypts. Cancer-prone rats fed a diet high in quercetin34 underwent a four-fold reduction in the number of aberrant crypts compared to a control group. Similar research has yielded additional evidence of quercetin’s capacity to reduce emerging aberrant crypts—a vital first step in preventing colon cancer from developing at all.264
In 2006, scientists at the Cleveland Clinic evaluated patients suffering from familial adenomatous polyposis. They discovered that a combination of curcumin and quercetin could cause these growths to diminish substantially. The researchers supplemented the patients with 480 mg of curcumin and 20 mg of quercetin orally, three times a day, for six months. Every single patient experienced a remarkable decrease in polyp numbers and size, with average reductions of 60% and 51%, respectively.265
NAC is a slightly modified version of the sulfur-containing amino acid cysteine.
When taken internally, NAC replenishes intracellular levels of the natural antioxidant glutathione (GSH), helping to restore cells’ ability to avoid damage from reactive oxygen species. NAC suppresses the NF-kB, which in turn prevents activation of multiple inflammatory mediators.266,267 NAC also regulates the gene for COX-2, the enzyme that produces pain- and inflammation-inducing prostaglandins in a wide array of chronic conditions.268
NAC (800 mg/day) lessened the rate of proliferation of the cells in the colonic crypts in patients with a history of adenomatous polyps.269 This is in keeping with a study that showed that those with a history of polyps had a 40% reduction in recurrence of their polyps using 600 mg of NAC daily.270
NOTE: This protocol should not be used in isolation. Individuals with colorectal cancer should also review the content in other Life Extension cancer protocols, including:
Disclaimer and Safety Information
This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the treatments discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.
The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. The publisher has not performed independent verification of the data contained herein, and expressly disclaim responsibility for any error in literature.