Exploring the Effects of a High Chlorophyll Dietary Intervention to Reduce Colon Cancer Risk in Adults: The Meat and Three Greens Feasibility Trial

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.