Colon Cancer Prevention Clinical Trial
Official title:
Exploring the Effects of a High Chlorophyll Dietary Intervention to Reduce Colon Cancer Risk in Adults: The Meat and Three Greens Feasibility Trial
Colon cancer is the third most common cancer in men and women and over 70% of cases are
preventable. A western diet, characterized by low vegetable and high red and processed meat
intake, indisputably increases colon cancer risk. Heme, which gives red meat its color, is
highly reactive, induces hyperproliferation and promotes DNA damage in the colon to a greater
degree than any other red meat-associated carcinogen. Preclinical models indicate dietary
chlorophyll, which gives green leafy vegetables their color, binds and stabilizes heme in the
lumen, preventing genotoxicity. Additionally, data from our randomized controlled weight loss
trial indicate increasing red meat consumption has deleterious effects on the gut microbiome,
which is also implicated in colon cancer etiology. Because heme-containing foods are the
richest sources of bioavailable iron and several other vitamins and minerals, mitigating
their potential risks may be more beneficial than eliminating meat, poultry, fish and seafood
in their entirety from the diet for risk reduction.
This feasibility study will begin to explore the research question: Will adding
chlorophyll-rich green leafy vegetables to the diet prevent the deleterious effects of
heme-rich red meat on the human host and microbiome? The investigators will randomly assign
50 adults at increased risk of colorectal adenoma to a block randomized crossover study with
two 4-week dietary regimens in which: 1) participants will be provided with frozen green
leafy vegetables and counseled to consume a high chlorophyll diet including 1 cup per day of
cooked green leafy vegetables and normal meat (high heme) consumption; or 2) continue their
normal high heme, low chlorophyll diet (control). A 4-week washout period encouraging
habitual diet will be employed between the intervention periods and data will be collected at
all four time points.
This study is critical in translating preclinical findings and has the potential to open the
door to new knowledge and standards of care in colon cancer prevention. This study is a
required step to aid in the design of a larger RCT to determine whether increased green leafy
vegetable consumption mitigates the negative effects of red meat on DNA damage, inflammatory
cytokines and gut microbe composition. This could lead to equally beneficial dietary guidance
for colon health that might be more easily attained by the general public through addition,
rather than omission of specific foods.
Fifty thousand cases of colon and rectal cancer (CRC) could be prevented each year through
screening, increased exercise and improved diet. Obesity alone increases risk of CRC by 33%
and is associated with increased CRC mortality. Red and processed meat consumption is
associated with increased CRC risk, most often in the context of dietary patterns, which
juxtapose "Western" and "prudent" diets. A recent meta-analysis of 24 case control studies
and 11 prospective cohort studies (n=1,295,063 men and women) found an 18% reduction in risk
for colon cancer in the groups consuming the highest levels of cruciferous and green leafy
vegetables. Risk reduction with high green leafy vegetable consumption remained significant
regardless of whether pooled studies controlled for meat and/or total energy intake.
Heme-induced genotoxicity of the colon is prevented by chlorophyll in rodent models; an
important finding that has not been tested in clinical trials though is supported by
epidemiological observation.
This trial utilizes a crossover design to assess the feasibility of a dietary intervention in
adults at increased risk of CRC. The overall intent of this line of research is to elucidate
a CRC risk-reducing dietary pattern that is accessible to the general public. Therefore,
obese, meat-eating participants will be randomized to an intervention and control diet: 1)
high chlorophyll (green leafy vegetables) and high heme (normal meat) consumption; and 2)
habitual high heme, low chlorophyll diet (control). During the intervention periods, all
participants will receive individual dietary counseling from a registered dietitian two days
per week to reinforce daily consumption goals based on the amounts of chlorophyll and heme in
various foods. This study translates preclinical models, utilizes an appropriate at-risk
population, and if feasible, has the potential to be tested for efficacy for the reduction of
colon cancer risk.
Participants will be recruited through the Auburn University Pharmaceutical Care Clinic and
throughout the Auburn community. After completing all baseline procedures, participants will
be block randomized by gender due to potential differences in fecal microbiome. All
participants will receive the intervention; the order in which it is received will be
randomly generated. For the high chlorophyll study arm, a goal of 1 cup cooked dark leafy
green vegetables will be prescribed, and participants will be instructed to consume at least
½ cup cooked dark green leafy vegetables during the same meal they consume red meat. The high
chlorophyll group will also receive a variety of frozen dark green leafy vegetables,
including, spinach, kale, collards, mustard greens, and turnip greens. Frozen vegetables are
provided because flash-freezing minimizes nutrient loss and prevents chlorophyll degradation.
Though the chlorophyll content varies between these species, it is exponentially higher than
other green vegetables in the brassica family. Participants will be instructed to consume
cooked vegetables, rather than raw, to increase the bioavailability of chlorophyll and reduce
the volume of the needed amount of vegetable.
After each 4-week period, participants will complete questionnaires, return unused frozen
vegetables (which will be tracked), provide a stool sample, and undergo phlebotomy. Study
staff will obtain two 24-hour dietary recalls on non-consecutive days. Participants will be
provided with an additional fecal collection kit for the sample that will be obtained prior
to the next dietary arm assignment.
The behavioral framework of this intervention will utilize Social Cognitive Theory as the
basis for behavior change in each intervention arm. Participants will increase self-efficacy
of dietary adherence by setting goals and logging daily food intake (self-monitoring), which
will be assessed in twice weekly counseling sessions with a registered dietitian.
;
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